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Sample records for extrapleural fat hypertrophy

  1. Extrapleural Inner Thoracic Wall Lesions: Multidetector CT Findings

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    Kim, Seung Soo; Kim, Young Tong; Jou, Sung Shik [Soonchunhyang University, Cheonan Hospital, Cheonan (Korea, Republic of)

    2010-06-15

    The extrapleural space is external to the parietal pleura in the thorax. The structures within and adjacent to this region include the fat pad, endothoracic fascia, intercostal muscles, connective tissue, nerves, vessels, and ribs. Further, the space is divided into the inner and outer thoracic wall by the innermost intercostal muscle. Extrapleural lesions in the inner thoracic wall are classified as air-containing lesions, fat-containing lesions, and soft tissue-containing lesions according on their main component. Air-containing lesions include extrapleural air from direct chest trauma and extrapleural extension from pneumomediastinum. Prominent extrapleural fat is seen in decreased lung volume conditions, and can also be seen in normal individuals. Soft tissue-containing lesions include extrapleural extensions from a pleural or chest wall infection as well as tumors and extrapleural hematoma. We classify extrapleural lesions in the inner thoracic wall and illustrate their imaging findings

  2. Left ventricular hypertrophy and obesity: only a matter of fat?

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    Murdolo, Giuseppe; Angeli, Fabio; Reboldi, Gianpaolo; Di Giacomo, Letizia; Aita, Adolfo; Bartolini, Claudia; Vedecchia, Paolo

    2015-03-01

    Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the absence of hypertension, adiposity induces structural and functional changes in the heart through hemodynamic and non hemodynamic factors. In the "obese" heart, besides the growth of cardiomyocytes, interstitial fat infiltration and triglyceride accumulation in the contractile elements importantly contribute to left-ventricular mass (LVM) accrual, hypertrophy (LVH) and geometric pattern. In harmony with this, the likelihood of LVH is greater in either obese normotensive or hypertensive individuals than in their non-obese counterparts. Interestingly, recent observations highlight the increasing prevalence of the "concentric" (ie, combined remodeling and hypertrophy), rather than "eccentric" pattern of LV geometry in obesity. Nonetheless, obesity is linked with lack of decrease, or even increase, of LVM over time, independently of blood pressure control and hypertensive treatment. Although obesity-related LV changes result in progressive systolic and diastolic heart failure, the assessment of LVM and LVH in obese individuals still remains a difficult task. In this scenario, it is tempting to speculate that therapeutic interventions for reversal of LVH in obesity should either overcome the "non-hemodynamic" factors or reduce the hemodynamic load. Indeed, weight loss, either achieved by lifestyle changes or bariatric procedures, decreases LVM and improves LV function regardless of blood pressure status. These and other mechanistic insights are discussed in this review, which focuses on "adipose dysfunction" as potential instigator of, and putative therapeutic target for, LVH regression in the setting of obesity.

  3. Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women.

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    Veilleux, Alain; Caron-Jobin, Maude; Noël, Suzanne; Laberge, Philippe Y; Tchernof, André

    2011-05-01

    We assessed whether subcutaneous and omental adipocyte hypertrophy are related to metabolic alterations independent of body composition and fat distribution in women. Mean adipocyte diameter of paired subcutaneous and omental adipose tissue samples was obtained in lean to obese women. Linear regression models predicting adipocyte size in both adipose tissue depots were computed using body composition and fat distribution measures (n = 150). In a given depot, women with larger adipocytes than predicted by the regression were considered as having adipocyte hypertrophy, whereas women with smaller adipocytes than predicted were considered as having adipocyte hyperplasia. Women characterized by omental adipocyte hypertrophy had higher plasma and VLDL triglyceride levels as well as a higher total-to-HDL cholesterol ratio compared with women characterized by omental adipocyte hyperplasia (P women characterized by subcutaneous adipocyte hypertrophy or hyperplasia showed a similar lipid profile. In logistic regression analyses, a 10% enlargement of omental adipocytes increased the risk of hypertriglyceridemia (adjusted odds ratio [OR] 4.06, P independent of body composition and fat distribution measures. A 10% increase in visceral adipocyte number also raised the risk of hypertriglyceridemia (adjusted OR 1.55, P independent of body composition and fat distribution in women.

  4. Effects of Temperature and Adult Diet on Development of Hypertrophied Fat Body in Prediapausing Boll Weevil (Coleoptera Curculionidae)

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    Terence L. Wagner; Eric J. Villavaso

    1999-01-01

    This study examines the effects of temperature and adult diet on the development of hypertrophied fat bodies in prediapausing adult boll weevils, Anthonomus grandis grandis Boheman. Simulation models derived from this work are used to estimate the minimal ages at which male and female boll weevils exhibit diapause morphology, based on conditions...

  5. Fat Mass Reduction With Adipocyte Hypertrophy and Insulin Resistance in Heterozygous PPARγ Mutant Rats.

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    Gumbilai, Valentino; Ebihara, Ken; Aizawa-Abe, Megumi; Ebihara, Chihiro; Zhao, Mingming; Yamamoto, Yuji; Mashimo, Tomoji; Hosoda, Kiminori; Serikawa, Tadao; Nakao, Kazuwa

    2016-10-01

    Agonist-induced activation of peroxisome proliferator-activated receptor-γ (PPARγ) stimulates adipocyte differentiation and insulin sensitivity. Patients with heterozygous PPARγ dominant-negative mutation develop partial lipodystrophy and insulin resistance. Inconsistent with this evidence in humans, it was reported that heterozygous PPARγ knockout mice have increased insulin sensitivity and that mice with heterozygous PPARγ dominant-negative mutation have normal insulin sensitivity and improved glucose tolerance. In the context of the interspecies intranslatability of PPARγ-related findings, we generated a PPARγ mutant rat with a loss-of-function mutation (Pparg(mkyo)) without dominant-negative activity by using the ENU (N-ethyl-N-nitrosourea) mutagenesis method. Heterozygous Pparg(mkyo/+) rats showed reduced fat mass with adipocyte hypertrophy and insulin resistance, which were highly predictable from known actions of PPARγ agonists and phenotypes of patients with the PPARγ mutation. This report is the first in our knowledge to clearly demonstrate that both alleles of PPARγ are required for normal adipocyte development and insulin sensitivity in vivo. Furthermore, the study indicates that PPARγ regulates mainly adipocyte number rather than adipocyte size in vivo. The choice of appropriate species as experimental models is critical, especially for the study of PPARγ. © 2016 by the American Diabetes Association.

  6. Restoration of Circulating MFGE8 (Milk Fat Globule-EGF Factor 8) Attenuates Cardiac Hypertrophy Through Inhibition of Akt Pathway.

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    Deng, Ke-Qiong; Li, Jing; She, Zhi-Gang; Gong, Jun; Cheng, Wen-Lin; Gong, Fu-Han; Zhu, Xue-Yong; Zhang, Yan; Wang, Zhihua; Li, Hongliang

    2017-10-01

    Cardiac hypertrophy occurs in response to numerous stimuli like neurohumoral stress, pressure overload, infection, and injury, and leads to heart failure. Mfge8 (milk fat globule-EGF factor 8) is a secreted protein involved in various human diseases, but its regulation and function during cardiac hypertrophy remain unexplored. Here, we found that circulating MFGE8 levels declined significantly in failing hearts from patients with dilated cardiomyopathy. Correlation analyses revealed that circulating MFGE8 levels were negatively correlated with the severity of cardiac dysfunction and remodeling in affected patients. Deleting Mfge8 in mice maintained normal heart function at basal level but substantially exacerbated the hypertrophic enlargement of cardiomyocytes, reprogramming of pathological genes, contractile dysfunction, and myocardial fibrosis after aortic banding surgery. In contrast, cardiac-specific Mfge8 overexpression in transgenic mice significantly blunted aortic banding-induced cardiac hypertrophy. Whereas MAPK (mitogen-activated protein kinase) pathways were unaffected in either Mfge8 -knockout or Mfge8 -overexpressing mice, the activated Akt/PKB (protein kinase B)-Gsk-3β (glycogen synthase kinase-3β)/mTOR (mammalian target of rapamycin) pathway after aortic banding was significantly potentiated by Mfge8 deficiency but suppressed by Mfge8 overexpression. Inhibition of Akt with MK-2206 blocked the prohypertrophic effects of Mfge8 deficiency in angiotensin II-treated neonatal rat cardiomyocytes. Finally, administering a recombinant human MFGE8 in mice in vivo alleviated cardiac hypertrophy induced by aortic banding. Our findings indicate that Mfge8 is an endogenous negative regulator of pathological cardiac hypertrophy and may, thus, have potential both as a novel biomarker and as a therapeutic target for treatment of cardiac hypertrophy. © 2017 American Heart Association, Inc.

  7. Postmortem noninvasive virtual autopsy: extrapleural hemorrhage after blunt thoracic trauma.

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    Bolliger, Stephan A; Thali, Michael J; Aghayev, Emin; Jackowski, Christian; Vock, Peter; Dirnhofer, Richard; Christe, Andreas

    2007-03-01

    A 19-year-old man speeding recklessly along a highway caused a left-frontal crash with another car. After his vehicle came to a standstill, he climbed out of the wreck and crawled across the tarmac to the other side of the road, where he died several minutes after the accident and before the arrival of an ambulance. Postmortem multislice computed tomography (MSCT) demonstrated fractures of the first, second, and third ribs and scapula on the left, an extrapleural hemorrhage in the apical region of the left thorax, as well as a large amount of blood in the left thoracic cavity. These radiologic findings were indicative of a delayed rupture of a traumatic extrapleural hematoma into the pleural space. A traditional autopsy confirmed the very rare diagnosis of a traumatic extrapleural hemorrhage with a delayed rupture.

  8. Current Treatment of Mesothelioma: Extrapleural Pneumonectomy Versus Pleurectomy/Decortication.

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    Wolf, Andrea S; Flores, Raja M

    2016-08-01

    The role of surgical resection in malignant pleural mesothelioma (MPM) is based on the principle of macroscopic resection of a solid tumor with adjuvant therapy to treat micrometastatic disease. Extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) have been developed in this context. Cancer-directed surgery for MPM is associated with a 5-year survival rate of 15%. Evidence indicates that P/D is better tolerated by patients and suggests survival is no worse when compared with EPP. Although EPP is still performed in highly selected cases, the authors advocate radical P/D whenever possible for patients with MPM. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Extrapleural pneumonectomy (EPP) vs. pleurectomy decortication (P/D).

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    Batirel, Hasan Fevzi

    2017-06-01

    Surgical techniques for treatment of malignant pleural mesothelioma (MPM) have improved over the decades. The main surgical principle was accepted as macroscopic complete resection. This principle was achieved with extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (P/D). Mortality and morbidity are higher following EPP with supraventricular arrhythmias, pulmonary embolism, bronchopleural fistula and pulmonary failure being the most common, while prolonged air leak is frequent following P/D. Completion of multimodality treatment was also shown to be a prognostic factor. Many different neoadjuvant and adjuvant protocols were applied with limited effect on prognosis. While locoregional recurrence is more common following P/D, EPP patients typically recur in contralateral hemithorax and abdomen. Hemithoracic radiation following EPP was the only effective technique shown to decrease locoregional recurrence. However, neither surgical technique (EPP vs. P/D), nor types of multimodality treatment protocols were found to be prognostic in MPM. Epithelioid histology, metastasis to extrapleural lymph nodes and completion of multimodality treatment were prognostic in most of the series. In conclusion, based on the current evidence, the choice of a less morbid and mortal procedure (P/D) seems to be the logical choice in the treatment of MPM.

  10. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy.

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    Diniz, Gabriela Placoná; Huang, Zhan-Peng; Liu, Jianming; Chen, Jinghai; Ding, Jian; Fonseca, Renata Inzinna; Barreto-Chaves, Maria Luiza; Donato, Jose; Hu, Xiaoyun; Wang, Da-Zhi

    2017-12-15

    Obesity is associated with development of diverse diseases, including cardiovascular diseases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously, we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In the present study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high-fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alter HF diet induced cardiac hypertrophy or fibrosis in the heart. Our study therefore establishes miR-22 as an important regulator of dyslipidemia and suggests it may serve as a potential candidate in the treatment of dyslipidemia associated with obesity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits.

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    Rodríguez-Castelán, J; Méndez-Tepepa, M; Carrillo-Portillo, Y; Anaya-Hernández, A; Rodríguez-Antolín, J; Zambrano, E; Castelán, F; Cuevas-Romero, E

    2017-01-01

    Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

  12. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

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    J. Rodríguez-Castelán

    2017-01-01

    Full Text Available Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT. Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C. In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

  13. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

    Science.gov (United States)

    Rodríguez-Castelán, J.; Méndez-Tepepa, M.; Carrillo-Portillo, Y.; Anaya-Hernández, A.; Zambrano, E.

    2017-01-01

    Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood. PMID:28133606

  14. Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice.

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    Allen, London; Ramalingam, Latha; Menikdiwela, Kalhara; Scoggin, Shane; Shen, Chwan-Li; Tomison, Michael D; Kaur, Gurvinder; Dufour, Jannette M; Chung, Eunhee; Kalupahana, Nishan S; Moustaid-Moussa, Naima

    2017-10-01

    Inflammation is a major underlying cause for obesity-associated metabolic diseases. Hence, anti-inflammatory dietary components may improve obesity-related disorders. We hypothesized that delta-tocotrienol (δT3), a member of the vitamin E family, reduces adiposity, insulin resistance and hepatic triglycerides through its anti-inflammatory properties. To test this hypothesis, C57BL/6J male mice were fed a high-fat diet (HF) with or without supplementation of δT3 (HF+δT3) at 400 mg/kg and 1600 mg/kg for 14 weeks, and they were compared to mice fed a low-fat diet (LF) or HF supplemented with metformin as an antidiabetic control. Glucose tolerance tests were administered 2 weeks prior to the end of treatments. Histology, quantitative polymerase chain reaction and protein analyses were performed to assess inflammation and fatty acid metabolism in adipose and liver tissues. Significant improvements in glucose tolerance, and reduced hepatic steatosis and serum triglycerides were observed in δT3-supplemented groups compared to the HF group. Body and fat pad weights were not significantly reduced in HF+δT3 groups; however, we observed smaller fat cell size and reduced macrophage infiltration in their adipose tissues compared to other groups. These changes were at least in part mechanistically explained by a reduction of mRNA and protein expression of proinflammatory adipokines and increased expression of anti-inflammatory adipokines in HF+δT3 mice. Moreover, δT3 dose-dependently increased markers of fatty acid oxidation and reduced markers of fatty acid synthesis in adipose tissue and liver. In conclusion, our studies suggest that δT3 may promote metabolically healthy obesity by reducing fat cell hypertrophy and decreasing inflammation in both liver and adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet.

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    Hosoo, Shingo; Koyama, Masahiro; Watanabe, Akira; Ishida, Ryuya; Hirata, Tetsuya; Yamaguchi, Yasuyo; Yamasaki, Hiroo; Wada, Keiji; Higashi, Yukihito; Nakamura, Kozo

    2017-06-01

    Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). To explore the effects of chronic administration of ELE on body weight, blood pressure and aortic media thickness, 7-week-old male Wistar-Kyoto (WKY) rats were orally administered a normal diet, a 30% HFD, or a 5% ELE plus HFD ad libitum for 10 weeks. The HFD treatment caused mild obesity and hypertension in the normotensive rats, while rats receiving both ELE and the HFD had significantly lower body weights, less visceral and perirenal fat, lower blood pressure and thinner aortic media than the control rats receiving the HFD only. The plasma adiponectin/leptin ratio also improved in ELE-treated rats. Although plasma leptin levels were elevated in all HFD rats, adiponectin levels increased only in the ELE-treated rats. Anti-hypertensive and anti-obesity effects may be caused by the geniposidic acid (GEA) and/or asperuloside present in ELE. These findings suggest that chronic ELE administration prevents aortic media hypertrophy in early-stage obesity with hypertension. Long-term administration of ELE might inhibit the development of arteriosclerosis.

  16. MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway.

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    Kuwabara, Yasuhide; Horie, Takahiro; Baba, Osamu; Watanabe, Shin; Nishiga, Masataka; Usami, Shunsuke; Izuhara, Masayasu; Nakao, Tetsushi; Nishino, Tomohiro; Otsu, Kinya; Kita, Toru; Kimura, Takeshi; Ono, Koh

    2015-01-16

    In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated. To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM. C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in neonatal rat cardiac myocytes and Cab39 overexpression rescued the lipotoxicity. To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in cardiomyocyte-specific miR-451 knockout mice compared with control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in cardiomyocyte-specific miR-451 knockout mouse hearts compared with control mouse hearts. Our results demonstrate that miR-451 is involved in diabetic cardiomyopathy through suppression of the LKB1/AMPK pathway. © 2014 American Heart Association, Inc.

  17. Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet.

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    Viana Gonçalves, Igor Cândido; Cerdeira, Cláudio Daniel; Poletti Camara, Eduardo; Dias Garcia, José Antônio; Ribeiro Pereira Lima Brigagão, Maísa; Bessa Veloso Silva, Roberta; Bitencourt Dos Santos, Gérsika

    2017-09-01

    Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed. A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group. In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Delayed hemothorax superimposed on extrapleural hematoma after blunt chest injury: a case report.

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    Masuda, Ryota; Ikoma, Yoichiro; Oiwa, Kana; Nakazato, Kenei; Takeichi, Haruka; Iwazaki, Masayuki

    2013-09-20

    We report a case showing delayed hemothorax superimposed on extrapleural hematoma after blunt chest injury. The patient was a 56-year-old man with a medical history of alcoholic hepatopathy who presented with a chief complaint of dyspnea on exertion. One month prior to presentation, he had sustained a fall that had resulted in left simple rib fracture. A chest radiograph taken at the time of injury showed notable reduction in the permeability of the left lung field along with high pulmonary collapse as well as rightward deviation of the shadow of the inferior mediastinum. Chest CT images showed a region of low absorption in the thoracic cavity with septi. Thoracic drainage was performed (1,300 mL total) and hemothorax was diagnosed. Thoracoscopic examination was then performed. When the inside of the thorax was observed, what had been presumed to be the septi of a multilocular fluid collection was found to be actually the parietal pleura, and a hematoma was confirmed inside the extrapleural cavity. The hematoma inside the extrapleural cavity was managed with lavage and drainage, and drainage tubes were placed inside both the thoracic cavity and extrapleural cavity at the end of the procedure. The patient's postoperative course was uneventful, and he was discharged on postoperative day 4.

  19. Butein induction of HO-1 by p38 MAPK/Nrf2 pathway in adipocytes attenuates high-fat diet induced adipose hypertrophy in mice.

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    Wang, Zheng; Ka, Sun-O; Lee, Youngyi; Park, Byung-Hyun; Bae, Eun Ju

    2017-03-15

    Adipose tissue inflammation and oxidative stress are key components in the development of obesity and insulin resistance. Heme oxygenase (HO)-1 in adipocytes protects against obesity and adipose dysfunction. In this study, we report the identification of butein, a flavonoid chalcone, as a novel inducer of HO-1 expression in adipocytes in vitro and in vivo. Butein upregulated HO-1 mRNA and protein expression in 3T3-L1 adipocytes, accompanied by Kelch-Like ECH-Associated Protein (Keap) 1 degradation and increase in the nuclear level of nuclear factor erythroid 2-related factor 2 (Nrf2). Butein modulation of Keap1 and Nrf2 as well as HO-1 upregulation was reversed by pretreatment with p38 MAPK inhibitor SB203580, indicating the involvement of p38 MAPK in butein activation of Nrf2 in adipocytes. In addition, HO-1 activation by butein led to the inhibitions of reactive oxygen species and adipocyte differentiation, as evidenced by the fact that butein repression of reactive oxygen species and adipogenesis was reversed by pretreatment with HO-1 inhibitor SnPP. Induction of HO-1 expression by butein was also demonstrated in the adipose tissue of C57BL/6 mice fed a high-fat diet administered along with butein for three weeks, and correlated with the inhibitions of adiposity and adipose tissue inflammation, which were reversed by co-administration of SnPP. Altogether, our results demonstrate that butein activates the p38 MAPK/Nrf2/HO-1 pathway to act as a potent inhibitor of adipose hypertrophy and inflammation in a diet-induced obesity model and thus has potential for suppressing obesity-linked metabolic syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fatness

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    Hansen, Anne Katrine Kleberg

    In 1727, the English physician Thomas Short wrote: “I believe no Age did ever afford more instances of Corpulency than our own.” Even in the 18th century, fatness was addressed as an issue of special contemporary concern. This thesis probes concepts and perceptions of fatness in Western European...... Medicine c. 1700–1900. It has been written with particular attention to whether and how fatness has been regarded as a disease during that period in history. One purpose of the thesis is to investigate the immediate period before fatness allegedly became problematized. Another purpose has been to grasp...

  1. Extrapleural paravertebral CT guided fine needle biopsy of subcarinal lymph nodes

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    Tantawy, Wahid H., E-mail: tantawyw@yahoo.com [Radiology Department, Faculty of Medicine, Ain Shams University, Egypt Abbassyia square, Cairo (Egypt); El-Gemeie, Emad H. [Pathology Department, National Cancer Institute, Fom El Khalige Faculty of Medicine, Cairo University (Egypt); Ibrahim, Ahmed S., E-mail: asibrahima@gmail.com [Radiology Department, Faculty of Medicine, Ain Shams University, Egypt Abbassyia square, Cairo (Egypt); Mohamed, Mona A. [Radiology Department, Faculty of Medicine, Ain Shams University, Egypt Abbassyia square, Cairo (Egypt)

    2012-10-15

    Purpose: To report our experience in CT guided extrapleural paravertebral subcarinal lymph biopsy using a thin 25 gauge (25 G) thin needle without the need of injection of saline to widen the mediastinum. Materials and methods: Biopsy was performed using a 25 G needle which was advanced lateral to the vertebral body between the endothoracic fascia and the parietal pleura to gain access to subcarinal lymph nodes. One hundred and forty one patients were included in the study (74 females, 57 males). No artificial widening of the mediastinum using saline injection was required. The study was performed in the presence of a cytopathologist; sensitivity and specificity rates were calculated. Complications were documented for each case especially for pneumothorax and haemorrhage. Results: Cytopathological diagnosis was reached in all cases. All re-aspirations were done in the same session to reach a primary diagnosis at the time of the biopsy. Imunophenotyping study was done in 94 cases to confirm the primary diagnosis and to classify the malignant lesions. No pneumothorax was encountered. Small haematomas were noted in 5 cases (3.5%). Cytopathology showed a sensitivity of 97.2% and specificity of 100%. By adding immunophenotyping a 100% sensitivity and specificity was achieved. Conclusion: Fine needle aspiration cytology (FNAC) using a 25 gauge needle for subcarinal lymph nodes via a percutaneous extrapleural paravertebral CT guided approach is a safe, minimally invasive, and tolerable procedure yielding a high sensitivity and specificity rates without the need of artificial widening.

  2. Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege–Potter syndrome

    Directory of Open Access Journals (Sweden)

    Andrew J. Degnan, MD, MPhil

    2017-03-01

    Full Text Available We report a rare case of metastatic malignant solitary fibrous tumor (SFT that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

  3. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Du, Kevin L; Both, Stefan; Friedberg, Joseph S; Rengan, Ramesh; Hahn, Stephen M; Cengel, Keith A

    2010-09-01

    Intensity modulated radiation therapy (IMRT) has recently been proposed for the treatment of malignant pleural mesothelioma (MPM). Here, we describe our experience with a multimodality approach for the treatment of mesothelioma, incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an intraoperative adjuvant to surgical debulking. The median radiation dose to the planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our series, 1 patient experienced respiratory failure secondary to radiation pneumonitis that did not require mechanical ventilation. Multimodality therapy combining surgery with increased doses of radiation using IMRT, and newer treatment modalities such as PDT , appears safe. Future prospective analysis will be needed to demonstrate efficacy of this approach in the treatment of malignant mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are needed and provide the promise of improved local control and quality of life in a carefully chosen multidisciplinary approach.

  4. Should we continue to offer extrapleural pneumonectomy to selected mesothelioma patients? A single center experience comparing surgical and non-surgical management.

    Science.gov (United States)

    Baud, Mariette; Bobbio, Antonio; Lococo, Filippo; Regnard, Jean-François; Alifano, Marco

    2014-11-01

    Malignant pleural mesothelioma remains an incurable disease for which the optimal therapeutic approach remains an extremely debated issue. Though not yet clearly defined, a subset of patients may benefit from a surgery-based multimodal treatment plan, beyond what would be expected with non-surgical therapies only. Indeed, despite some disappointing results on the feasibility of a multimodality treatment (chemotherapy ± surgery and post-operative radiation therapy) based on a lung sacrificing surgery (extrapleural pleuropnemonectomy) have been recently reported, the question concerning the role of extrapleural pneumonectomy in selected mesothelioma patients is still unanswered. In the light of this, we have reviewed our mono-institutional retrospective experience in the mesothelioma management, discussing on the role of extrapleural pneumonectomy in the multimodality treatment. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Simultaneously anterior decompression and posterior instrumentation by extrapleural retroperitoneal approach in thoracolumbar lesions

    Directory of Open Access Journals (Sweden)

    Jain Anil

    2010-01-01

    Full Text Available Background: Anterior decompression with posterior instrumentation when indicated in thoracolumbar spinal lesions if performed simultaneously in single-stage expedites rehabilitation and recovery. Transthoracic, transdiaphragmatic approach to access the thoracolumbar junction is associated with significant morbidity, as it violates thoracic cavity; requires cutting of diaphragm and a separate approach, for posterior instrumentation. We evaluated the clinical outcome morbidity and feasibility of extrapleural retroperitoneal approach to perform anterior decompression and posterior instrumentation simultaneously by single "T" incision outcome in thoracolumbar spinal trauma and tuberculosis. Patients and Methods: Forty-eight cases of tubercular spine (n = 25 and fracture of the spine (n = 23 were included in the study of which 29 were male and 19 female. The mean age of patients was 29.1 years. All patients underwent single-stage anterior decompression, fusion, and posterior instrumentation (except two old traumatic cases via extrapleural retroperitoneal approach by single "T" incision. Tuberculosis cases were operated in lateral position as they were stabilized with Hartshill instrumentation. For traumatic spine initially posterior pedicle screw fixation was performed in prone position and then turned to right lateral position for anterior decompression by same incision and approach. They were evaluated for blood loss, duration of surgery, superficial and deep infection of incision site, flap necrosis, correction of the kyphotic deformity, and restoration of anterior and posterior vertebral body height. Results: In traumatic spine group the mean duration of surgery was 269 minutes (range 215-315 minutes including the change over time from prone to lateral position. The mean intraoperative blood loss was 918 ml (range 550-1100 ml. The preoperative mean ASIA motor, pin prick and light touch score improved from 63.3 to 74.4, 86 to 94.4 and 86 to 96 at

  6. Simultaneously anterior decompression and posterior instrumentation by extrapleural retroperitoneal approach in thoracolumbar lesions.

    Science.gov (United States)

    Jain, Anil K; Dhammi, Ish Kumar; Jain, Saurabh; Kumar, Jaswant

    2010-10-01

    Anterior decompression with posterior instrumentation when indicated in thoracolumbar spinal lesions if performed simultaneously in single-stage expedites rehabilitation and recovery. Transthoracic, transdiaphragmatic approach to access the thoracolumbar junction is associated with significant morbidity, as it violates thoracic cavity; requires cutting of diaphragm and a separate approach, for posterior instrumentation. We evaluated the clinical outcome morbidity and feasibility of extrapleural retroperitoneal approach to perform anterior decompression and posterior instrumentation simultaneously by single "T" incision outcome in thoracolumbar spinal trauma and tuberculosis. Forty-eight cases of tubercular spine (n = 25) and fracture of the spine (n = 23) were included in the study of which 29 were male and 19 female. The mean age of patients was 29.1 years. All patients underwent single-stage anterior decompression, fusion, and posterior instrumentation (except two old traumatic cases) via extrapleural retroperitoneal approach by single "T" incision. Tuberculosis cases were operated in lateral position as they were stabilized with Hartshill instrumentation. For traumatic spine initially posterior pedicle screw fixation was performed in prone position and then turned to right lateral position for anterior decompression by same incision and approach. They were evaluated for blood loss, duration of surgery, superficial and deep infection of incision site, flap necrosis, correction of the kyphotic deformity, and restoration of anterior and posterior vertebral body height. In traumatic spine group the mean duration of surgery was 269 minutes (range 215-315 minutes) including the change over time from prone to lateral position. The mean intraoperative blood loss was 918 ml (range 550-1100 ml). The preoperative mean ASIA motor, pin prick and light touch score improved from 63.3 to 74.4, 86 to 94.4 and 86 to 96 at 6 month of follow-up respectively. The mean preoperative

  7. Adoption of pleurectomy and decortication for malignant mesothelioma leads to similar survival as extrapleural pneumonectomy.

    Science.gov (United States)

    Batirel, Hasan Fevzi; Metintas, Muzaffer; Caglar, Hale Basak; Ak, Guntulu; Yumuk, Perran Fulden; Yildizeli, Bedrettin; Yuksel, Mustafa

    2016-02-01

    We changed our surgical approach to malignant pleural mesothelioma (MPM) in August 2011 and adopted pleurectomy and decortication (PD) instead of extrapleural pneumonectomy (EPP). In this study, we analyzed our perioperative and survival results during the 2 periods. All patients who underwent surgical intervention for MPM during 2003-2014 were included. Data were retrospectively analyzed from a prospective database. Before August 2011, patients underwent evaluation for EPP and adjuvant chemoradiation (group 1). After August 2011, patients were evaluated for PD and adjuvant chemotherapy and/or radiation (group 2). Demographic characteristics, surgical technique, histology, side, completeness of resection, and types of treatments were recorded. Statistics was performed using Student t test, χ(2) tests, uni- and multivariate regression, and Kaplan-Meier survival analysis. The same surgical team operated on 130 patients. Median age was 55.7 years (range, 26-80 years) and 76 were men. EPP and extended PD was performed in 72 patients. Ninety-day mortality was 10%. Median survival was 17.8 months with a 5-year survival rate of 14%. Uni- and multivariate analyses showed that epithelioid histology, stage N0, and trimodality treatment were associated with better survival (P = .039, P = .012, and P < .001, respectively). Demographic variables and overall survival (15.6 vs 19.6 months, respectively) were similar between the groups, whereas nonepithelioid histology, use of preoperative chemotherapy, and incomplete resections were more frequent in group 2 (P < .001, P < .001, and P = .006, respectively). Follow-up was shorter in group 2 (22.5 ± 20.6 vs 16.4 ± 10.9 months; P < .001). Adoption of PD as the main surgical approach is not associated with survival disadvantage in the surgical treatment of MPM. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  8. Propensity matched comparison of extrapleural pneumonectomy and pleurectomy/decortication for mesothelioma patients†.

    Science.gov (United States)

    Kostron, Arthur; Friess, Martina; Inci, Ilhan; Hillinger, Sven; Schneiter, Didier; Gelpke, Hans; Stahel, Rolf; Seifert, Burkhardt; Weder, Walter; Opitz, Isabelle

    2017-05-01

    The objective of this retrospective study was to assess perioperative outcomes, overall survival and freedom from recurrence after induction chemotherapy followed by extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) in patients with mesothelioma in a propensity score matched analysis. Between September 1999 and August 2015, 167 patients received multimodality treatment (platinum-based chemotherapy followed by EPP [ n =  141] or P/D [ n =  26]). We performed 2:1 propensity score matching for gender, laterality, epithelioid histological subtype and International Mesothelioma Interest Group (iMig) stage (52 EPP and 26 P/D). Postoperative major morbidity (48% vs 58%, P =  0.5) was similar in both groups; however, the complication profile and severity were different and favoured P/D; the 90-day mortality (8% vs 0%, P =  0.3) rate was lower in P/D although not statistically significant. Prolonged air leak (≥10 days) occurred in 15 patients (58%) undergoing P/D. The intensive care unit stay was significantly longer after EPP ( P =  0.001). Freedom from recurrence was similar for both groups (EPP: median 15 months, 95% confidence interval [CI]: 10-21; P/D: 13 months, 95% CI: 11-17) ( P =  0.2). Overall survival was significantly longer for patients undergoing P/D (median 32 months, 95% CI: 29-35) compared to EPP (23 months, 95% CI: 21-25) ( P =  0.031), but in the P/D group many cases were censored (73%) and the follow-up time was relatively short. P/D and EPP seem to have similar rates of major morbidity, although the profile of complications is different and more severe after EPP. Freedom from recurrence is comparable in both groups whereas improved overall survival needs to be confirmed in a large patient group with longer follow-up.

  9. Clinical experience of volumetric modulated arc therapy for malignant pleural mesothelioma after extrapleural pneumonectomy.

    Science.gov (United States)

    Kimura, Tomoki; Doi, Yoshiko; Nakashima, Takeo; Imano, Nobuki; Katsuta, Tsuyoshi; Takahashi, Shigeo; Kenjo, Masahiro; Ozawa, Shuichi; Murakami, Yuji; Nagata, Yasushi

    2015-03-01

    The purpose of this study was to evaluate the efficacy and safety of volumetric modulated arc therapy (VMAT) after extrapleural pneumonectomy (EPP) in patients with malignant pleural mesothelioma (MPM). A total of 15 patients who received VMAT after EPP were enrolled. All patients were males, and the median age was 67 years (Stage IB in two, II in six, and III in seven patients). The clinical target volume (CTV) included the entire preoperative ipsilateral hemithorax and involved nodal stations. The CTV was generally expanded by 10-15 mm beyond the planning target volume (PTV). The dose prescription was designed to cover 95% of the PTV with 54 Gy in 30 fractions. The median follow-up period was 11 months. Treatment-related toxicities were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) ver. 4. One-year local control, disease-free survival, and overall survival rates were 55.7% [95% confidence interval (CI): 25.6-85.8%], 29.3% (95% CI: 5.3-53.3%), and 43.1% (95% CI: 17.1-69.0%), respectively. According to the histological analysis, the one-year LC rate was significantly worse in patients with non-epithelial type (biphasic and sarcomatoid types) than in patients with epithelial type [epithelial type: 83.3% (95% CI, 53.5-100%), non-epithelial type: 0% (95% CI, 0%), P = 0.0011]. Grade 3 pneumonitis after VMAT was observed in three patients (20.0%); however, no patients died of pulmonary toxicity. VMAT appears to be relatively safe for patients with MPM after EPP because of the low pulmonary dose. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  10. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  11. Premenarchal labia minora hypertrophy

    Directory of Open Access Journals (Sweden)

    Karoon Agrawal

    2016-01-01

    Full Text Available Labia minora hypertrophy is a relatively uncommon surgical entity being popularised in the realm of vulvovaginal plastic surgeries. Apart from the unaesthetic appearance of the hypertrophied minora, these cases are also associated with itching, hygiene problem, pain while sitting down, sports activities, difficulty in wearing tight clothing, bleeding and discomfort while or after sexual intercourse, social embarrassment, insecurity and psychological diminution of confidence and self-esteem. In a country like India, due to sociocultural reasons, patients hesitate to consult a doctor for such deformities. Most of the patients suffer in silence for years. Although common in the west, very few surgeons in the country perform this simple and rewarding surgery. Here, we are presenting a case of premenarchal juvenile labia minora hypertrophy (JLMH in an 8-year-old child. Labial hypertrophy in this age group is uncommon. We were unable to find hypertrophy of labia minora in the eight-year-old child on English literature search.

  12. The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication.

    Science.gov (United States)

    Sharkey, Annabel J; Tenconi, Sara; Nakas, Apostolos; Waller, David A

    2016-06-01

    For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected population, have prompted a transition in our practice towards extended pleurectomy/decortication (EPD). The aim of this study was to determine the effects an intentional transition from EPP to EPD has had on patient outcome. Data from 362 patients undergoing radical surgery (229 EPD, 133 EPP) during 1999-2014 were included. Demographics and outcome were compared between the two groups; EPP versus EPD. The median age of patients undergoing EPD was significantly higher than those undergoing EPP [57 years (range 14-70 years) vs 65 years (range 42-81 years), P < 0.001]. There was a significantly higher proportion of patients with performance status ≥1 in the EPD group (46.3 vs 35.4%, P = 0.047). There was no difference in the median length of hospital stay between the two groups [14 days (range 1-133 days) vs 13 days (range 0-93 days), P = 0.409]. There was also no difference between the groups in terms of in-hospital mortality (EPP 5.3% and EPD 6.6%, P = 0.389), 30-day mortality [EPP 8 (6.0%) and EPD 8 (3.5%), P = 0.294] or 90-day mortality [EPP 18 (13.5%) and EPD 21 (9.2%), P = 0.220]. There was a significantly higher early reoperation rate in the EPP group (15.0 vs 6.2%, P = 0.008) but a significantly higher late reoperation rate in the EPD group (0.8 vs 5.3%, P = 0.037). There was no significant difference in overall survival or disease-free interval between the two groups (P = 0.899 and P = 0.399, respectively). However, overall survival was significantly greater in patients over the age of 65 undergoing EPD (12.5 vs 4.7 months, P = 0.001). The transition from EPP to EPD in our standard practice has enabled us to operate on more elderly, frail patients with no significant increase in use of hospital resources, and without

  13. Skeletal Muscle Hypertrophy and Cardiometabolic Benefits after Spinal Cord Injury

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0671 TITLE: Skeletal Muscle Hypertrophy and Cardiometabolic Benefits after Spinal Cord Injury PRINCIPAL...29 Sep 2016 4. TITLE AND SUBTITLE Spinal Cord Injury 5a. CONTRACT NUMBER Skeletal Muscle Hypertrophy and Cardiometabolic Benefits after Spinal...metabolism, increasing leg muscle size and preventing an increase in leg fat mass. 15. SUBJECT TERMS RESISTANCE TRAINING, SPINAL CORD INJURY , BODY

  14. Left Ventricular Hypertrophy

    Science.gov (United States)

    ... need to restrict certain physical activities, such as weightlifting, which may temporarily raise your blood pressure. The ... Accessed April 6, 2015. Chatterjee S, et al. Meta-analysis of left ventricular hypertrophy and sustained arrhythmias. American ...

  15. [Rationale and complications of the anterior-lateral extrapleural retroperitoneal approach for unstable thoracolumbar fractures: Experience in 86 consecutive patients].

    Science.gov (United States)

    Delgado-López, Pedro David; Rodríguez-Salazar, Antonio; Martín-Velasco, Vicente; Martín-Alonso, Javier; Castilla-Díez, José Manuel; Galacho-Harriero, Ana; Araús-Galdós, Elena

    To describe the rationale, pros and cons, and complications of the anterior-lateral extrapleural retroperitoneal approach for unstable (TLICS>4) thoracolumbar fractures. Clinical and radiological data and outcomes from a cohort treated surgically via said approach were retrospectively reviewed. All patients were operated on exclusively by 5 neurosurgeons trained in spine surgery. Between June 1999 and December 2015, 86 patients underwent surgery (median age 42years, most common level: L1). Approximately 32.5% presented with a preoperative neurological defect. After surgery (mean duration: 275minutes), 75.6% presented with no neurological sequelae and only one-third required blood transfusion. Median postoperative stay was 7days. Correction of kyphosis was considered adequate and suboptimal but acceptable in 91% and 9% of the patients, respectively. Complications occurred in 36 patients, the majority being transient. We observed failure of the construct in 2 cases (collapse of an expandable cage and extrusion of a locking screw). No infections, vascular or visceral lesions, permanent neurological worsening or mortality occurred during hospitalisation. One patient ultimately needed additional posterior fixation due to persistence of pain. Median follow-up was 252days (27.9% was lost to follow-up). The extrapleural extraperitoneal approach provides solid anterior reconstruction, allows wide decompression of the spinal canal, and permits adequate and long-lasting correction of kyphosis. The rates of infection, construct failure, need for reoperation and vascular or visceral lesions are minimal. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Body-building without power training : Endogenously regulated pectoral muscle hypertrophy in confined shorebirds

    NARCIS (Netherlands)

    Dietz, MW; Piersma, T; Dekinga, A

    1999-01-01

    Shorebirds such as red knots Calidris canutus routinely make migratory flights of 3000 km or more. Previous studies on this species, based on compositional analyses, suggest extensive pectoral muscle hypertrophy in addition to fat storage before take-off. Such hypertrophy could be due to power

  17. Ventricular hypertrophy in cardiomyopathy.

    Science.gov (United States)

    Oakley, C

    1971-01-01

    Semantic difficulties arise when hypertrophic obstructive cardiomyopathy is seen without obstruction and with congestive failure, and also when congestive cardiomyopathy is seen with gross hypertrophy but without heart failure. Retention of a small left ventricular cavity and a normal ejection fraction characterizes hypertrophic cardiomyopathy at all stages of the disorder. Congestive cardiomyopathy is recognized by the presence of a dilated left ventricular cavity and reduced ejection fraction regardless of the amount of hypertrophy and the presence or not of heart failure. Longevity in congestive cardiomyopathy seems to be promoted when hypertrophy is great relative to the amount of pump failure as measured by increase in cavity size. Conversely, death in hypertrophic cardiomyopathy is most likely when hypertrophy is greatest at a time when outflow tract obstruction has been replaced by inflow restriction caused by diminishing ventricular distensibility. Hypertrophy is thus beneficial and compensatory in congestive cardiomyopathy, whereas it may be the primary disorder and eventual cause of death in hypertrophic cardiomyopathy. Reasons are given for believing that hypertension may have been the original cause of left ventricular dilatation in some case of congestive cardiomyopathy in which loss of stroke output thenceforward is followed by normotension. Development of severe hypertension in these patients after recovery from a prolonged period of left ventricular failure with normotension lends weight to this hypothesis. No fault has been found in the large or small coronary arteries in either hypertrophic cardiomyopathy or congestive cardiomyopathy when they have been examined in life by selective coronary angiography, or by histological methods in biopsy or post-mortem material. Coronary blood supply may be a limiting factor in the compensatory hypertrophy of congestive cardiomyopathy, and the ability to hypertrophy may explain the better prognosis of some

  18. Left Ventricular Hypertrophy

    Science.gov (United States)

    ... AskMayoExpert. What tests are needed to confirm the diagnosis of hypertrophic cardiomyopathy (HCM) and what is the role of genetic testing? Rochester, Minn.: Mayo Foundation for Medical Education and Research; ... diagnosis in patients with hypertrophied left ventricles. Heart. 2014; ...

  19. Tumour-to-tumour metastasis: male breast carcinoma metastasis arising in an extrapleural solitary fibrous tumour - a case report.

    Science.gov (United States)

    Scheipl, Susanne; Moinfar, Farid; Leithner, Andreas; Sadoghi, Patrick; Jorgensen, Mette; Rinner, Beate; Liegl, Bernadette

    2014-11-25

    Tumour-to-tumour metastasis (TTM) occurs when one tumour metastasises to a separate tumour within the same individual. TTM is observed frequently in breast cancer but has not been described in male breast cancer. In addition reports describing solitary fibrous tumours (SFT) of the pleura hosting other neoplasms' metastases are limited. We report an exceptional case of male breast cancer metastasising to an extrapleural SFT, occurring in the subcutaneous tissue of the back of a 68-year old Caucasian patient. A 68-year old male was diagnosed with a metastasising ductal breast cancer. He was treated by mastectomy of the right breast and axillary lymph-adenectomy. Further staging revealed an increasing subcutaneous expansion located on the patient's back. Excision biopsy confirmed a SFT hosting a breast cancer metastasis. The patient received palliative chemotherapy but died of disease seven years after initial diagnosis. The abundance of blood vessels within these lesions might predispose SFTs for an involvement in TTM. This case describes the possibility of concurrent rare occurrences and reminds clinicians, as well as pathologists, to be open-minded and fastidious about their differential diagnoses, sampling and examination of histological specimens. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_203.

  20. [Efficiency of a new method for extrapleural plastic repair of the apex of the lung in disseminated destructive tuberculosis].

    Science.gov (United States)

    Kravchenko, A F; Ivanov, Iu S; Shamaev, V E

    2003-01-01

    The Thoracic Department, Yarutsk Research Institute of Tuberculosis, has developed a new method for extrapleural plastic repair of the apex of the lung in destructive tuberculosis. The essence of the method is that pneumolysis of the apex of the lung and its bringing down is made by the well-known procedure described by L. K. Bogush after thoracoplasty. To prevent its expanding, the apex of the lung is fixed by a hammock mesh prepared before surgery. For this, No. 2 polysorb thresh is used and a 10 x 14-cm mesh is woven. The cells measure 2 x 2 cm. Then the mesh is placed in disinfectant solution. Surgery was performed in 41 patients with generalized fibrocavernous, disseminated, cavernous, and infiltrative pulmonary tuberculosis, by yielding 90.3% efficiency. The developed operation may be used during a non-stabilized tuberculous process, anterior and upper lung destructions and in the presence of a giant cavity in the lung tissue. The time course of changes in the indices of external respiratory function is indicative of a more rapid and qualitative recovery of the external respiratory apparatus and of a rapid adaptation of compensatory respiratory mechanisms in the postoperative period.

  1. Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution.

    Science.gov (United States)

    Bece, Andrej; Tin, Mo Mo; Martin, Darren; Lin, Robert; McLean, Jocelyn; McCaughan, Brian

    2015-06-01

    We aim to report the outcome of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiotherapy with or without chemotherapy at a single Australian institution. Between July 2004 and March 2013, 53 patients were referred for radiation treatment following EPP, of whom 49 were suitable for adjuvant treatment. Radiation treatment initially involved a 3D conformal, mixed electron/photon technique, delivering 45-50.4 Gy in 25-28 fractions (31 patients) and subsequently a nine-field intensity-modulated radiotherapy technique, delivering 50.4-54 Gy in 28-30 fractions (18 patients). Fifty-five per cent of patients also received pre-operative chemotherapy. We assessed toxicity, disease-specific and overall survival in patients who commenced radiation treatment. Forty-one patients (84%) completed treatment as prescribed. Six patients stopped prematurely due to toxicity, and two with disease progression. Most patients discontinuing due to toxicity received over 90% of the prescribed dose. Common acute toxicities included nausea, fatigue, anorexia and dermatitis. Severe early toxicities were rare. Late toxicities were uncommon, with the exception of a persistent elevation in liver enzymes in those with right-sided disease. Neither clinical hepatitis nor radiation pneumonitis was documented. With a median follow up of 18.7 months, median disease-free and overall survival were 21.6 and 30.5 months, respectively, and 2-year overall survival was 57.3%. Hemithoracic radiotherapy following EPP, although associated with significant early toxicity, is well tolerated. Most patients complete the prescribed treatment, and clinically significant late toxicities are rare. © 2015 The Royal Australian and New Zealand College of Radiologists.

  2. The evolution of the diminishing role of extrapleural pneumonectomy in the surgical management of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Azzouqa AG

    2016-11-01

    Full Text Available Abdel-Ghani Azzouqa,1 James P Stevenson2 1Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, 2Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA Abstract: Malignant pleural mesothelioma is an uncommon and aggressive thoracic malignancy that is rarely curable, even when multimodality therapy is used. Systemic chemotherapy is the primary treatment for the majority of patients with this disease; however, surgical resection may benefit a subset of patients with early-stage disease. The surgical approach that offers the best outcomes remains an area of controversy, with data from retrospective comparisons being the only guide. Historically, extrapleural pneumonectomy (EPP has been the standard procedure, carrying with it a cost of significant morbidity and impact on quality of life that has raised questions regarding its routine application. Over the past two decades as surgical techniques have been refined and survival data with EPP in large case series have been reported, the paradigm has evolved toward the use of lung-sparing pleural resections such as pleurectomy/decortication (P/D and extended P/D. The identification of patients who may benefit from EPP over pleurectomy has proven problematic, and the larger question regarding the impact of any type of surgical intervention on outcomes for pleural mesothelioma patients is still an area of investigation. Uniform treatment approaches have been difficult to develop due to the relatively small numbers of patients with this disease, the use of a staging system that does not readily identify those who may benefit from more aggressive therapy, and the institutional biases that have resulted from the growth of multimodality centers of excellence. Keywords: mesothelioma, pneumonectomy, thoracic surgical procedure, multimodal treatment 

  3. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Corrección del pectus excavatum por vía extrapleural sin toracoscopio, en un paciente con cirugías torácicas previas

    Directory of Open Access Journals (Sweden)

    Mario López

    2013-07-01

    Full Text Available Se presenta un caso de un niño de 6 años de edad, con diagnóstico de pectus excavatum a quien le habían realizado tres intervenciones quirúrgicas en el hemitórax izquierdo, se realizó la corrección del pectus excavatum, empleando la técnica de Nuss modificada por vía extrapleural sin el empleo de toracoscopio. El paciente no presentó complicaciones en el intraoperatorio ni en el post operatorio. A los seis meses de seguimiento, la evolución clínica, anatómica y funcional fue favorable.

  5. Modulation of impact of obesity in pathological and physiological cardiac hypertrophy by orlistat

    OpenAIRE

    Singh, Manjeet; Singh, Randhir; Krishan, Pawan

    2010-01-01

    High fat diet (30 % fat) was used to induce obesity in rats. Male wistar rats were kept at high fat diet for 90 days and subjected to partial abdominal aortic constriction (PAAC) at 62nd day and continued upto 90th day. Similarly rats were kept at high fat diet for 90 days and subjected to chronic swimming training (CST) at 46th day and continued upto 90th day. Obesity was assessed by measuring body weight, WHR ratio, obesity index and adiposity index. Cardiac hypertrophy was asse...

  6. Kshara application for turbinate hypertrophy

    Directory of Open Access Journals (Sweden)

    Vijay Kumar S Kotrannavar

    2013-01-01

    Full Text Available Nasapratinaha (nasal obstruction is a commonly encountered disease in clinical practice. It is one of the nasal disorders, explained in Ayurveda, having nasal obstruction leading to difficulty in breathing as the main cardinal feature. In contemporary science, this condition can be correlated with various diseases such as turbinate hypertrophy, deviated nasal septum, nasal mass, mucosal congestion, allergic rhinitis, and others; among which turbinate hypertrophy is a common cause. Turbinate hypertrophy can be treated with surgical and medical methods. The medical treatment has limitation for prolonged use because of health purpose, surgical approaches too have failed to achieve desired results in turbinate hypertrophy due to complications and high recurrence rate. The medical and surgical managements have their own limitations, merits, and demerits like synechiae formation, rhinitis sicca, severe bleeding, or osteonecrosis of the turbinate bone A parasurgical treatment explained in Ayurveda, known as kshara pratisarana, which is a minimal invasive and precise procedure for this ailment, tried to overcome this problem. ′Kshara Karma′ is a popular treatment modality in Ayurveda, which has been advocated in disorders of nose like arbuda (tumor and adhimamsa (muscular growth. Clinical observation has shown its effectiveness in the management of turbinate hypertrophy. A case report of 45-year-old male who presented with complaints of frequent nasal obstruction, nasal discharge, discomfort in nose, and headache; and diagnosed as turbinate hypertrophy has been presented here. The patient was treated with one application of Kshara over the turbinates. The treatment was effective and no recurrence was noticed in the follow up.

  7. Facts about polyunsaturated fats

    Science.gov (United States)

    ... polyunsaturated fat; Heart disease - polyunsaturated fat; Peripheral artery disease - polyunsaturated fat; PAD - polyunsaturated fat; Stroke - polyunsaturated fat; CAD - polyunsaturated fat; Heart healthy diet - polyunsaturated fat

  8. Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs.

    Science.gov (United States)

    Xia, Jihan; Zhang, Yuanyuan; Xin, Leilei; Kong, Siyuan; Chen, Yaoxing; Yang, Shulin; Li, Kui

    2015-01-01

    A long-term high-energy diet affects human health and leads to obesity and metabolic syndrome in addition to cardiac steatosis and hypertrophy. Ectopic fat accumulation in the heart has been demonstrated to be a risk factor for heart disorders, but the molecular mechanism of heart disease remains largely unknown. Bama miniature pigs were fed a high-fat, high-sucrose diet (HFHSD) for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased body weight (2.73-fold, Pcardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. Microarray analyses revealed that 1,022 genes were significantly differentially expressed (Pcardiac steatosis, and hypertrophy and provides insights into the molecular mechanisms of hypertrophy and fatty heart to facilitate further research.

  9. Histologically Measured Cardiomyocyte Hypertrophy Correlates with Body Height as Strongly as with Body Mass Index

    Directory of Open Access Journals (Sweden)

    Richard E. Tracy

    2011-01-01

    Full Text Available Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH. This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height2.7 as a proxy for lean body mass and body mass index (BMI as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

  10. Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report

    Directory of Open Access Journals (Sweden)

    Schutt Robert C

    2013-01-01

    Full Text Available Abstract Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

  11. Mitochondria in cardiac hypertrophy and heart failure

    Science.gov (United States)

    Rosca, Mariana G.; Tandler, Bernard; Hoppel, Charles L.

    2013-01-01

    Heart failure (HF) frequently is the unfavorable outcome of pathological heart hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in response to exercise and leads to full adaptation of contractility to the increased wall stress, pathological hypertrophy occurs in response to volume or pressure overload, ultimately leading to contractile dysfunction and HF. Because cardiac hypertrophy impairs the relationship between ATP demand and production, mitochondrial bioenergetics must keep up with the cardiac hypertrophic phenotype. We review data regarding the mitochondrial proteomic and energetic remodeling in cardiac hypertrophy, as well as the temporal and causal relationship between mitochondrial failure to match the increased energy demand and progression to cardiac decompensation. We suggest that the maladaptive effect of sustained neuroendocrine signals on mitochondria leads to bioenergetic fading which contributes to the progression from cardiac hypertrophy to failure. PMID:22982369

  12. ULTRASONIC EXAMINATION OF THE BENIGN PROSTATIC HYPERTROPHY

    OpenAIRE

    棚橋, 善克

    1982-01-01

    In normal cases, prostatic section shows triangular shape and inner gland occupies a small part in only upper sections as a echogenic portion. In prostatic hypertrophy cases, inner gland occupies more part of the prostate and outer gland is shown as a half moon shape, in late stage of hypertrophy, inner gland occupies almost whole the part of the prostate, and compressed outer gland is visualized as an orange peel in postero-inferior portion. In some cases with prostatic hypertrophy, some nod...

  13. [Asymmetric hypertrophy of the masticatory muscles].

    Science.gov (United States)

    Arzul, L; Corre, P; Khonsari, R H; Mercier, J-M; Piot, B

    2012-06-01

    Hypertrophy of the masticatory muscles most commonly affects the masseter. Less common cases of isolated or associated temporalis hypertrophy are also reported. Parafunctional habits, and more precisely bruxism, can favor the onset of the hypertrophy. This condition is generally idiopathic and can require both medical and/or surgical management. A 29-year-old patient was referred to our department for an asymmetric swelling of the masticatory muscles. Physical examination revealed a bilateral hypertrophy of the masticatory muscles, predominantly affecting the right temporalis and the left masseter. Major bruxism was assessed by premature dental wearing. The additional examinations confirmed the isolated muscle hypertrophy. Benign asymmetric hypertrophy of the masticatory muscles promoted by bruxism was diagnosed. Treatment with injections of type A botulinum toxin was conducted in association with a splint and relaxation. Its effectiveness has been observed at six months. Few cases of unilateral or bilateral temporalis hypertrophy have been reported, added to the more common isolated masseter muscles hypertrophy. The diagnosis requires to rule out secondary hypertrophies and tumors using Magnetic Resonance Imaging. The condition is thought to be favoured by parafunctional habits such as bruxism. The conservative treatment consists in reducing the volume of the masticatory muscles using intramuscular injections of type A botulinum toxin. Other potential conservative treatments are wearing splints and muscle relaxant drugs. Surgical procedures aiming to reduce the muscle volume and/or the bone volume (mandibular gonioplasty) can be proposed. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Genetics Home Reference: myostatin-related muscle hypertrophy

    Science.gov (United States)

    ... Conditions myostatin-related muscle hypertrophy myostatin-related muscle hypertrophy Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body ...

  15. Mammary Hypertrophy in an Ovariohysterectomized Cat

    OpenAIRE

    Pukay, B.P.; Stevenson, D.A.

    1983-01-01

    A four year old ovariohysterectomized domestic short-haired cat under treatment for behavioral urine spraying and idiopathic alopecia developed mammary gland hypertrophy following treatment with megestrol acetate. Withdrawal of the progestin and treatment with androgen failed to cause regression of the hypertrophy. The affected mammary gland was surgically excised and recovery was uneventful.

  16. Use of intranasal corticosteroids in adenotonsillar hypertrophy.

    Science.gov (United States)

    Sakarya, E U; Bayar Muluk, N; Sakalar, E G; Senturk, M; Aricigil, M; Bafaqeeh, S A; Cingi, C

    2017-05-01

    This review examined the efficacy of intranasal corticosteroids for improving adenotonsillar hypertrophy. The related literature was searched using PubMed and Proquest Central databases. Adenotonsillar hypertrophy causes mouth breathing, nasal congestion, hyponasal speech, snoring, obstructive sleep apnoea, chronic sinusitis and recurrent otitis media. Adenoidal hypertrophy results in the obstruction of nasal passages and Eustachian tubes, and blocks the clearance of nasal mucus. Adenotonsillar hypertrophy and obstructive sleep apnoea are associated with increased expression of various mediators of inflammatory responses in the tonsils, and respond to anti-inflammatory agents such as corticosteroids. Topical nasal steroids most likely affect the anatomical component by decreasing inspiratory upper airway resistance at the nasal, adenoidal or tonsillar levels. Corticosteroids, by their lympholytic or anti-inflammatory effects, might reduce adenotonsillar hypertrophy. Intranasal corticosteroids reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil and adenoid mixed-cell culture system. Intranasal corticosteroids have been used in adenoidal hypertrophy and adenotonsillar hypertrophy patients, decreasing rates of surgery for adenotonsillar hypertrophy.

  17. Regulation of Cardiac Hypertrophy: the nuclear option

    NARCIS (Netherlands)

    D.W.D. Kuster (Diederik)

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness,

  18. MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy.

    Science.gov (United States)

    Singh, Gurinder Bir; Raut, Satish K; Khanna, Sanskriti; Kumar, Akhilesh; Sharma, Saurabh; Prasad, Rishikesh; Khullar, Madhu

    2017-01-01

    Mitogen-activated protein kinases (MAPKs) (ERK1/2, JNK, and p38) are upregulated in diabetic cardiomyopathy (DCM). Dual-specific phosphatase-1 (DUSP-1) has been reported to regulate the activity of MAPKs in cardiac hypertrophy; however, the role of DUSP-1 in regulating MAPKs activity in DCM is not known. MicroRNAs have been reported to regulate the expression of several genes in hypertrophied failing hearts. However, little is known about the microRNAs regulating DUSP-1 expression in diabetes-related cardiac hypertrophy. In the present study, we investigated the role of DUSP-1 and miR-200c in diabetes-induced cardiac hypertrophy. DCM was induced in Wistar rats by low-dose Streptozotocin high-fat diet for 12 weeks. Cardiac expression of ERK, p-38, JNK, DUSP-1, miR-200c, and hypertrophy markers (ANP and β-MHC) was studied in DCM in control rats and in high-glucose (HG)-treated rat neonatal cardiomyocytes. miR-200c inhibition was performed to validate DUSP-1 as target. A significant increase in phosphorylated ERK, p38, and JNK was observed in DCM model and in HG-treated cardiomyocytes (p 1 was significantly decreased in diabetes group and in HG-treated cardiomyocytes (p 1 causing decreased expression of phosphorylated ERK, p38, and JNK and attenuated cardiomyocyte hypertrophy in HG-treated cardiomyocytes. miR-200c plays a role in diabetes-associated cardiac hypertrophy by modulating expression of DUSP-1.

  19. Cibles moléculaires de la myostatine impliquées dans l'hypertrophie musculaire chez la souris et le bovin

    OpenAIRE

    Chelh, Ilham

    2009-01-01

    Muscle hypertrophy has been extensively studied in meat producing animals. It is generally due to an increase in the total number of fibres, especially, of fast glycolytic fibres and associated to lower collagen content and lower intramuscular fat level. This is favourable to high meat yield and greater tenderness but detrimental to meat flavour. In double-muscled (DM) cattle, a loss-of-function mutation in the myostatin gene (MSTN) is responsible for muscle hypertrophy. This member of Transf...

  20. The role of autophagy in cardiac hypertrophy

    Science.gov (United States)

    Li, Lanfang; Xu, Jin; He, Lu; Peng, Lijun; Zhong, Qiaoqing; Chen, Linxi; Jiang, Zhisheng

    2016-01-01

    Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy. PMID:27084518

  1. The role of autophagy in cardiac hypertrophy.

    Science.gov (United States)

    Li, Lanfang; Xu, Jin; He, Lu; Peng, Lijun; Zhong, Qiaoqing; Chen, Linxi; Jiang, Zhisheng

    2016-06-01

    Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Regression of altitude-produced cardiac hypertrophy.

    Science.gov (United States)

    Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

    1973-01-01

    The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

  3. Multifocal motor neuropathy and muscle hypertrophy.

    Science.gov (United States)

    Geevasinga, N; Day, B; Ng, K

    2013-11-01

    Multifocal motor neuropathy is frequently an asymmetrical neuropathy predominantly affecting the upper limbs. Patients present with weakness, fasciculations and distal muscle wasting. Hypertrophy of muscles is very infrequently reported. We present two cases of multifocal motor neuropathy with upper limb muscle hypertrophy and discuss possible pathophysiological mechanisms. Botulinum toxin may be useful to alleviate cramp. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  4. LIGHT regulates inflamed draining lymph node hypertrophy

    Science.gov (United States)

    Zhu, Mingzhao; Yang, Yajun; Wang, Yugang; Wang, Zhongnan; Fu, Yang-Xin

    2011-01-01

    Lymph node (LN) hypertrophy, the increased cellularity of LNs, is the major indication of the initiation and expansion of the immune response against infection, vaccination, cancer or autoimmunity. The mechanisms underlying LN hypertrophy remain poorly defined. Here, we demonstrate that LIGHT (TNFSF14) is a novel factor essential for LN hypertrophy after CFA immunization. Mechanistically, LIGHT is required for the influx of lymphocytes into but not egress out of LNs. In addition, LIGHT is required for DC migration from the skin to draining LNs. Compared with WT mice, LIGHT−/− mice express lower levels of chemokines in skin and addressins in LN vascular endothelial cells after CFA immunization. We unexpectedly observed that LIGHT from radioresistant rather than radiosensitive cells, likely Langerhans cells, is required for LN hypertrophy. Importantly, antigen-specific T cell responses were impaired in DLN of LIGHT−/− mice, suggesting the importance of LIGHT regulation of LN hypertrophy in the generation of an adaptive immune response. Collectively, our data reveal a novel cellular and molecular mechanism for the regulation of LN hypertrophy and its potential impact on the generation of an optimal adaptive immune response. PMID:21572030

  5. Mechanotransduction pathways in skeletal muscle hypertrophy.

    Science.gov (United States)

    Yamada, André Katayama; Verlengia, Rozangela; Bueno Junior, Carlos Roberto

    2012-02-01

    In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process.

  6. Fat Embolism

    Directory of Open Access Journals (Sweden)

    V. N. Yakovlev

    2013-01-01

    Full Text Available The incidence of fat embolism ranges from 0.5 to 30% in injuries with long and pelvic bone fractures; it also occurs in other diseases and conditions. Moreover, mortality accounts for 3 to 67%. There is still no clear idea on the pathogenesis, prevention, and treatment of fat embolism. This review gives current views on this problem. Key words: fat embolism, poly-trauma.

  7. Hypertrophy of Ligament of Treitz

    Directory of Open Access Journals (Sweden)

    Siddharth P. Dubhashi

    2015-04-01

    Full Text Available Congenital duodenal obstruction commonly occurs due to malrotation, atresia, stenosis and annular pancreas in decreasing order of frequency. This is a case report of a 12 year old male child who presented with complaints of non-projectile vomiting and abdominal distension and pain after meals since 7 years. Barium study showed narrowing of the Duodeno-jejunal(DJ junction due to hypertrophied ligament of Treitz. Exploratory laparotomy revealed a dilated stomach and collapsed bowel loops. There were adhesions at DJ junction and other parts of the small intestine. Adhesiolysis was done. The followup revealed a weight gain of 2 kg. The barium study was repeated which also revealed a normal study. Congenital obstruction of duodeno-jejunal junction due to extrinsic band or due to narrower attachment of ligament of Treitz at duodeno-jejunal flexure is a rare cause of bilious vomiting in the newborn period. A broad attachment of the ligament of Treitz makes a smooth obtuse angle at the duodeno-jejunum junction whereas a narrower insertion creates an acute angle that predisposes to obstruction.Duodenal obstruction may rarely occur in the presence of a normally rotated gut.

  8. Postural control in women with breast hypertrophy

    Directory of Open Access Journals (Sweden)

    Alessandra Ferreira Barbosa

    2012-07-01

    Full Text Available OBJECTIVES: The consequences of breast hypertrophy have been described based on the alteration of body mass distribution, leading to an impact on psychological and physical aspects. The principles of motor control suggest that breast hypertrophy can lead to sensorimotor alterations and the impairment of body balance due to postural misalignment. The aim of this study is to evaluate the postural control of women with breast hypertrophy under different sensory information conditions. METHOD: This cross-sectional study included 14 women with breast hypertrophy and 14 without breast hypertrophy, and the mean ages of the groups were 39 ±15 years and 39±16 years, respectively. A force platform was used to assess the sensory systems that contribute to postural control: somatosensory, visual and vestibular. Four postural conditions were sequentially tested: eyes open and fixed platform, eyes closed and fixed platform, eyes open and mobile platform, and eyes closed and mobile platform. The data were processed, and variables related to the center of pressure were analyzed for each condition. The Kruskal-Wallis test was used to compare the conditions between the groups for the area of center of pressure displacement and the velocity of center of pressure displacement in the anterior-posterior and medial-lateral directions. The alpha level error was set at 0.05. RESULTS: Women with breast hypertrophy presented an area that was significantly higher for three out of four conditions and a higher velocity of center of pressure displacement in the anterior-posterior direction under two conditions: eyes open and mobile platform and eyes closed and mobile platform. CONCLUSIONS: Women with breast hypertrophy have altered postural control, which was demonstrated by the higher area and velocity of center of pressure displacement.

  9. Fat heaps

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Katajainen, Jyrki

    This report is an electronic appendix to our paper \\Fat heaps without regular counters". In that paper we described a new variant of fat heaps that is conceptually simpler and easier to implement than the original version. We also compared the practical performance of this data structure...

  10. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  11. Hypertrophied hearts: what of sevoflurane cardioprotection?

    DEFF Research Database (Denmark)

    Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael

    2009-01-01

    of cardioprotection with anaesthetics remain controversial--in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane...... pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted......-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated...

  12. Protein timing and its effects on muscular hypertrophy and strength in individuals engaged in weight-training

    Directory of Open Access Journals (Sweden)

    Stark Matthew

    2012-12-01

    Full Text Available Abstract The purpose of this review was to determine whether past research provides conclusive evidence about the effects of type and timing of ingestion of specific sources of protein by those engaged in resistance weight training. Two essential, nutrition-related, tenets need to be followed by weightlifters to maximize muscle hypertrophy: the consumption of 1.2-2.0 g protein.kg -1 of body weight, and ≥44-50 kcal.kg-1 of body weight. Researchers have tested the effects of timing of protein supplement ingestion on various physical changes in weightlifters. In general, protein supplementation pre- and post-workout increases physical performance, training session recovery, lean body mass, muscle hypertrophy, and strength. Specific gains, differ however based on protein type and amounts. Studies on timing of consumption of milk have indicated that fat-free milk post-workout was effective in promoting increases in lean body mass, strength, muscle hypertrophy and decreases in body fat. The leucine content of a protein source has an impact on protein synthesis, and affects muscle hypertrophy. Consumption of 3–4 g of leucine is needed to promote maximum protein synthesis. An ideal supplement following resistance exercise should contain whey protein that provides at least 3 g of leucine per serving. A combination of a fast-acting carbohydrate source such as maltodextrin or glucose should be consumed with the protein source, as leucine cannot modulate protein synthesis as effectively without the presence of insulin. Such a supplement post-workout would be most effective in increasing muscle protein synthesis, resulting in greater muscle hypertrophy and strength. In contrast, the consumption of essential amino acids and dextrose appears to be most effective at evoking protein synthesis prior to rather than following resistance exercise. To further enhance muscle hypertrophy and strength, a resistance weight- training program of at least 10–12 weeks

  13. Amlodipine-induced reversible gum hypertrophy

    Directory of Open Access Journals (Sweden)

    Gutch Manish

    2016-01-01

    Full Text Available Gingival hypertrophy is a common manifestation of any pathology affecting gingival and periodontal regions. It commonly follows inflammatory disorders, Vitamin C deficiency, leukemia and due to drugs such as anticonvulsants, immunosuppressants, and calcium channel blockers. Amlodipine is a third generation dihydropyridine derived calcium channel blocker commonly used to treat hypertension. Here, we describe the case of a 45-year-old hypertensive woman who was on amlodipine for 1 year and subsequently developed one of its rarest adverse effects, i.e., gingival hypertrophy.

  14. Reversal of left ventricular hypertrophy by propranolol in ...

    African Journals Online (AJOL)

    Background: Hypertension contributes significantly to the development of left ventricular hypertrophy. Left ventricular hypertrophy is associated with increased incidence of sudden cardiac death. Recognition and management of hypertension is, therefore, imperative. Objective: To establish whether propranolol can reverse ...

  15. Facts about trans fats

    Science.gov (United States)

    ... fat diary with low-fat or nonfat milk, yogurt, and cheese. Alternative Names Trans fatty acids; Partially hydrogenated oils (PHOs); Cholesterol - trans fats; Hyperlipidemia - trans fats; Atherosclerosis - trans fat; ...

  16. Facts about saturated fats

    Science.gov (United States)

    ... fat diary with low-fat or nonfat milk, yogurt, and cheese. Eat more fruits, vegetables, whole grains, and other foods with low or no saturated fat. Alternative Names Cholesterol - saturated fat; Atherosclerosis - saturated fat; Hardening of the ...

  17. Know Your Fats

    Science.gov (United States)

    ... you need. Eating foods containing saturated fat and trans fat causes your body to produce even more, raising ... cholesterol when used in place of saturated and trans fats. Trans Fat Trans fats (or trans fatty acids) ...

  18. Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction

    NARCIS (Netherlands)

    Sung, Miranda M. Y.; Koonen, Debby P. Y.; Soltys, Carrie-Lynn M.; Jacobs, Rene L.; Febbraio, Maria; Dyck, Jason R. B.

    As aging is a significant risk factor for the development of left ventricular hypertrophy and cardiovascular disease, we hypothesized that hearts from middle-aged mice may be more sensitive to the effects of a high fat (HF) diet than hearts from young mice. To investigate this, young (10-12 week

  19. Macro fat and micro fat

    DEFF Research Database (Denmark)

    Li, Yanjun; Gaillard, Jonathan R; McLaughlin, Tracey

    2015-01-01

    in the metabolic syndrome. Changes in fat mass can be induced by altered energy intake or even diet composition. These macroscopic changes must manifest themselves as dynamic adipose cell-size distribution alterations at the microscopic level. The dynamic relationship between these 2 independent measurements...... of body fat is unknown. In this study, we investigate adipose tissue dynamics in response to various isocaloric diet compositions, comparing gender- and insulin sensitivity-dependent differences. A body composition model is used to predict fat mass changes in response to changes in diet composition for 28...... the relative change of fat mass for each diet composition, respectively. We find that adipose cell-size dynamics are associated with different modulations dependent on gender and insulin resistance. Larger turnover and growth/shrinkage rates in insulin resistant individuals suggest they may be more sensitive...

  20. Apoptosis in chronic tonsillitis and tonsillar hypertrophy.

    Science.gov (United States)

    Önal, Merih; Yılmaz, Taner; Bilgiç, Elif; Müftüoğlu, Sevda Fatma; Kuşçu, Oğuz; Günaydın, Rıza Önder

    2015-02-01

    Chronic tonsillitis is the persistent inflammation of the tonsillar tissue that occurs due to recurrent, acute or subclinical infection. The recurrent and chronic inflammation of palatine tonsils sometimes results in hypertrophy. Apoptosis provides an important balance between lymphocytes in tonsillar lymphoid tissue. The aim of this study is to investigate the apoptosis in tonsillar diseases. 43 patients with chronic tonsilitis and tonsillar hypertrophy underwent tonsillectomy. The specimens were examined immunohistochemically for apoptosis. Tonsils were assembled into groups according to their size. Specimens were compared for their apoptotic cell count. The apoptosis difference between the tonsil size groups is not statistically significant (p>0.05). However, when the study group was divided into two at age 6, the difference was not statistically significant for patients at and below 6 years of age; but, the difference was statistically significant for patients above 6 years of age (ptonsil tissue (intrafollicular, interfollicular, subepithelial and intraepithelial) between tonsil size stages and between chronic tonsillitis and tonsillar hypertrophy groups revealed no statistical significance (p>0.05). There was a statistically significant positive correlation between intrafollicular and interfollicular, interfollicular and intraepithelial & subepithelial and intraepithelial areas (ptonsil tissue. The association of apoptosis with tonsillar hypertrophy seemed to be age-dependent. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Tripartite motif 32 prevents pathological cardiac hypertrophy.

    Science.gov (United States)

    Chen, Lijuan; Huang, Jia; Ji, Yanxiao; Zhang, Xiaojing; Wang, Pixiao; Deng, Keqiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2016-05-01

    TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. © 2016 The Author(s).

  2. Left ventricular hypertrophy : virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, S; Sharma, UC; Pinto, YM

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca2+ homeostasis, there

  3. Left ventricular hypertrophy, geometric patterns and clinical ...

    African Journals Online (AJOL)

    Background: Left ventricular hypertrophy can be due to various reasons including hypertension. It constitutes an increased cardiovascular risk. Various left ventricular geometric patterns occur in hypertension and may affect the cardiovascular risk profile of hypertensive subjects. Methods: One hundred and eighty eight ...

  4. Compensatory Hypertrophy After Living Donor Nephrectomy.

    Science.gov (United States)

    Chen, K W; Wu, M W F; Chen, Z; Tai, B C; Goh, Y S B; Lata, R; Vathsala, A; Tiong, H Y

    2016-04-01

    Previous studies have shown that kidney volume enhances the estimation of glomerular filtration rate (eGFR) in kidney donors. This study aimed to describe the phenomenon of compensatory hypertrophy after donor nephrectomy as measured on computerized tomographic (CT) scans. An institutional Domain Specific Review Board (DSRB)-approved study involved approaching kidney donors to have a follow up CT scan from 6 months to 1 year after surgery; 29 patients participated; 55% were female. Clinical chart review was performed, and the patient's remaining kidney volume was measured before and after surgery based on CT scans. eGFR was determined with the use of the Modification of Diet in Renal Disease equation. Mean parenchymal volume of the remaining kidney for this population (mean age, 44.3 ± 8.5 y) was 204.7 ± 82.5 cc before surgery and 250.5 ± 113.3 cc after donor nephrectomy. Compensatory hypertrophy occurred in 79.3% of patients (n = 23). Mean increase in remaining kidney volume was 22.4 ± 23.2% after donor nephrectomy in healthy individuals. Over a median follow-up of 52.9 ± 19.8 months, mean eGFR was 68.9 ± 12.4 mL/min/1.73 m(2), with 24.1% of patients (n = 7) in chronic kidney disease grade 3. Absolute and relative change in kidney volume was not associated with sex, race, surgical approach, or background of hypertension (P = NS). There was a trend of decreased hypertrophy with increasing age (P = .5; Spearman correlation, -0.12). In healthy kidney donors, compensatory hypertrophy of the remaining kidney occurs in 79.3% of the patients, with an average increment of about 22.4%. Older patients may have a blunted compensatory hypertrophy response after surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The effects of fatty acid composition on cardiac hypertrophy and function in mouse models of diet-induced obesity.

    Science.gov (United States)

    Nguyen, Son; Shao, Dan; Tomasi, Loreta C; Braun, Alyssa; de Mattos, Ana Barbosa Marcondes; Choi, Yong Seon; Villet, Outi; Roe, Nathan; Halterman, Carliana R; Tian, Rong; Kolwicz, Stephen C

    2017-08-01

    High-fat diets (HFDs) are used frequently to study the development of cardiac dysfunction in animal models of obesity and diabetes. However, impairment in systolic function, often reported as declining ejection fraction, may not consistently occur in a given time frame which could be contributable to a variety of factors within the experimental design. One major factor may be the amounts of saturated and unsaturated fatty acids (FAs) that are present in the diet. To determine whether the FA content and composition were critical determinants in the development of cardiac dysfunction in response to high-fat feeding, we fed adult, male mice Western diet (45% fat, 60% saturated), Surwit diet (60% fat, 90% saturated), milk-fat-based diet (60% fat, 60% saturated) or high-fat Western diet (HFWD, 60% fat, 32% saturated) for 12 weeks. We report that neither the amount of total fat nor the ratio of saturated to unsaturated FAs in the diets differentially affects body weight and adiposity in mice. In addition, no evidence of systolic dysfunction is present after 12 weeks. Interestingly, the HFWD, with equal parts saturated, monounsaturated and polyunsaturated FAs, induces mild cardiac hypertrophy and diastolic dysfunction after 12 weeks, which coincides with elevated serum levels of arachidonic acid. Our results suggest that the dietary FA content and composition may be a primary determinant of diastolic, but not systolic, dysfunction in animal models of diet-induced obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. DJ-1 activates autophagy in the repression of cardiac hypertrophy.

    Science.gov (United States)

    Xue, Ruicong; Jiang, Jingzhou; Dong, Bin; Tan, Weiping; Sun, Yu; Zhao, Jingjing; Chen, Yili; Dong, Yugang; Liu, Chen

    2017-11-01

    Cardiac hypertrophy is the risk factor of heart failure when the heart is confronted with pressure overload or neurohumoral stimuli. Autophagy, a conserved degradative pathway, is one of the important mechanisms involved in the regulation of cardiac hypertrophy. DJ-1 is a traditional anti-oxidative protein and emerging evidence suggested that DJ-1 might modulate autophagy. However, the regulation of autophagy by DJ-1 in the process of cardiac hypertrophy remains unknown. In our study, we firstly discovered that the expression of DJ-1declined in the process of pressure overload cardiac hypertrophy, and its alteration was parallel with the impairment of autophagy. Furthermore, we proved that DJ-1 knockout mice exhibited a more hypertrophied phenotype than wildtype mice in cardiac hypertrophy which indicated that DJ-1 is responsible for the repression of cardiac hypertrophy. Furthermore, DJ-1 knockout significantly exacerbated pulmonary edema due to cardiac hypertrophy. In the process of cardiac hypertrophy, DJ-1 knockout significantly impaired autophagy activation and enhanced mTORC1 and mTORC2 phosphorylation were found. Similarly, our in vitro study proved that DJ-1 overexpression ameliorated phenylephrine (PE)-induced cardiac hypertrophy and promoted autophagy activation. Taken together, DJ-1 might repress both pressure overload and PE-induced cardiac hypertrophy via the activation of autophagy. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [Benign prostatic hypertrophy and prostate cancer].

    Science.gov (United States)

    Mourey, Loïc; Doumerc, Nicolas; Gaudin, Clément; Gérard, Stéphane; Balardy, Laurent

    2014-01-01

    Prostatic diseases are extremely common, especially in older men. Amongst them, benign prostatic hypertrophy may affect significantly the quality of life of patients by the symptoms it causes. It requires appropriate care. Prostate cancer is the second most common cancer in men after lung cancer and the fifth leading cause of cancer deaths in the world. It affects preferentially older men. An oncogeriatric approach is required for personalised care.

  8. Breast Hypertrophy, Reduction Mammaplasty, and Body Image.

    Science.gov (United States)

    Fonseca, Cristiane Costa; Veiga, Daniela Francescato; Garcia, Edgard da Silva; Cabral, Isaías Vieira; de Carvalho, Monique Maçais; de Brito, Maria José Azevedo; Ferreira, Lydia Masako

    2018-02-07

    Body image dissatisfaction is one of the major factors that motivate patients to undergo plastic surgery. However, few studies have associated body satisfaction with reduction mammaplasty. The aim of this study was to evaluate the impact of breast hypertrophy and reduction mammaplasty on body image. Breast hypertrophy patients, with reduction mammaplasty already scheduled between June 2013 and December 2015 (mammaplasty group, MG), were prospectively evaluated through the body dysmorphic disorder examination (BDDE), body investment scale (BIS), and breast evaluation questionnaire (BEQ55) tools. Women with normal-sized breasts were also evaluated as study controls (normal-sized breast group, NSBG). All the participants were interviewed at the initial assessment and after six months. Data were analyzed before and after six months. Each group consisted of 103 women. The MG group had a significant improvement in BDDE, BIS, and BEQ55 scores six months postoperatively (P ≤ 0.001 for the three instruments), whereas the NSBG group showed no alteration in results over time (P = 0.876; P = 0.442; and P = 0.184, respectively). In the intergroup comparison it was observed that the MG group began to invest more in the body, similarly to the NSBG group, and surpassed the level of satisfaction and body image that the women of the NSBG group had after the surgery. Reduction mammaplasty promoted improvement in body image of women with breast hypertrophy.

  9. Fat Analysis

    Science.gov (United States)

    Min, David B.; Ellefson, Wayne C.

    Lipids, proteins, and carbohydrates constitute the principal structural components of foods. Lipids are a group of substances that, in general, are soluble in ether, chloroform, or other organic solvents but are sparingly soluble in water. However, there exists no clear scientific definition of a lipid, primarily due to the water solubility of certain molecules that fall within one of the variable categories of food lipids (1). Some lipids, such as triacylglycerols, are very hydrophobic. Other lipids, such as di- and monoacylglycerols, have both hydrophobic and hydrophilic moieties in their molecules and are soluble in relatively polar solvents (2). Short-chain fatty acids such as C1-C4 are completely miscible in water and insoluble in nonpolar solvents (1). The most widely accepted definition is based on solubility as previously stated. While most macromolecules are characterized by common structural features, the designation of "lipid" being defined by solubility characteristics is unique to lipids (2). Lipids comprise a broad group of substances that have some common properties and compositional similarities (3). Triacylglycerols are fats and oils that represent the most prevalent category of the group of compounds known as lipids. The terms lipids, fats, and oils are often used interchangeably. The term "lipid" commonly refers to the broad, total collection of food molecules that meet the definition previously stated. Fats generally refer to those lipids that are solid at room temperature and oils generally refer to those lipids that are liquid at room temperature. While there may not be an exact scientific definition, the US Food and Drug Administration (FDA) has established a regulatory definition for nutrition labeling purposes. The FDA has defined total fat as the sum of fatty acids from C4 to C24, calculated as triglycerides. This definition provides a clear path for resolution of any nutrition labeling disputes.

  10. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  11. Choroidal thickness evaluation in paediatric patients with adenotonsillar hypertrophy.

    Science.gov (United States)

    Yenigun, A; Elbay, A; Hafiz, A M; Ozturan, O

    2017-09-01

    To investigate choroidal thickness using enhanced-depth imaging optical coherence tomography in paediatric patients with adenotonsillar hypertrophy, with comparison to healthy children, three months after adenotonsillectomy. The patients were assigned to three groups: an adenotonsillar hypertrophy group, an adenotonsillectomy group and a healthy control group. In all groups, subfoveal, temporal and nasal choroidal thickness measurements were taken. In the subfoveal, temporal and nasal regions, choroidal tissue was found to be significantly thinner in adenotonsillar hypertrophy children than healthy children (p = 0.012, p = 0.027 and p = 0.020). The subfoveal and temporal choroidal thickness measurements of adenotonsillar hypertrophy group cases were significantly decreased compared to those in the adenotonsillectomy group (p = 0.038 and p = 0.048). There was a significant association between decreased choroidal thickness and adenotonsillar hypertrophy. Adenotonsillar hypertrophy may play an important role in decreased choroidal thickness.

  12. Western diet increases cardiac ceramide content in healthy and hypertrophied hearts.

    Science.gov (United States)

    Butler, T J; Ashford, D; Seymour, A-M

    2017-11-01

    Obesity and cardiac left ventricular hypertrophy (LVH) are recognised independent risk factors in the development of heart failure (HF). However, the combination of these factors may exacerbate the onset of cardiovascular disease by mechanisms as yet unclear. LVH leads to significant cellular remodelling, including alterations in metabolism which may result in an inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The aim of the study was to determine the impact of dietary manipulation on cardiac metabolism in the obese and hypertrophied heart. LVH was induced via aortic constriction (AC) in an experimental model of cardiac hypertrophy and animals subjected to 9 weeks of dietary manipulation with either a standard, high fat, or a sucrose containing Western-style diet (SD, HFD and WD, respectively). This latter diet resulted in accelerated weight gain in both LVH/AC and control animals. LVH was greater in AC animals fed a WD, and both control and AC animals from this diet showed a significant reduction in cardiac fatty acid oxidation and increased triacylglycerol content. Ceramide content was significantly increased in the WD groups, with no additional effect of LVH. Comparison with a model of HF induced by exposure to Doxorubicin and WD showed exacerbated remodelling of cardiac ceramide species leading to increased C16 and C18 content. These findings highlight the inappropriate accumulation and re-distribution of cardiac ceramide species in a diet-induced model of obesity and LVH, potentially increasing susceptibility to cell death. The combination of increased fat and sugar leads to greater pathological remodelling and may explain why this diet pattern is consistently linked with poor cardiovascular outcomes. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

  13. Cardiac Hypertrophy: An Introduction to Molecular and Cellular Basis

    OpenAIRE

    Samak, Mostafa; Fatullayev, Javid; Sabashnikov, Anton; Zeriouh, Mohamed; Schmack, Bastian; Farag, Mina; Popov, Aron-Frederik; Dohmen, Pascal M.; Choi, Yeong-Hoon; Wahlers, Thorsten; Weymann, Alexander

    2016-01-01

    Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is complex and multifactorial, as it touches on several cellular and molecular systems. Understanding the molecular background of cardiac hypertrophy is essential in order to protect the myocardium from pathological remodeling, or slow down the destined progression to heart failure. In this review we highlight the most important mo...

  14. Disseminated cysticercosis with huge muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Bandyopadhyay Debabrata

    2009-01-01

    Full Text Available Cysticercosis is caused by cysticercus cellulose, which is the larva of Taenia solium , the pork tapeworm. The larvae are carried in the blood stream after penetrating the walls of the alimentary tract and they lodge in different tissues like the skin, skeletal muscles, brain, fundus and heart, to cause disseminated cysticercosis. Cases of disseminated cysticercosis have rarely been reported in the literature. They may inhabit the muscles and cause muscular hypertrophy, which, at times, may assume gross proportions. Morbidity is usually caused by the involvement of the central nervous system or the eyes.

  15. Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K; Wachtell, K

    2005-01-01

    Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy...

  16. Compensatory renal hypertrophy following uninephrectomy is calcineurin-independent.

    Science.gov (United States)

    Williams, Clintoria R; Wynne, Brandi M; Walker, Makeeva; Hoover, Robert S; Gooch, Jennifer L

    2014-12-01

    Calcineurin is a calcium-dependent phosphatase that is involved in many cellular processes including hypertrophy. Inhibition or genetic loss of calcineurin blocks pathological cardiac hypertrophy and diabetic renal hypertrophy. However, calcineurin does not appear to be involved in physiological cardiac hypertrophy induced by exercise. The role of calcineurin in a compensatory, non-pathological model of renal hypertrophy has not been tested. Therefore, in this study, we examined activation of calcineurin and the effect of calcineurin inhibition or knockout on compensatory hypertrophy following uninephrectomy (UNX). UNX induces ~15% increase in the size of the remaining kidney; the data show no change in the generation of reactive oxygen species (ROS), Nox4 or transforming growth factor-β expression confirming the model as one of compensatory hypertrophy. Next, analyses of the remaining kidney reveal that total calcineurin activity is increased, and, to a lesser extent, transcriptional activity of the calcineurin substrate nuclear factor of activated T cell is up-regulated following UNX. However, inhibition of calcineurin with cyclosporine failed to prevent compensatory renal hypertrophy. Likewise, hypertrophy was comparable to WT in mice lacking either isoform of the catalytic subunit of calcineurin (CnAα-/- or CnAβ-/-). In conclusion, similar to its role in the heart, calcineurin is required for pathological but not compensatory renal hypertrophy. This separation of signalling pathways could therefore help further define key factors necessary for pathological hypertrophy including diabetic nephropathy. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  17. Glucose Transporters in Cardiac Metabolism and Hypertrophy

    Science.gov (United States)

    Shao, Dan; Tian, Rong

    2016-01-01

    The heart is adapted to utilize all classes of substrates to meet the high-energy demand, and it tightly regulates its substrate utilization in response to environmental changes. Although fatty acids are known as the predominant fuel for the adult heart at resting stage, the heart switches its substrate preference toward glucose during stress conditions such as ischemia and pathological hypertrophy. Notably, increasing evidence suggests that the loss of metabolic flexibility associated with increased reliance on glucose utilization contribute to the development of cardiac dysfunction. The changes in glucose metabolism in hypertrophied hearts include altered glucose transport and increased glycolysis. Despite the role of glucose as an energy source, changes in other nonenergy producing pathways related to glucose metabolism, such as hexosamine biosynthetic pathway and pentose phosphate pathway, are also observed in the diseased hearts. This article summarizes the current knowledge regarding the regulation of glucose transporter expression and translocation in the heart during physiological and pathological conditions. It also discusses the signaling mechanisms governing glucose uptake in cardiomyocytes, as well as the changes of cardiac glucose metabolism under disease conditions. PMID:26756635

  18. Mechanotransduction in cardiac hypertrophy and failure.

    Science.gov (United States)

    Lyon, Robert C; Zanella, Fabian; Omens, Jeffrey H; Sheikh, Farah

    2015-04-10

    Cardiac muscle cells have an intrinsic ability to sense and respond to mechanical load through a process known as mechanotransduction. In the heart, this process involves the conversion of mechanical stimuli into biochemical events that induce changes in myocardial structure and function. Mechanotransduction and its downstream effects function initially as adaptive responses that serve as compensatory mechanisms during adaptation to the initial load. However, under prolonged and abnormal loading conditions, the remodeling processes can become maladaptive, leading to altered physiological function and the development of pathological cardiac hypertrophy and heart failure. Although the mechanisms underlying mechanotransduction are far from being fully elucidated, human and mouse genetic studies have highlighted various cytoskeletal and sarcolemmal structures in cardiac myocytes as the likely candidates for load transducers, based on their link to signaling molecules and architectural components important in disease pathogenesis. In this review, we summarize recent developments that have uncovered specific protein complexes linked to mechanotransduction and mechanotransmission within the sarcomere, the intercalated disc, and at the sarcolemma. The protein structures acting as mechanotransducers are the first step in the process that drives physiological and pathological cardiac hypertrophy and remodeling, as well as the transition to heart failure, and may provide better insights into mechanisms driving mechanotransduction-based diseases. © 2015 American Heart Association, Inc.

  19. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

    African Journals Online (AJOL)

    elevation of hypoxia inducible factor (HIF), which in turn leads to increases in levels of VEGF and other angiogenic factors. This adaptive response delays progression from pathological cardiac hypertrophy to heart failure. In early cardiac hypertrophy, stability of HIF-1 promotes glycolysis, which improves glucose utilization ...

  20. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas

    2013-01-01

    at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern......The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one...... of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy....

  1. Saturated fat (image)

    Science.gov (United States)

    Saturated fat can raise blood cholesterol and can put you at risk for heart disease and stroke. You should ... limit any foods that are high in saturated fat. Sources of saturated fat include whole-milk dairy ...

  2. Effects of weight gain and weight loss on regional fat distribution1234

    Science.gov (United States)

    Singh, Prachi; Somers, Virend K; Romero-Corral, Abel; Sert-Kuniyoshi, Fatima H; Pusalavidyasagar, Snigdha; Davison, Diane E

    2012-01-01

    Background: Normal-weight adults gain lower-body fat via adipocyte hyperplasia and upper-body subcutaneous (UBSQ) fat via adipocyte hypertrophy. Objectives: We investigated whether regional fat loss mirrors fat gain and whether the loss of lower-body fat is attributed to decreased adipocyte number or size. Design: We assessed UBSQ, lower-body, and visceral fat gains and losses in response to overfeeding and underfeeding in 23 normal-weight adults (15 men) by using dual-energy X-ray absorptiometry and abdominal computed tomography scans. Participants gained ∼5% of weight in 8 wk and lost ∼80% of gained fat in 8 wk. We measured abdominal subcutaneous and femoral adipocyte sizes and numbers after weight gain and loss. Results: Volunteers gained 3.1 ± 2.1 (mean ± SD) kg body fat with overfeeding and lost 2.4 ± 1.7 kg body fat with underfeeding. Although UBSQ and visceral fat gains were completely reversed after 8 wk of underfeeding, lower-body fat had not yet returned to baseline values. Abdominal and femoral adipocyte sizes, but not numbers, decreased with weight loss. Decreases in abdominal adipocyte size and UBSQ fat mass were correlated (ρ = 0.76, P = 0.001), as were decreases in femoral adipocyte size and lower-body fat (ρ = 0.49, P = 0.05). Conclusions: UBSQ and visceral fat increase and decrease proportionately with a short-term weight gain and loss, whereas a gain of lower-body fat does not relate to the loss of lower-body fat. The loss of lower-body fat is attributed to a reduced fat cell size, but not number, which may result in long-term increases in fat cell numbers. PMID:22760561

  3. Effects of weight gain and weight loss on regional fat distribution.

    Science.gov (United States)

    Singh, Prachi; Somers, Virend K; Romero-Corral, Abel; Sert-Kuniyoshi, Fatima H; Pusalavidyasagar, Snigdha; Davison, Diane E; Jensen, Michael D

    2012-08-01

    Normal-weight adults gain lower-body fat via adipocyte hyperplasia and upper-body subcutaneous (UBSQ) fat via adipocyte hypertrophy. We investigated whether regional fat loss mirrors fat gain and whether the loss of lower-body fat is attributed to decreased adipocyte number or size. We assessed UBSQ, lower-body, and visceral fat gains and losses in response to overfeeding and underfeeding in 23 normal-weight adults (15 men) by using dual-energy X-ray absorptiometry and abdominal computed tomography scans. Participants gained ∼5% of weight in 8 wk and lost ∼80% of gained fat in 8 wk. We measured abdominal subcutaneous and femoral adipocyte sizes and numbers after weight gain and loss. Volunteers gained 3.1 ± 2.1 (mean ± SD) kg body fat with overfeeding and lost 2.4 ± 1.7 kg body fat with underfeeding. Although UBSQ and visceral fat gains were completely reversed after 8 wk of underfeeding, lower-body fat had not yet returned to baseline values. Abdominal and femoral adipocyte sizes, but not numbers, decreased with weight loss. Decreases in abdominal adipocyte size and UBSQ fat mass were correlated (ρ = 0.76, P = 0.001), as were decreases in femoral adipocyte size and lower-body fat (ρ = 0.49, P = 0.05). UBSQ and visceral fat increase and decrease proportionately with a short-term weight gain and loss, whereas a gain of lower-body fat does not relate to the loss of lower-body fat. The loss of lower-body fat is attributed to a reduced fat cell size, but not number, which may result in long-term increases in fat cell numbers.

  4. Cardiac hypertrophy in mice expressing unphosphorylatable phospholemman.

    Science.gov (United States)

    Boguslavskyi, Andrii; Pavlovic, Davor; Aughton, Karen; Clark, James E; Howie, Jacqueline; Fuller, William; Shattock, Michael J

    2014-10-01

    Elevation of intracellular Na in the failing myocardium contributes to contractile dysfunction, the negative force-frequency relationship, and arrhythmias. Although phospholemman (PLM) is recognized to form the link between signalling pathways and Na/K pump activity, the possibility that defects in its regulation contribute to elevation of intracellular Na has not been investigated. Our aim was to test the hypothesis that the prevention of PLM phosphorylation in a PLM(3SA) knock-in mouse (in which PLM has been rendered unphosphorylatable) will exacerbate cardiac hypertrophy and cellular Na overload. Testing this hypothesis should determine whether changes in PLM phosphorylation are simply bystander effects or are causally involved in disease progression. In wild-type (WT) mice, aortic constriction resulted in hypophosphorylation of PLM with no change in Na/K pump expression. This under-phosphorylation of PLM occurred at 3 days post-banding and was associated with a progressive decline in Na/K pump current and elevation of [Na]i. Echocardiography, morphometry, and pressure-volume (PV) catheterization confirmed remodelling, dilation, and contractile dysfunction, respectively. In PLM(3SA) mice, expression of Na/K ATPase was increased and PLM decreased such that net Na/K pump current under quiescent conditions was unchanged (cf. WT myocytes); [Na(+)]i was increased and forward-mode Na/Ca exchanger was reduced in paced PLM(3SA) myocytes. Cardiac hypertrophy and Na/K pump inhibition were significantly exacerbated in banded PLM(3SA) mice compared with banded WT. Decreased phosphorylation of PLM reduces Na/K pump activity and exacerbates Na overload, contractile dysfunction, and adverse remodelling following aortic constriction in mice. This suggests a novel therapeutic target for the treatment of heart failure. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  5. Overexpression of microRNA-99a Attenuates Cardiac Hypertrophy

    Science.gov (United States)

    Li, Ran; Bai, Jian; Ding, Liang; Gu, Rong; Wang, Lian; Xu, Biao

    2016-01-01

    Pathological cardiomyocyte hypertrophy is associated with significantly increased risk of heart failure, one of the leading medical causes of mortality worldwide. MicroRNAs are known to be involved in pathological cardiac remodeling. However, whether miR-99a participates in the signaling cascade leading to cardiac hypertrophy is unknown. To evaluate the role of miR-99a in cardiac hypertrophy, we assessed the expression of miR-99a in hypertrophic cardiomyocytes induced by isoprenaline (ISO)/angiotensin-II (Ang II) and in mice model of cardiac hypertrophy induced by transverse aortic constriction (TAC). Expression of miR-99a was evaluated in these hypertrophic cells and hearts. We also found that miR-99a expression was highly correlated with cardiac function of mice with heart failure (8 weeks after TAC surgery). Overexpression of miR-99a attenuated cardiac hypertrophy in TAC mice and cellular hypertrophy in stimuli treated cardiomyocytes through down-regulation of expression of mammalian target of rapamycin (mTOR). These results indicate that miR-99a negatively regulates physiological hypertrophy through mTOR signaling pathway, which may provide a new therapeutic approach for pressure-overload heart failure. PMID:26914935

  6. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy

    Science.gov (United States)

    Putinski, Charis; Abdul-Ghani, Mohammad; Stiles, Rebecca; Brunette, Steve; Dick, Sarah A.; Fernando, Pasan; Megeney, Lynn A.

    2013-01-01

    Cardiomyocyte hypertrophy is the cellular response that mediates pathologic enlargement of the heart. This maladaptation is also characterized by cell behaviors that are typically associated with apoptosis, including cytoskeletal reorganization and disassembly, altered nuclear morphology, and enhanced protein synthesis/translation. Here, we investigated the requirement of apoptotic caspase pathways in mediating cardiomyocyte hypertrophy. Cardiomyocytes treated with hypertrophy agonists displayed rapid and transient activation of the intrinsic-mediated cell death pathway, characterized by elevated levels of caspase 9, followed by caspase 3 protease activity. Disruption of the intrinsic cell death pathway at multiple junctures led to a significant inhibition of cardiomyocyte hypertrophy during agonist stimulation, with a corresponding reduction in the expression of known hypertrophic markers (atrial natriuretic peptide) and transcription factor activity [myocyte enhancer factor-2, nuclear factor kappa B (NF-κB)]. Similarly, in vivo attenuation of caspase activity via adenoviral expression of the biologic effector caspase inhibitor p35 blunted cardiomyocyte hypertrophy in response to agonist stimulation. Treatment of cardiomyocytes with procaspase 3 activating compound 1, a small-molecule activator of caspase 3, resulted in a robust induction of the hypertrophy response in the absence of any agonist stimulation. These results suggest that caspase-dependent signaling is necessary and sufficient to promote cardiomyocyte hypertrophy. These results also confirm that cell death signal pathways behave as active remodeling agents in cardiomyocytes, independent of inducing an apoptosis response. PMID:24101493

  7. Overexpression of microRNA-99a Attenuates Cardiac Hypertrophy.

    Science.gov (United States)

    Li, Qiaoling; Xie, Jun; Wang, Bingjian; Li, Ran; Bai, Jian; Ding, Liang; Gu, Rong; Wang, Lian; Xu, Biao

    2016-01-01

    Pathological cardiomyocyte hypertrophy is associated with significantly increased risk of heart failure, one of the leading medical causes of mortality worldwide. MicroRNAs are known to be involved in pathological cardiac remodeling. However, whether miR-99a participates in the signaling cascade leading to cardiac hypertrophy is unknown. To evaluate the role of miR-99a in cardiac hypertrophy, we assessed the expression of miR-99a in hypertrophic cardiomyocytes induced by isoprenaline (ISO)/angiotensin-II (Ang II) and in mice model of cardiac hypertrophy induced by transverse aortic constriction (TAC). Expression of miR-99a was evaluated in these hypertrophic cells and hearts. We also found that miR-99a expression was highly correlated with cardiac function of mice with heart failure (8 weeks after TAC surgery). Overexpression of miR-99a attenuated cardiac hypertrophy in TAC mice and cellular hypertrophy in stimuli treated cardiomyocytes through down-regulation of expression of mammalian target of rapamycin (mTOR). These results indicate that miR-99a negatively regulates physiological hypertrophy through mTOR signaling pathway, which may provide a new therapeutic approach for pressure-overload heart failure.

  8. Regression of Pathological Cardiac Hypertrophy: Signaling Pathways and Therapeutic Targets

    Science.gov (United States)

    Hou, Jianglong; Kang, Y. James

    2012-01-01

    Pathological cardiac hypertrophy is a key risk factor for heart failure. It is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. The progression of pathological cardiac hypertrophy has long been considered as irreversible. However, recent clinical observations and experimental studies have produced evidence showing the reversal of pathological cardiac hypertrophy. Left ventricle assist devices used in heart failure patients for bridging to transplantation not only improve peripheral circulation but also often cause reverse remodeling of the geometry and recovery of the function of the heart. Dietary supplementation with physiologically relevant levels of copper can reverse pathological cardiac hypertrophy in mice. Angiogenesis is essential and vascular endothelial growth factor (VEGF) is a constitutive factor for the regression. The action of VEGF is mediated by VEGF receptor-1, whose activation is linked to cyclic GMP-dependent protein kinase-1 (PKG-1) signaling pathways, and inhibition of cyclic GMP degradation leads to regression of pathological cardiac hypertrophy. Most of these pathways are regulated by hypoxia-inducible factor. Potential therapeutic targets for promoting the regression include: promotion of angiogenesis, selective enhancement of VEGF receptor-1 signaling pathways, stimulation of PKG-1 pathways, and sustention of hypoxia-inducible factor transcriptional activity. More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming. PMID:22750195

  9. Dietary lipids: less fat or best fat?

    Directory of Open Access Journals (Sweden)

    Chardigny Jean-Michel

    2013-03-01

    Full Text Available Obesity and overweight occurrence is growing around the word. This is often considered as a consequence of high fat diets, and some recommendations encourage ‘‘light’’ diets, including low fat intake. However, most trials with low fat intake do not demonstrate any benefit and could be worse than low carbohydrate diets. The key role of insulin could explain that eating fat do not make body fat. On the other hand, several unbalanced fatty acid intake are reported, i.e. saturated/mononunsaturated fatty acids and w6/w3 polyunsaturated fatty acids. Thus, fat intake could be improved in this respect. Moreover, the molecular and supramolecular structures of fat in food are new challenges to address in order to ameliorate the recommendations for healthy diets.

  10. Cardiac Hypertrophy: An Introduction to Molecular and Cellular Basis

    Science.gov (United States)

    Samak, Mostafa; Fatullayev, Javid; Sabashnikov, Anton; Zeriouh, Mohamed; Schmack, Bastian; Farag, Mina; Popov, Aron-Frederik; Dohmen, Pascal M.; Choi, Yeong-Hoon; Wahlers, Thorsten; Weymann, Alexander

    2016-01-01

    Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is complex and multifactorial, as it touches on several cellular and molecular systems. Understanding the molecular background of cardiac hypertrophy is essential in order to protect the myocardium from pathological remodeling, or slow down the destined progression to heart failure. In this review we highlight the most important molecular aspects of cardiac hypertrophic growth in light of the currently available published research data. PMID:27450399

  11. Ageing of the bony orbit is a major cause of age-related intraorbital fat herniation.

    Science.gov (United States)

    Kim, Junhyung; Park, Sang Woo; Choi, Jaehoon; Jeong, Woonhyeok; Lee, Seongwon

    2017-11-28

    We evaluated the relationship between infraorbital fat herniation and age-related changes in the bony orbit and orbital fat density using computed tomography. Two hundred and sixty-five patients were enrolled (60 patients were evaluated for changes in the bony orbit and 205 for changes in orbital fat density). Five measurements using parasagittal sections and one measurement using three-dimensional images were obtained. Intraorbital fat herniation length was positively correlated with orbital rim inclination. Lowering of the inferior orbital rim, which is connected to the orbicularis retaining ligament, tear trough ligament and orbital septum, can cause mechanical stretching of the lower eyelid and may contribute to infraorbital fat herniation. A strong and significant negative correlation was observed between orbital fat density and age, indicating that existing orbital fat can accommodate an enlargement in bony orbit volume without orbital fat hyperplasia/hypertrophy. In other words, an increased orbital fat volume may be a by-product of the adaptation of orbital fat to changes in bony orbit volume. Mechanical stretching of the lower eyelid due to ageing of the bony orbit and weakening of the lower eyelid due to age-related factors such as dermal/fat/muscle atrophy and loss of muscle tone can together result in anterior drooping of the lower eyelid. Therefore, age-related changes in the bony orbit contribute to intraorbital fat herniation. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Dietary habits of preschool aged children with tonsillar hypertrophy, pre- and post-operatively.

    Science.gov (United States)

    Gkouskou, K K; Vlastos, I M; Hajiioannou, I; Hatzaki, I; Houlakis, M; Fragkiadakis, G A

    2010-12-01

    Tonsillectomy has been reported to have a positive effect on weight gain of children with tonsillar hypertrophy. This effect may be related to better respiration or/and feeding, immunological or metabolic factors. In this study we analyse the effect of tonsillectomy on the dietary habits of children. Dietary habits of thirty 4-6 years old children were assessed before the operation and six months after it, using 24 hours dietary-recalls. In parallel, dietary habits of eighteen healthy children of the same age were assessed using the same method. Children with tonsillar hypertrophy were receiving greater amounts of daily calories overall from sugar products, soft drinks and edible fats (p = 0.01, t = 2.673). Post-operatively, they increased the calories they were consuming daily and consumed even greater amounts of these food (p < 0.001, t = 3.527) in relation to the control group, gaining weight significantly (p = 0.043). Parents should be aware of a possible weight increase after tonsillectomy which can be related to an over-consumption of products like candies and soft drinks.

  13. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

    Science.gov (United States)

    Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2016-11-11

    The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

  14. Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice.

    Science.gov (United States)

    Chang, Cherng-Shyang; Tsai, Pei-Jane; Sung, Junne-Ming; Chen, Ju-Yi; Ho, Li-Chun; Pandya, Kumar; Maeda, Nobuyo; Tsai, Yau-Sheng

    2014-02-01

    Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg(+/-)) mice, but not in mice defective for ligand binding (Pparg(P465L/+)). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Reliability of hypertrophy of the contralateral testis in prediction of ...

    African Journals Online (AJOL)

    Reliability of hypertrophy of the contralateral testis in prediction of the status of impalpable testis. Rafik Shalaby, Ahmad Alshamy, Mohamad Abd-Alrazek, Samir Gouda, Mohamad Mahfouz, Mohamad Shahin, Sabri Moussa, Sayed Elhady, Hassan Algallad ...

  16. [Behavior research of allergic rhinitis with adenoid hypertrophy in children].

    Science.gov (United States)

    Jing, Yunlong; Hu, Binya; Huang, Jing; Zhao, Sijun; Tao, Lihua; Peng, Xiangyue

    2012-06-01

    To investigate the behavior difference of allergic rhinitis with adenoid hypertrophy between study group and control group. One hundred and seventeen children diagnosed as allergic rhinitis with adenoid hypertrophy were enrolled in our study were divided into study group and control group. Forty-two children treated with local steroid nasal spray for two to three months and antihistamine were control group. Seventy-five children treated with endoscopic adenoidectomy and drug treatment were study group; All children' parents were inquired for their clinical presentation. No distinctive differences were found between the two groups (P > 0.05) in adenoid hypertrophy, accompanying nasal problems and clinical questionnaire scoring. Significant statistical distinction were found (P breathing, and recurrent respiratory tract infection between the two groups after three-month follow up. Endoscopic adenoidectomy should be taken into account for allergic rhinitis with adenoid hypertrophy in children. Adenoidectomy would be useful for the improvement of behavior symptoms.

  17. Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth

    National Research Council Canada - National Science Library

    Jo, Junghyo; Gavrilova, Oksana; Pack, Stephanie; Jou, William; Mullen, Shawn; Sumner, Anne E; Cushman, Samuel W; Periwal, Vipul

    2009-01-01

    Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity...

  18. Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs.

    Directory of Open Access Journals (Sweden)

    Jihan Xia

    Full Text Available A long-term high-energy diet affects human health and leads to obesity and metabolic syndrome in addition to cardiac steatosis and hypertrophy. Ectopic fat accumulation in the heart has been demonstrated to be a risk factor for heart disorders, but the molecular mechanism of heart disease remains largely unknown. Bama miniature pigs were fed a high-fat, high-sucrose diet (HFHSD for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased body weight (2.73-fold, P<0.01, insulin level (4.60-fold, P<0.01, heart weight (1.82-fold, P<0.05 and heart volume (1.60-fold, P<0.05 compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. Microarray analyses revealed that 1,022 genes were significantly differentially expressed (P<0.05, ≥1.5-fold change, including 591 up-regulated and 431 down-regulated genes in the HFHSD group relative to the control group. KEGG analysis indicated that the observed heart disorder involved the signal transduction-related MAPK, cytokine, and PPAR signaling pathways, energy metabolism-related fatty acid and oxidative phosphorylation signaling pathways, heart function signaling-related focal adhesion, axon guidance, hypertrophic cardiomyopathy and actin cytoskeleton signaling pathways, inflammation and apoptosis pathways, and others. Quantitative RT-PCR assays identified several important differentially expressed heart-related genes, including STAT3, ACSL4, ATF4, FADD, PPP3CA, CD74, SLA-8, VCL, ACTN2 and FGFR1, which may be targets of further research. This study shows that a long-term, high-energy diet induces obesity, cardiac steatosis, and hypertrophy and provides insights into the molecular mechanisms of hypertrophy and fatty heart to facilitate further research.

  19. β-Hydroxy-β-methylbutyrate (HMβ supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway

    Directory of Open Access Journals (Sweden)

    Pimentel Gustavo D

    2011-02-01

    Full Text Available Abstract β-Hydroxy-β-methylbutyrate (HMβ supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e.g., fat and liver have not been examined. The purpose of this study was to evaluate the effects of HMβ supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HMβ (320 mg/kg body weight or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HMβ supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.

  20. Malondialdehyde in benign prostate hypertrophy: a useful marker?

    OpenAIRE

    Rosaria Alba Merendino; Francesco Salvo; Antonella Saija; Giuseppe Di Pasquale; Antonio Tomaino; Paola Lucia Minciullo; Giuseppe Fraccica; Sebastiano Gangemi

    2003-01-01

    Benign prostate hypertrophy (BPH) is the most common benign tumor in men due to obstruction of the urethra and, finally, uremia. Malondialdehyde (MDA) is a product derived from peroxidation of polyunsaturated fatty acids and related esters. Evaluation of MDA in serum represents a non-invasive biomarker of oxidative stress. Prostate-specific antigen (PSA) is a sensitive marker for prostatic hypertrophy and cancer. We analyzed MDA serum levels to evaluate the oxidative stress in BPH. To this en...

  1. Time course of gene expression during mouse skeletal muscle hypertrophy

    Science.gov (United States)

    Lee, Jonah D.; England, Jonathan H.; Esser, Karyn A.; McCarthy, John J.

    2013-01-01

    The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy. PMID:23869057

  2. Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.

    Science.gov (United States)

    Saito, Takeyuki; Yokota, Kazuya; Kobayakawa, Kazu; Hara, Masamitsu; Kubota, Kensuke; Harimaya, Katsumi; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Matsumoto, Yoshihiro; Doi, Toshio; Shiba, Keiichiro; Nakashima, Yasuharu; Okada, Seiji

    2017-01-01

    Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.

  3. Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy.

    Science.gov (United States)

    Xiao, Yang; Yang, Zheng; Wu, Qing-Qing; Jiang, Xiao-Han; Yuan, Yuan; Chang, Wei; Bian, Zhou Yan; Zhu, Jin Xiu; Tang, Qi-Zhu

    2017-11-01

    Lack of effective anti-cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti-hypertrophy and anti-fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti-hypertrophy and -fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross-sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B-mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3-MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B-mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899-3910, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Raf-mediated cardiac hypertrophy in adult Drosophila

    Science.gov (United States)

    Yu, Lin; Daniels, Joseph; Glaser, Alex E.; Wolf, Matthew J.

    2013-01-01

    SUMMARY In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK) signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr) RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for

  5. The possibilities to improve muscle strength and hypertrophy

    OpenAIRE

    Chramosta, Roman

    2014-01-01

    The name of this dissertation: The possibilities to improve muscle strength and hypertrophy in fitness centers. The aim of this dissertation: Searches on chronic zhe possibility of hypertrophy, muscular strength in fitness centers and summary of right and effective training in fitness centers. Method: The method in this dissertaiton is summary of technical data correct and effective workout. Use of survey questions, I found a level of and satisfaction at the fitness centers and how much time ...

  6. Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2006-09-01

    WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and FAT4 are Cadherin superfamily members homologous to Drosophila Fat, functioning as a positive regulator of PCP in the Drosophila wing. Complete coding sequence (CDS) for human FAT1 (NM_005245.3) and FAT2 (NM_001447.1) are available, while artificial CDS for human FAT3 (XM_926199 and XM_936538) and partial CDS for FAT4 (NM_024582.2). Here, complete CDS of human FAT3 and FAT4 were determined by using bioinformatics and human intelligence (Humint). FAT3 gene, consisting of 26 exons, encoded a 4557-aa protein with extracellular 33 Cadherin repeats, one Laminin G (LamG) domain and two EGF domains. FAT4 gene encoded a 4924-aa protein with extracellular 34 Cadherin repeats, two LamG domains and three EGF domains. Cytoplasmic VCSVxPxLP and SDYxS motifs were identified as novel motifs conserved among FAT1, FAT2 and FAT3 orthologs. Domain architecture comparison and phylogenetic analysis revealed that FAT1, FAT2 and FAR3 were divergent from FAT4. FAT1-MTNR1A locus at 4q35.2 and FAT3-MTNR1B locus at 11q14.3-q21 were paralogous regions within the human genome. FAT1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, lung cancer and brain tumors. FAT2 mRNA was expressed in infant brain, cerebellum, gastric cancer, pancreatic cancer, ovarian cancer, esophageal cancer, skin squamous cell carcinoma, head and neck cancer. FAT3 mRNA was expressed in ES cells, primitive neuroectoderm, fetal brain, infant brain, adult neural tissues and prostate. FAT4 mRNA was expressed in fetal brain, infant brain, brain tumor and colorectal cancer. FAT family members were revealed to be targets of systems

  7. Resolution of enuresis after adenotsillectomy in children with adenotonsillar hypertrophy

    Directory of Open Access Journals (Sweden)

    Mohammad Naeimi

    2008-06-01

    Full Text Available Introduction: Most of the upper airway obstructions are caused by adenotonsillar hypertrophy. Prevalence of nocturnal enuresis in children accompanied with upper airway obstruction is reported in 8-47% of cases. Considering this fact that adenotonsillar hypertrophy is curable by adenotonsilletomy, in present study the effect of this operation in treatment of children with adenotonsillar hypertrophy has been investigated by comparing the rate of nocturnal enuresis pre and post operation. Materials and Methods: During a period of 18 months, all children referred to otorhinolaryngology department of Ghaem hospital suffering from nocturnal enuresis and adenotonsillar hypertrophy have been surveyed. The patients were evaluated for improvement in nocturnal enuresis after adenotosillectomy for a period of three months. Results: Theaverage age of patients was 6.8 years. 63.8% of children had primary nocturnal enuresis and 36.2% secondary nocturnal enuresis. One month after adenotonsillectomy in 88% of children nocturnal enuresis was completely cured. Using Friedman test we revealed that there was no significant difference in second and third month in comparison with first month. Complete improvement was observed in patients with secondary nocturnal enuresis. Between severity of adenotonsillar hypertrophy and improvement in nocturnal enuresis only in patients with adenoid hypertrophy the result was significant (P

  8. Network Reconstruction and Systems Analysis of Cardiac Myocyte Hypertrophy Signaling*

    Science.gov (United States)

    Ryall, Karen A.; Holland, David O.; Delaney, Kyle A.; Kraeutler, Matthew J.; Parker, Audrey J.; Saucerman, Jeffrey J.

    2012-01-01

    Cardiac hypertrophy is managed by a dense web of signaling pathways with many pathways influencing myocyte growth. A quantitative understanding of the contributions of individual pathways and their interactions is needed to better understand hypertrophy signaling and to develop more effective therapies for heart failure. We developed a computational model of the cardiac myocyte hypertrophy signaling network to determine how the components and network topology lead to differential regulation of transcription factors, gene expression, and myocyte size. Our computational model of the hypertrophy signaling network contains 106 species and 193 reactions, integrating 14 established pathways regulating cardiac myocyte growth. 109 of 114 model predictions were validated using published experimental data testing the effects of receptor activation on transcription factors and myocyte phenotypic outputs. Network motif analysis revealed an enrichment of bifan and biparallel cross-talk motifs. Sensitivity analysis was used to inform clustering of the network into modules and to identify species with the greatest effects on cell growth. Many species influenced hypertrophy, but only a few nodes had large positive or negative influences. Ras, a network hub, had the greatest effect on cell area and influenced more species than any other protein in the network. We validated this model prediction in cultured cardiac myocytes. With this integrative computational model, we identified the most influential species in the cardiac hypertrophy signaling network and demonstrate how different levels of network organization affect myocyte size, transcription factors, and gene expression. PMID:23091058

  9. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy

    Science.gov (United States)

    Abel, E. Dale; Doenst, Torsten

    2011-01-01

    Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences. PMID:21257612

  10. The role of hormones in muscle hypertrophy.

    Science.gov (United States)

    Fink, Julius; Schoenfeld, Brad Jon; Nakazato, Koichi

    2018-02-01

    Anabolic-androgenic steroids (AAS) and other hormones such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been shown to increase muscle mass in patients suffering from various diseases related to muscle atrophy. Despite known side-effects associated with supraphysiologic doses of such drugs, their anabolic effects have led to their widespread use and abuse by bodybuilders and athletes such as strength athletes seeking to improve performance and muscle mass. On the other hand, resistance training (RT) has also been shown to induce significant endogenous hormonal (testosterone (T), GH, IGF-1) elevations. Therefore, some bodybuilders employ RT protocols designed to elevate hormonal levels in order to maximize anabolic responses. In this article, we reviewed current RT protocol outcomes with and without performance enhancing drug usage. Acute RT-induced hormonal elevations seem not to be directly correlated with muscle growth. On the other hand, supplementation with AAS and other hormones might lead to supraphysiological muscle hypertrophy, especially when different compounds are combined.

  11. Non‐coding RNAs in cardiac hypertrophy

    Science.gov (United States)

    Ottaviani, Lara

    2017-01-01

    Abstract Heart failure is one of the largest contributors to disease burden and healthcare outflow in the Western world. Despite significant progress in the treatment of heart failure, disease prognosis remains very poor, with the only curative therapy still being heart transplantation. To counteract the current situation, efforts have been made to better understand the underlying molecular pathways in the progression of cardiac disease towards heart failure, and to link the disease to novel therapeutic targets such as non‐coding RNAs. The non‐coding part of the genome has gained prominence over the last couple of decades, opening a completely new research field and establishing different non‐coding RNAs species as fundamental regulators of cellular functions. Not surprisingly, their dysregulation is increasingly being linked to pathology, including to cardiac disease. Pre‐clinically, non‐coding RNAs have been shown to be of great value as therapeutic targets in pathological cardiac remodelling and also as diagnostic/prognostic biomarkers for heart failure. Therefore, it is to be expected that non‐coding RNA‐based therapeutic strategies will reach the bedside in the future and provide new and more efficient treatments for heart failure. Here, we review recent discoveries linking the function and molecular interactions of non‐coding RNAs with the pathophysiology of cardiac hypertrophy and heart failure. PMID:28233323

  12. Body Fat Distribution and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Nicola Abate

    2013-06-01

    Full Text Available The burden of obesity has increased globally over the last few decades and its association with insulin resistance and related cardio-metabolic problems have adversely affected our ability to reduce population morbidity and mortality. Traditionally, adipose tissue in the visceral fat depot has been considered a major culprit in the development of insulin resistance. However, there is a growing body of evidence supporting the role of subcutaneous truncal/abdominal adipose tissue in the development of insulin resistance. There are significant differences in the functional characteristics of subcutaneous abdominal/truncal vs. intraabdominal vs. gluteo-femoral fat depots. More recently, mounting evidence has been supporting the role of adipose tissue function in the development of metabolic complications independent of adipose tissue volume or distribution. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger a vicious cycle of inflammation leading to subcutaneous adipose tissue dysfunction and ectopic fat deposition. Therapeutic lifestyle change continues to be the most important intervention in clinical practice to improve adipose tissue function and avoid development of insulin resistance and related cardio-metabolic complications.

  13. The relation between childhood obesity and adenotonsillar hypertrophy.

    Science.gov (United States)

    Daar, Ghaniya; Sarı, Kamran; Gencer, Zeliha Kapusuz; Ede, Hüseyin; Aydın, Reha; Saydam, Levent

    2016-02-01

    Childhood obesity is a common and significant public health problem all over the world. As a well-known fact obese children have an increased risk of obesity-associated comorbidities, including obstructive sleep apnea, diabetes, and cardiovascular disorders at an earlier age compared to their normal weight peers. They also have an increased risk of poor self-esteem, greater body dissatisfaction, and increased peer teasing that lead to a lower health-related quality of life. While the presence of adenoid hypertrophy and increased rate of obstructive sleep apnea frequently co-exists in majority of cases. We have limited knowledge about the effect of adenotonsillar hypertrophy on development of childhood obesity. In this study, we aimed to investigate the association between obesity, presence of adenotonsillar hypertrophy and the quality of life parameters in obese children as measured by the OSA-18 quality of life questionnaire. Fifty obese children aged between 3 and 18 years and 50 age- and gender-matched otherwise children were enrolled to the study. All subjects were routinely examined by the otolaryngologist before enrollment. The size of adenoid hypertrophy was measured using lateral cephalometric radiographs. The tonsils were also graded using the schema recommended by Brodsky et al. We used OSA-18 questionnaires to evaluate the subjects' quality of life issues. We found, 34 % of obese group had tonsillar hypertrophy while the rate was 6 % in control group. Similarly 16 % of obese group had tonsillar hypertrophy compared to only 4 % in non-obese group. It was also noted that total OSA-18 scores of obese group were significantly higher than those of non-obese group. In subgroup analysis of obese group, total OSA-18 score of obese subjects with either adenoid and/or tonsillar hypertrophy was significantly higher than that of obese subjects without adenoid or tonsillar hypertrophy. As the related literature suggests that the impact of adenotonsillar size on OSA

  14. Mitochondrial Reprogramming Induced by CaMKIIδ Mediates Hypertrophy Decompensation

    Science.gov (United States)

    Westenbrink, B. Daan; Ling, Haiyun; Divakaruni, Ajit; Gray, Charles B. B.; Zambon, Alexander C.; Dalton, Nancy D.; Peterson, Kirk L.; Gu, Yusu; Matkovich, Scot J.; Murphy, Anne; Miyamoto, Shigeki; Dorn, Gerald W.; Brown, Joan Heller

    2015-01-01

    Rationale Sustained activation of Gq signaling during pressure overload causes cardiac hypertrophy that ultimately progresses to dilated cardiomyopathy. The molecular events that drive hypertrophy decompensation are incompletely understood. Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) is activated downstream of Gq and overexpression of Gq and CaMKIIδ recapitulates hypertrophy decompensation. Objective To determine whether CaMKIIδ contributes to hypertrophy decompensation provoked by Gq. Methods and Results Compared to Gαq transgenic (Gq) mice, compound Gq/CaMKIIδ knockout (KO) (Gq/KO) mice developed a similar degree of cardiac hypertrophy but exhibited significantly improved left ventricular function, less cardiac fibrosis and cardiomyocyte apoptosis, and fewer ventricular arrhythmias. Markers of oxidative stress were elevated in mitochondria from Gq vs. WT mice and respiratory rates were lower; these changes in mitochondrial function were restored by CaMKIIδ deletion. Gq-mediated increases in mitochondrial oxidative stress, compromised membrane potential and cell death were recapitulated in NRVMs infected with constitutively active Gq and attenuated by CaMKII inhibition. Deep RNA sequencing revealed altered expression of 41 mitochondrial genes in Gq hearts, with normalization of ~40% of these genes by CaMKIIδ deletion. Uncoupling protein 3 (UCP3) was markedly downregulated in Gq or by Gq expression in NRVMs and reversed by CaMKIIδ deletion or inhibition, as was Peroxisome proliferator-activated receptor alpha (PPAR-α). The protective effects of CaMKIIδ inhibition on ROS generation and cell death were abrogated by knock down of UCP3. Conversely, restoration of UCP3 expression attenuated ROS generation and cell death induced by CaMKIIδ. Our in vivo studies further demonstrated that pressure overload induced decreases in PPAR-α and UCP3, increases in mitochondrial protein oxidation, and hypertrophy decompensation which were attenuated by Ca

  15. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  16. Facts about monounsaturated fats

    Science.gov (United States)

    ... health. How Monounsaturated Fats Affect Your Health Monounsaturated fats are good for your health in several ways: They can help lower your LDL (bad) cholesterol level. Cholesterol is a soft, waxy substance ...

  17. Dietary fat and children

    Science.gov (United States)

    Some fat in the diet is needed for normal growth and development. However, many conditions such as obesity, heart disease, and diabetes are linked to eating too much fat or eating the wrong types of ...

  18. Verapamil induced ventricular hypertrophy in conscious dogs.

    Science.gov (United States)

    French, W J; Garner, D; Adomian, G E; Averill, W; Laks, M M

    1989-08-01

    Verapamil is used clinically in the treatment of various cardiac diseases including hypertrophic cardiomyopathy. Its long term effects on ventricular mass are not well known. In 11 conscious dogs heart rate, aortic and left ventricular pressures, cardiac output, a methoxamine induced stress ventricular function test and left ventriculography were performed. These variables were measured prior to and following a mean 7.2 month infusion of verapamil at 0.005 or 0.01 mg.kg-1.min-1 using a subcutaneously implanted pump. Resting haemodynamic variables and left ventricular ejection fraction [60(SD 6) v 55(6)%] were unchanged between baseline and chronic verapamil studies, but the slope of the methoxamine induced stress ventricular function test decreased from 3.9(0.8) to 2.1 (1.3). After verapamil was discontinued the mean slope of the stress ventricular function test returned to the baseline 4.0(1.7). Total ventricular weight increased 22% from 176.1(17.5) g.m-2 in controls to 215.6(29.5) g.m-2 (p less than 0.01) in the verapamil animals. The right ventricular weight increased 25% from 46(5.9) to 57.6(9.1) g.m-2 (p less than 0.01); the septum weight increased 26% from 42.5(4.1) to 53.7(7.2) g.m-2 (p less than 0.001); and the left ventricular free wall weight increased 19% from 87.4(9.8) to 103.9(15.7) g.m-2 (p less than 0.01). The increase in ventricular weights was not due to fibrosis or oedema since hydroxyproline contents and wet/dry ratios were not increased. In conclusion, a chronic infusion of verapamil in conscious dogs caused no change in resting haemodynamic variables but produced reversible depression of stress ventricular function and biventricular and septal hypertrophy.

  19. Trans Fat Now Listed With Saturated Fat and Cholesterol

    Science.gov (United States)

    ... Trans Fat Now Listed With Saturated Fat and Cholesterol Share Tweet Linkedin Pin it More sharing options ... I Do About Saturated Fat, Trans Fat, and Cholesterol? When comparing foods, look at the Nutrition Facts ...

  20. Dietary fats explained

    Science.gov (United States)

    ... and fatty meats. Some vegetable oils, such as coconut, palm, and palm kernel oil, also contain saturated fats. These fats are solid at room temperature. A diet high in saturated fat increases cholesterol buildup in your arteries (blood vessels). Cholesterol is ...

  1. Fats and Your Child

    Science.gov (United States)

    ... Healthy fats are a vital part of a child’s diet, and they should not be excessively limited or banned. For young kids, especially, fat and cholesterol play important roles in brain development. And for those under 2 years old, fat ...

  2. AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress.

    Science.gov (United States)

    Ma, Yuedong; Huang, Huiling; Jiang, Jingzhou; Wu, Lingling; Lin, Chunxi; Tang, Anli; Dai, Gang; He, Jiangui; Chen, Yili

    2016-06-10

    AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress. Copyright © 2016. Published by Elsevier Inc.

  3. Developmental delays in preschool children with adenotonsillar hypertrophy.

    Science.gov (United States)

    Soylu, Erkan; Soylu, Nusret; Polat, Cahit; Sakallıoğlu, Öner; Uçur, Ömer; Bozdoğan, Gökçe

    2016-01-01

    This study aims to investigate the effects of adenotonsillar hypertrophy on general development, as well as fine and gross motor capabilities, social communication, and language development in children with adenotonsillar hypertrophy by applying the Denver Developmental Screening Test-II. The study included 30 patients (12 boys, 18 girls; mean age 53.3±12.2 months; range 32 to 72 months) who were indicated for adenotonsillectomy due to adenotonsillar hypertrophy between February 2013 and July 2013. The control group comprised 30 children participants (12 boys, 18 girls; mean age 53.1±12.8 months; range 32 to 72 months) with no adenotonsillectomy indication. All participants included in the study were performed routine physical examination, flexible fiberoptic nasopharyngoscopy, and tympanometry. Brodsky scale and fiberendoscopic findings were used to categorize tonsil and adenoid sizes, respectively. Following ear, nose, and throat evaluation, a psychologist conducted Denver Developmental Screening Test-II in all participants blindly. Adenotonsillar hypertrophy patients had higher abnormal levels of general development (c2=7.13, p=0.028). Although patients and controls had similar levels of fine motor, gross motor, and personal-social development levels, there was a statistically borderline difference between them in terms of language development (t=1.82, p=0.074). The possibility of adenotonsillar hypertrophy should definitely be considered in children with delayed general and language developments.

  4. Phosphorylation of ribosomal protein S6 mediates compensatory renal hypertrophy

    Science.gov (United States)

    Xu, Jinxian; Chen, Jianchun; Dong, Zheng; Meyuhas, Oded; Chen, Jian-Kang

    2014-01-01

    The molecular mechanism underlying renal hypertrophy and progressive nephron damage remains poorly understood. Here we generated congenic ribosomal protein S6 (rpS6) knockin mice expressing non-phosphorylatable rpS6 and found that uninephrectomy-induced renal hypertrophy was significantly blunted in these knockin mice. Uninephrectomy-induced increases in cyclin D1 and decreases in cyclin E in the remaining kidney were attenuated in the knockin mice compared to their wild-type littermates. Uninephrectomy induced rpS6 phosphorylation in the wild type mice; however, no rpS6 phosphorylation was detected in uninephrectomized or sham-operated knockin mice. Nonetheless, uninephrectomy stimulated comparable 4E-BP1 phosphorylation in both knockin and wild type mice, indicating that mTORC1 was still activated in the knockin mice. Moreover, the mTORC1 inhibitor rapamycin prevented both rpS6 and 4E-BP1 phosphorylation, significantly blunted uninephrectomy-induced renal hypertrophy in wild type mice, but did not prevent residual renal hypertrophy despite inhibiting 4E-BP1 phosphorylation in uninephrectomized knockin mice. Thus, both genetic and pharmacological approaches unequivocally demonstrate that phosphorylated rpS6 is a downstream effector of the mTORC1-S6K1 signaling pathway mediating renal hypertrophy. Hence, rpS6 phosphorylation facilitates the increase in cyclin D1 and decrease in cyclin E1 that underlie the hypertrophic nature of uninephrectomy-induced kidney growth. PMID:25229342

  5. Neurogenic muscle hypertrophy in a 12-year-old girl.

    Science.gov (United States)

    Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip

    2017-01-01

    Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  6. [Hypertrophy of labia minora--pathomorphology and surgical treatment].

    Science.gov (United States)

    Kruk-Jeromin, Julia; Zieliński, Tomasz

    2010-04-01

    Hypertrophy of labia minora is a variant of normal anatomy. The enlargement can be unilateral or bilateral and is sometimes asymmetric. Hypertrophy of the labia minora may be attributed to mechanical irritation and endocrine diseases. Labia minora longer than 5 cm is a functional and aesthetic problem for many women. Surgical treatment is performed at the request of the patient and based on surgical reduction of labia minora. The goal of this paper is to present our own experiences in labia minora reduction. Twenty-one patients with labia minora hypertrophy aged from 18 to 35, were operated. Hypertrophy was bilateral in all cases but asymmetrical in 5. We have observed that labia majora were smaller than normally and even after labioplasty did not contact in the midline. We performed elliptical resection of the protuberant segment of the hypertrophic labium. We obtained good aesthetic and functional results. All patients were fully satisfied with the outcome. Hypertrophy of labia minora is not a pathologic condition but rather a variant of normal anatomy. Indication of the operation is psychical and functional discomfort. Elliptical resection of the protuberant tissue is a safe method of treatment.

  7. Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Slava Malatiali

    2008-01-01

    Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

  8. Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes

    Science.gov (United States)

    Sanjabi, Bahram; Dashty, Monireh; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Rahimi, Mehran; Vinciguerra, Manlio; van Rooij, Felix; Al-Lahham, Saad; Sheedfar, Fareeba; van Kooten, Theo G.; Spek, C. Arnold; Rowshani, Ajda T.; van der Want, Johannes; Klaassen, Rene; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-03-01

    Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional. Insulin concentrations and release are fat mass- and LDs-dependent respectively. Fat reduction mediated by bariatric surgery repairs obesity-associated T2D. The expression of genes, like PCSK1 (proinsulin conversion enzyme), GCG (Glucagon), GPLD1, CD38 and NNAT, involved in insulin regulation/release were differentially expressed in pancreas and adipose tissue (AT). INS (insulin) and GCG expression reduced in human AT-T2D as compared to AT-control, but remained unchanged in pancreas in either state. Insulin levels (mRNA/protein) were higher in AT derived from prediabetes BB rats with destructed pancreatic β-cells and controls than pancreas derived from the same rats respectively. Insulin expression in 10 human primary cell types including adipocytes and macrophages is an evidence for extrapancreatic insulin-producing cells. The data suggest a crosstalk between AT and pancreas to fine-tune energy metabolic system or may minimize the metabolic damage during diabetes. This study opens new avenues towards T2D therapy with a great impact on public health.

  9. Muscle hypertrophy in prepubescent tennis players: a segmentation MRI study.

    Science.gov (United States)

    Sanchis-Moysi, Joaquin; Idoate, Fernando; Serrano-Sanchez, Jose A; Dorado, Cecilia; Calbet, Jose A L

    2012-01-01

    To asses if tennis at prepubertal age elicits the hypertrophy of dominant arm muscles. The volume of the muscles of both arms was determined using magnetic resonance imaging (MRI) in 7 male prepubertal tennis players (TP) and 7 non-active control subjects (CG) (mean age 11.0 ± 0.8 years, Tanner 1-2). TP had 13% greater total muscle volume in the dominant than in the contralateral arm. The magnitude of inter-arm asymmetry was greater in TP than in CG (13 vs 3%, Pmuscle volumes in both groups (P = 0.25), after accounting for height as covariate. In TP, dominant deltoid (11%), forearm supinator (55%) and forearm flexors (21%) and extensors (25%) were hypertrophied compared to the contralateral arm (Pmuscle was bigger than its contralateral homonimous (63%, Pmuscle volumes in dominant compared to the non-dominant arm, likely due to selectively hypertrophy of the loaded muscles.

  10. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

    Science.gov (United States)

    Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-08-01

    Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

  11. Extra-Esophageal Pepsin from Stomach Refluxate Promoted Tonsil Hypertrophy.

    Science.gov (United States)

    Kim, Jin Hyun; Jeong, Han-Sin; Kim, Kyung Mi; Lee, Ye Jin; Jung, Myeong Hee; Park, Jung Je; Kim, Jin Pyeong; Woo, Seung Hoon

    2016-01-01

    Gastroesophageal reflux is associated with numerous pathologic conditions of the upper aerodigestive tract. Gastric pepsin within reflux contributes to immunologic reactions in the tonsil. In this study, we aimed to find the relationships between pepsin and tonsillar hypertrophy. We explored the notion whether tonsillar hypertrophy was due to pepsin-mediated gastric reflux in tonsil hypertrophy. Fifty-four children with tonsil hypertrophy and 30 adults with tonsillitis were recruited before surgical treatment. Blood and tonsil tissues from each patient were harvested for analysis of changes in lymphocyte and macrophage numbers coupled with histological and biochemical analysis. Pepsin was expressed at different levels in tonsil tissues from each tonsillar hypertrophy. Pepsin-positive cells were found in the crypt epithelium, surrounding the lymphoid follicle with developing fibrosis, and also surrounding the lymphoid follicle that faced the crypt. And also, pepsin staining was well correlated with damaged tonsillar squamous epithelium and TGF-β1 and iNOS expression in the tonsil section. In addition, pepsin and TGF-β1-positive cells were co-localized with CD68-positive cells in the crypt and surrounding germinal centers. In comparison of macrophage responsiveness to pepsin, peripheral blood mononuclear cells (PBMNCs) were noticeably larger in the presence of activated pepsin in the child group. Furthermore, CD11c and CD163-positive cells were significantly increased by activated pepsin. However, this was not seen for the culture of PBMNCs from the adult group. The lymphocytes and monocytes are in a highly proliferative state in the tonsillar hypertrophy and associated with increased expression of pro-inflammatory factors as a result of exposure to stomach reflux pepsin.

  12. Relationship between coronary artery size and ventricular hypertrophy.

    Science.gov (United States)

    Liau, C S; Chen, M F; Chen, W J; Lee, C M; Peng, J Y; Lee, Y T

    1989-02-01

    The relationship between coronary blood flow and ventricular hypertrophy has been studied in animal models. But, this relationship in the human body is scarcely evaluated. In this study we measured coronary arterial sizes by coronary arteriograms and correlated them with ventricular hypertrophy. Patients who underwent cardiac catheterization and coronary arteriography and showed no significant coronary arterial lesions were included in this study. There were 131 patients, 75 men and 56 women, with a mean age of 53 +/- 10 years (S.D.). After evaluation with electrocardiograms, echocardiograms and left ventriculograms these patients were divided into 4 groups: (1) the non-hypertrophy (NVH) group, 50 cases; (2) the left ventricular hypertrophy (LVH) group, 38 cases; (3) the right ventricular hypertrophy (RVH) group, 23 cases; and (4) the biventricular hypertrophy (BVH) group, 20 cases. The proximal portion of the 3 major coronary arteries and the left main stem were measured from coronary arteriograms with the catheter tip as a size reference. The results showed that the left main stem was larger than the 3 major coronary arteries in the NVH, LVH and BVH groups. But in the RVH group, the left main stem was not significantly larger than the right coronary artery. In all 4 groups the left circumflex coronary artery was the smallest while the left anterior descending coronary artery and the right coronary artery were similar in size. Patients with LVH showed dilatation of all 3 left coronary measurements (left main stem, left anterior descending coronary artery and left circumflex coronary artery) as compared with the NVH patients and the RVH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Supra-physiological dose of testosterone induces pathological cardiac hypertrophy.

    Science.gov (United States)

    Pirompol, Prapawadee; Teekabut, Vassana; Weerachatyanukul, Wattana; Bupha-Intr, Tepmanas; Wattanapermpool, Jonggonnee

    2016-04-01

    Testosterone and androgenic anabolic steroids have been misused for enhancement of physical performance despite many reports on cardiac sudden death. Although physiological level of testosterone provided many regulatory benefits to human health, including the cardiovascular function, supra-physiological levels of the hormone induce hypertrophy of the heart with unclear contractile activation. In this study, dose- and time-dependent effects of high-testosterone treatment on cardiac structure and function were evaluated. Adult male rats were divided into four groups of testosterone treatment for 0, 5, 10, and 20 mg/kg BW for 4, 8, or 12 weeks. Increases in both percentage heart:body weight ratio and cardiomyocyte cross-sectional area in representing hypertrophy of the heart were significantly shown in all testosterone-treated groups to the same degree. In 4-week-treated rats, physiological cardiac hypertrophy was apparent with an upregulation of α-MHC without any change in myofilament contractile activation. In contrast, pathological cardiac hypertrophy was observed in 8- and 12-week testosterone-treated groups, as indicated by suppression of myofilament activation and myocardial collagen deposition without transition of MHC isoforms. Only in 12-week testosterone-treated group, eccentric cardiac hypertrophy was demonstrated with unaltered myocardial stiffness, but significant reductions in the phosphorylation signals of ERK1/2 and mTOR. Results of our study suggest that the outcome of testosterone-induced cardiac hypertrophy is not dose dependent but is rather relied on the factor of exposure to duration in inducing maladaptive responses of the heart. © 2016 Society for Endocrinology.

  14. Congenital hypertrophy of multiple intrinsic muscles of the foot.

    Science.gov (United States)

    Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

    2014-12-01

    Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

  15. Focal adhesion kinase signaling in cardiac hypertrophy and failure

    Directory of Open Access Journals (Sweden)

    K.G. Franchini

    2009-01-01

    Full Text Available Focal adhesion kinase (FAK is a broadly expressed tyrosine kinase implicated in cellular functions such as migration, growth and survival. Emerging data support a role for FAK in cardiac development, reactive hypertrophy and failure. Data reviewed here indicate that FAK plays a critical role at the cellular level in the responses of cardiomyocytes and cardiac fibroblasts to biomechanical stress and to hypertrophic agonists such as angiotensin II and endothelin. The signaling mechanisms regulated by FAK are discussed to provide insight into its role in the pathophysiology of cardiac hypertrophy and failure.

  16. Hypertrophy of the acetabulo-cristal buttress in Homo sapiens.

    Science.gov (United States)

    Rader, W T; Peters, C R

    1993-10-01

    In the early 1970s, excavation at the King site, a contact period Mississippian village in northwest Georgia, yielded the skeletal remains of a robust male (King 65) possessing marked hypertrophy of the acetabulo-cristal buttress. The buttress is morphologically similar to that of Plio-Pleistocene Homo but it is accompanied by an anatomically modern degree of thickening of the gluteal table of the ilium. Although the degree of cortical thickness of the gluteal table of the ilium is apparently species-specific, hypertrophy of the acetabulo-cristal buttress is developmental and may be expressed in all species of Homo.

  17. Association of heart failure hospitalizations with combined electrocardiography and echocardiography criteria for left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Gerdts, Eva; Okin, Peter M; Boman, Kurt

    2012-01-01

    The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain.......The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain....

  18. Through thick and thin: A circulating growth factor inhibits age-related cardiac hypertrophy

    OpenAIRE

    McPherron, Alexandra C.

    2013-01-01

    In an intriguing new study, Loffredo et al., report that joining the circulation of old mice with that of young mice reduces age-related cardiac hypertrophy. They also found that the growth factor GDF11 is a circulating negative regulator of cardiac hypertrophy which suggests that raising GDF11 levels may be useful to treat cardiac hypertrophy associated with aging.

  19. Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy

    Directory of Open Access Journals (Sweden)

    Karoulas Takis

    2007-03-01

    Full Text Available Abstract Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II, but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest; and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient, but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM.

  20. Muscle hypertrophy in prepubescent tennis players: a segmentation MRI study.

    Directory of Open Access Journals (Sweden)

    Joaquin Sanchis-Moysi

    Full Text Available PURPOSE: To asses if tennis at prepubertal age elicits the hypertrophy of dominant arm muscles. METHODS: The volume of the muscles of both arms was determined using magnetic resonance imaging (MRI in 7 male prepubertal tennis players (TP and 7 non-active control subjects (CG (mean age 11.0 ± 0.8 years, Tanner 1-2. RESULTS: TP had 13% greater total muscle volume in the dominant than in the contralateral arm. The magnitude of inter-arm asymmetry was greater in TP than in CG (13 vs 3%, P<0.001. The dominant arm of TP was 16% greater than the dominant arm of CG (P<0.01, whilst non-dominant arms had similar total muscle volumes in both groups (P = 0.25, after accounting for height as covariate. In TP, dominant deltoid (11%, forearm supinator (55% and forearm flexors (21% and extensors (25% were hypertrophied compared to the contralateral arm (P<0.05. In CG, the dominant supinator muscle was bigger than its contralateral homonimous (63%, P<0.05. CONCLUSIONS: Tennis at prepubertal age is associated with marked hypertrophy of the dominant arm, leading to a marked level of asymmetry (+13%, much greater than observed in non-active controls (+3%. Therefore, tennis particpation at prepubertal age is associated with increased muscle volumes in dominant compared to the non-dominant arm, likely due to selectively hypertrophy of the loaded muscles.

  1. Clinical profile and pattern of adenoid hypertrophy among children ...

    African Journals Online (AJOL)

    Introduction: The objective of this study was to determine the pattern, clinical profile and surgical intervention in children presenting with adenoids hypertrophy in a private hospital. Methods: The study was conducted at the general pediatric clinic of a private hospital in Enugu, south east Nigeria in collaboration with a ...

  2. Patient with Benign Prostatic Hypertrophy and Two Giant Stones in ...

    African Journals Online (AJOL)

    Giant urinary bladder stones are very rare; very few cases have been reported in English literature and only one case from Africa. Multiple giant bladder stones are extremely rare; no single case report has been found documenting this occasion. This report presents a patient of benign prostatic hypertrophy with two giant ...

  3. G protein-coupled receptor kinase 2 promotes cardiac hypertrophy

    Science.gov (United States)

    Tscheschner, Henrike; Gao, Erhe; Schumacher, Sarah M.; Yuan, Ancai; Backs, Johannes; Most, Patrick; Wieland, Thomas; Koch, Walter J.; Katus, Hugo A.; Raake, Philip W.

    2017-01-01

    The increase in protein activity and upregulation of G-protein coupled receptor kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure. Inhibition of GRK2 improved cardiac function and survival and diminished cardiac remodeling in various animal heart failure models. The aim of the present study was to investigate the effects of GRK2 on cardiac hypertrophy and dissect potential molecular mechanisms. In mice we observed increased GRK2 mRNA and protein levels following transverse aortic constriction (TAC). Conditional GRK2 knockout mice showed attenuated hypertrophic response with preserved ventricular geometry 6 weeks after TAC operation compared to wild-type animals. In isolated neonatal rat ventricular cardiac myocytes stimulation with angiotensin II and phenylephrine enhanced GRK2 expression leading to enhanced signaling via protein kinase B (PKB or Akt), consecutively inhibiting glycogen synthase kinase 3 beta (GSK3β), such promoting nuclear accumulation and activation of nuclear factor of activated T-cells (NFAT). Cardiac myocyte hypertrophy induced by in vitro GRK2 overexpression increased the cytosolic interaction of GRK2 and phosphoinositide 3-kinase γ (PI3Kγ). Moreover, inhibition of PI3Kγ as well as GRK2 knock down prevented Akt activation resulting in halted NFAT activity and reduced cardiac myocyte hypertrophy. Our data show that enhanced GRK2 expression triggers cardiac hypertrophy by GRK2-PI3Kγ mediated Akt phosphorylation and subsequent inactivation of GSK3β, resulting in enhanced NFAT activity. PMID:28759639

  4. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy ...

    African Journals Online (AJOL)

    Western blot was used to analyze the expression of some glycolytic proteins, including Glut-1, hexokinase (HXK-2), and enolase, while apoptosis of H9C2 was determined by flow cytometry. Results: PE caused hypertrophy in H9C2, which was ameliorated by HIF-1α. Compared to normal, under prolonged high glucose, the ...

  5. Massive Assymetrical Virginal Breast Hypertrophy: A Case Report ...

    African Journals Online (AJOL)

    Virginal breast hypertrophy (VHB) is a rare , distinct disorder of unknown etiology with the rapid onset of macromastia at the onset of puberty.We reported a 12 year old, peripubertal girl presented to us with abnormal assymetrical growth of her breasts in 10 months. Due to the enormous breast volume, which caused her ...

  6. Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy.

    Science.gov (United States)

    Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K

    2002-11-15

    Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.

  7. Myocardial hypertrophy overrides the angiogenic response to hypoxia.

    Directory of Open Access Journals (Sweden)

    Yeong-Hoon Choi

    Full Text Available Cyanosis and myocardial hypertrophy frequently occur in combination. Hypoxia or cyanosis can be potent inducers of angiogenesis, regulating the expression of hypoxia-inducible factors (HIF, vascular endothelial growth factors (VEGF, and VEGF receptors (VEGFR-1 and 2; in contrast, pressure overload hypertrophy is often associated with impaired pro-angiogenic signaling and decreased myocardial capillary density. We hypothesized that the physiological pro-angiogenic response to cyanosis in the hypertrophied myocardium is blunted through differential HIF and VEGF-associated signaling.Newborn rabbits underwent aortic banding and, together with sham-operated littermates, were transferred into a hypoxic chamber (FiO(2 = 0.12 at 3 weeks of age. Control banded or sham-operated rabbits were housed in normoxia. Systemic cyanosis was confirmed (hematocrit, arterial oxygen saturation, and serum erythropoietin. Myocardial tissue was assayed for low oxygen concentrations using a pimonidazole adduct. At 4 weeks of age, HIF-1alpha and HIF-2alpha protein levels, HIF-1alpha DNA-binding activity, and expression of VEGFR-1, VEGFR-2, and VEGF were determined in hypoxic and normoxic rabbits. At 6 weeks of age, left-ventricular capillary density was assessed by immunohistochemistry. Under normoxia, capillary density was decreased in the banded rabbits compared to non-banded littermates. As expected, non-hypertrophied hearts responded to hypoxia with increased capillary density; however, banded hypoxic rabbits demonstrated no increase in angiogenesis. This blunted pro-angiogenic response to hypoxia in the hypertrophied myocardium was associated with lower HIF-2alpha and VEGFR-2 levels and increased HIF-1alpha activity and VEGFR-1 expression. In contrast, non-hypertrophied hearts responded to hypoxia with increased HIF-2alpha and VEGFR-2 expression with lower VEGFR-1 expression.The participation of HIF-2alpha and VEGFR-2 appear to be required for hypoxia

  8. Physical and emotional disturbances in children with adenotonsillar hypertrophy.

    Science.gov (United States)

    Kurnatowski, P; Putyński, L; Łapienis, M; Kowalska, B

    2008-09-01

    Enlarged tonsils and adenoids (part of Waldeyer's ring) are responsible for obstructive sleep disordered breathing. Obstructive sleep disordered breathing episodes lead to hypoxaemia, hypercapnia and a state of arousal, all of which affect normal development of the nervous system. In this study, two hypotheses were tested: (1) obstructive sleep disordered breathing is caused by adenotonsillar hypertrophy and is associated with hypoxia and brain dysfunction; and (2) children with obstructive sleep disordered breathing more commonly display emotional lability, depressive behaviour and anxiety. A total of 225 children were examined. The study group consisted of 121 children with adenotonsillar hypertrophy (87 aged six to nine years and 34 aged 10 to 13 years) and with obstructive sleep apnoeas and hypopnoeas confirmed by polysomnography. Patients were compared with 104 children with no obstructive sleep disordered breathing and no adenotonsillar hypertrophy (74 aged six to nine years and 30 aged 10 to 13 years). The following tests were used to measure the children's emotional disorders: the children's depression inventory; the state-trait anxiety inventory for children; and the emotional instability scale. The average values and standard deviations were calculated for all results. Student's t-test was used to compare differences in all groups of children. The minimum level of p Children with adenotonsillar hypertrophy are more likely to experience poor brain development and sleep problems. They also have emotional disturbances. In the sick and healthy children aged six to nine years, mean results for the emotional instability scale were statistically significantly different in the two groups, being higher in children with adenotonsillar hypertrophy than in healthy children. Mean values for the children's depression inventory test were higher in children with adenotonsillar hypertrophy, but the differences were not statistically significant. In the state-trait anxiety

  9. GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet

    DEFF Research Database (Denmark)

    McClean, Paula L; Irwin, Nigel; Cassidy, Roslyn S

    2007-01-01

    tissue mass, adipocyte hypertrophy, and deposition of triglyceride in liver and muscle were significantly decreased. These changes were accompanied by significant improvement of insulin sensitivity, meal tolerance, and normalization of glucose tolerance in (Pro(3))GIP-treated high-fat-fed mice. (Pro(3...

  10. Cinnamaldehyde attenuates pressure overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Yang, Liu; Wu, Qing-Qing; Liu, Yuan; Hu, Zhe-Fu; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-01-01

    Cinnamaldehyde is a major bioactive compound isolated from the leaves of Cinnamomum osmophloeum. Studies have demonstrated that cinnamaldehyde has anti-bacterial activity, anti-tumorigenic effect, immunomodulatory effect, anti-fungal activity, anti-oxidative effect, anti-inflammatory and anti-diabetic effect. It has been proven that Cinnamaldehyde improves ischemia/reperfusion injury of pre-treatment. However, little is known about the effect of cinnamaldehyde on cardiac hypertrophy. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cinnamaldehyde premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at week 7 after starting cinnamaldehyde (8 weeks after surgery). The extent of cardiac hypertrophy was evaluated by pathological and molecular analyses of heart samples. Meanwhile, the effect of cinnamaldehyde on myocardial hypertrophy, fibrosis and dysfunction induced by AB was investigated, as was assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Our data demonstrated that echocardiography and catheter-based measurements of hemodynamic parameters at week 7 revealed the amelioration of systolic and diastolic abnormalities by cinnamaldehyde intervention. Cardiac fibrosis in AB mice was also decreased by cinnamaldehyde. Moreover, the beneficial effect of cinnamaldehyde was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of extracellular signal-regulated kinase (ERK) signaling pathway, which was blocked by cinnamaldehyde. Cinnamaldehyde may be able to retard the progression of cardiac hypertrophy and fibrosis, probably via blocking ERK signaling pathway.

  11. Weighing in on Dietary Fats

    Science.gov (United States)

    ... lower-fat ingredients. “Low-fat and fat-free yogurt and milk still contain the important proteins and minerals found in the full-fat versions, but you’re getting less saturated fat and cholesterol,” McDowell says. “In some recipes, you can use ...

  12. Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy.

    Science.gov (United States)

    Liu, Yonggang; Chien, Wei-Ming; Medvedev, Ivan O; Weldy, Chad S; Luchtel, Daniel L; Rosenfeld, Michael E; Chin, Michael T

    2013-10-05

    Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse by exposing mice to DE combined with either of two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure overload induced by transverse aortic banding. Wild type male C57BL/6 J mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump implanted subcutaneously for 1 month, or underwent transverse aortic banding (27 gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6 months for observing chronic reactions). Vehicle (saline) infusion or sham surgery was used as a control. Shortly after surgery, mice were transferred to our exposure facility and randomly assigned to either diesel exhaust (300 or 400 μg/m(3)) or filtered air exposures. After reaching the end of designated time points, echocardiography was performed to measure heart structure and function. Gravimetric analysis was used to measure the ventricular weight to body weight ratio. We also measured heart rate by telemetry using implanted ambulatory ECG monitors. Both angiotensin II and transverse aortic banding promoted cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic banding for six months also promoted heart failure in addition to cardiac hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy or heart failure when compared to filtered air controls. Prolonged DE exposure also led to a decrease in average heart rate. Up to 6-months of DE exposure had no effect on cardiac hypertrophy and heart function induced by

  13. Impact of house fly salivary gland hypertrophy virus (MdSGHV) on a heterologous host, Stomoxys calcitrans.

    Science.gov (United States)

    Geden, C; Garcia-Maruniak, A; Lietze, V U; Maruniak, J; Boucias, D G

    2011-11-01

    The effect of Musca domestica salivary gland hypertrophy virus (MdSGHV) on selected fitness parameters of stable flies, Stomoxys calcitrans (L.), was examined in the laboratory. Virus-injected stable flies of both genders suffered substantially higher mortality than control flies. By day 9, female mortality was 59.3 +/- 10.1% in the virus group compared with 23.7 +/- 3.7% in the controls; mortality in virus-injected males was 78.1 +/- 3.1% compared with 33.3 +/- 9.3% for controls. Fecundity of control flies on days 6-9 was 49-54 eggs deposited per live female per day (total, 8,996 eggs deposited), whereas virus-injected flies produced four to five eggs per female on days 6-7 and less then one egg per female per day thereafter (total, 251 eggs). Fecal spot deposition by virus-injected flies was comparable to controls initially but decreased to approximately 50% of control levels by day 4 after injection; infected flies produced only 26% as many fecal spots as healthy flies on days 6 and 7. None of the virus-injected stable flies developed symptoms of salivary gland hypertrophy. Quantitative real-time polymerase chain reaction demonstrated virus replication in injected stable flies, with increasing titers of virus genome copies from one to four days after injection. MdSGHV in stable flies displayed tissue tropism similar to that observed in house fly hosts, with higher viral copy numbers in fat body and salivary glands compared with ovaries. Virus titers were approximately 2 orders of magnitude higher in house fly than in stable fly hosts, and this difference was probably due to the absence of salivary gland hypertrophy in the latter species.

  14. Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

    Science.gov (United States)

    Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

    2013-01-01

    We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

    Science.gov (United States)

    Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

    2014-01-01

    A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

  16. Differential and conditional activation of PKC-isoforms dictates cardiac adaptation during physiological to pathological hypertrophy.

    Science.gov (United States)

    Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

    2014-01-01

    A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation.

  17. Dietary fat and carcinogenesis

    NARCIS (Netherlands)

    Woutersen, R.A.; Appel, M.J.; Garderen-Hoetmer, A. van; Wijnands, M.V.W.

    1999-01-01

    Epidemiologic investigations have suggested a relationship between dietary fat intake and various types of cancer incidences. Furthermore, epidemiologic studies as well as studies with animal models have demonstrated that not only the amount but also the type of fat consumed is important. At

  18. Trans-polar-fat

    DEFF Research Database (Denmark)

    Counil, Emilie; Dewailly, Eric; Bjerregaard, Peter

    2008-01-01

    As part of the rapid socio-cultural transition observed in Arctic populations, the Inuit diet is changing. We present original data derived from the baseline Inuit Health in Transition cohort study regarding biological levels of n-3 fatty acids and trans-fatty acids (TFA), lipids with opposite he...... of 2 g/100 g fat on industrially produced trans-fats in 2003....

  19. Dietary fats and cancer

    NARCIS (Netherlands)

    Zock, P.L.

    2001-01-01

    The present review addresses the evidence for a possible link between dietary fat and cancer. International comparisons suggest that a high-fat diet may increase cancer risk, and this hypothesis is supported by animal experiments. However, epidemiological studies within populations show little or

  20. Learning about Fats

    Science.gov (United States)

    ... and other animal products, such as butter and cheese. Saturated fats are also in palm and coconut oils, which are often used in baked goods you buy at the store. Eating too much saturated fat can raise blood cholesterol levels and increase the chance of getting heart ...

  1. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strøm, Claes C; Kruhøffer, Mogens; Knudsen, Steen

    2004-01-01

    Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic...... gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved...... genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may...

  2. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strom, C.C.; Kruhoffer, M.; Knudsen, Steen

    2004-01-01

    gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved...... in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61...... genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may...

  3. Left Ventricular Hypertrophy: Major Risk Factor in Patients with Hypertension: Update and Practical Clinical Applications

    Directory of Open Access Journals (Sweden)

    Richard E. Katholi

    2011-01-01

    Full Text Available Left ventricular hypertrophy is a maladaptive response to chronic pressure overload and an important risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension. Since not all patients with hypertension develop left ventricular hypertrophy, there are clinical findings that should be kept in mind that may alert the physician to the presence of left ventricular hypertrophy so a more definitive evaluation can be performed using an echocardiogram or cardiovascular magnetic resonance. Controlling arterial pressure, sodium restriction, and weight loss independently facilitate the regression of left ventricular hypertrophy. Choice of antihypertensive agents may be important when treating a patient with hypertensive left ventricular hypertrophy. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers followed by calcium channel antagonists most rapidly facilitate the regression of left ventricular hypertrophy. With the regression of left ventricular hypertrophy, diastolic function and coronary flow reserve usually improve, and cardiovascular risk decreases.

  4. Fat and bone interactions.

    Science.gov (United States)

    Bermeo, Sandra; Gunaratnam, Krishanthi; Duque, Gustavo

    2014-06-01

    Fat and bone have a complicated relationship. Although obesity has been associated with low fracture risk, there is increasing evidence that some of the factors that are released by peripheral fat into the circulation may also have a deleterious effect on bone mass, thus, predisposing to fractures. More importantly, the local interaction between fat and bone within the bone marrow seems to play a significant role in the pathogenesis of age-related bone loss and osteoporosis. This "local interaction" occurs inside the bone marrow and is associated with the autocrine and paracrine release of fatty acids and adipokines, which affect the cells in their vicinity including the osteoblasts, reducing their function and survival. In this review, we explore the particularities of the fat and bone cell interactions within the bone marrow, their significance in the pathogenesis of osteoporosis, and the potential therapeutic applications that regulating marrow fat may have in the near future as a novel pharmacologic treatment for osteoporosis.

  5. Differential fat harvesting

    Directory of Open Access Journals (Sweden)

    Sebastian Torres Farr

    2014-12-01

    Full Text Available Aim: Volume replacement with fillers is regularly performed with the use of diverse volumetric materials to correct different structures around the face, depending on the volume enhancement required and the thickness of the soft tissue envelope. Differential fat harvesting and posterior grafting is performed to place the correct fat parcel size for each target area, expanding the potential applications of fat. Methods: Sixty patients consecutively recruited on a first come basis undergone a facial fat grafting procedure, in private practice setting between March 2012 and October 2013. Fat grafting quantity and quality was predicted for each case. Differential harvesting was performed, with 2 fat parcels size. Processing was performed through washing. Fat infiltration was carried out through small cannulas or needles depending on the treated area. Outcomes were analysed both by the physicians and the patients at 7 days, 1 month, 3 months and 6 months through a perceived satisfaction questionnaire. Parameters considered were downtime or discomfort, skin benefits, volume restoration, reabsorption rate estimated and overall improvement. Results: Full facial differential fat grafting procedure lasted an average of 1.5-2.5 h. Average downtime was 3-4 days. Follow-up was performed to a minimum of 6 months. Both patient and physician overall satisfaction rates were mostly excellent. Adverse events like lumps or irregularities were not encountered. Conclusion: Differential fat harvesting and posterior grafting is a valid alternative, to expand the repertoire of fat use, allow a more homogeneous effect, reduce the potential complications, speed up the process, improve graft survival, and to enhance overall aesthetic outcome.

  6. Tuberous breast correction by fat grafting.

    Science.gov (United States)

    Delay, Emmanuel; Sinna, Raphaël; Ho Quoc, Christophe

    2013-05-01

    Tuberous breast is a rare malformation that has negative physical and psychological impacts during puberty. A range of surgical techniques has been used to correct breast shape and volume in this context, including a combination of skin plasty and mammary gland remodeling, as well as prostheses and locoregional flaps. The authors have used fat grafting as a complementary technique to correct tuberous breasts since 1998. The authors discuss application of their lipomodeling technique for correction of tuberous breast deformity. The charts of tuberous breast patients treated consecutively over an 11-year period (n = 31) solely with fat grafting (ie, without using an implant) were retrospectively reviewed. Each breast deformation was graded according to the Grolleau classification. The number of sessions and the mean transfer of fat volume by lipomodeling session were recorded. Patient and surgeon satisfaction were evaluated. Of the 31 patients in this series, 18 had bilateral formations and 13 had unilateral malformations. The mean patient age was 23 years, and the mean body mass index was 21.9. A single session (mean transfer volume, 158 mL; range, 90-253 mL) was required in 14 (45%) cases. A second session (mean transfer volume, 226 mL; range, 100-316 mL) was necessary in the remaining 55% of cases. Mean follow-up period after the last fat transfer session was 6.5 years (range, 1.5-11 years). Patients were very satisfied in 94% of cases (n = 29) and satisfied in 6% (n = 2). The surgical team rated 94% of cases as being successful or very successful. No complications were observed. One patient developed hypertrophy of the treated breast following weight gain and thus required breast reduction. Imaging performed preoperatively and 1 year postoperatively did not reveal any anomalies other than oil cysts. Fat grafting is a reliable technique that produces excellent results and high levels of patient satisfaction for the treatment of tuberous breast. The aesthetic

  7. Dietary obacunone supplementation stimulates muscle hypertrophy, and suppresses hyperglycemia and obesity through the TGR5 and PPARγ pathway

    Energy Technology Data Exchange (ETDEWEB)

    Horiba, Taro, E-mail: thoriba@mail.kikkoman.co.jp [Research and Development Division, Kikkoman Corporation, Chiba (Japan); Katsukawa, Masahiro [Research and Development Division, Kikkoman Corporation, Chiba (Japan); Mita, Moeko; Sato, Ryuichiro [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo (Japan)

    2015-08-07

    Obacunone is a limonoid that is predominantly found in Citrus. Although various biological activities of limonoids have been reported, little is known about the beneficial effects of obacunone on metabolic disorders. In the present study, we examined the effects of dietary obacunone supplementation on obese KKAy mice, to clarify the function of obacunone in metabolic regulation. Mice were pair-fed a normal diet either alone or supplemented with 0.1% w/w obacunone for 28 days. Compared with the control, obacunone-fed mice had lower glycosylated hemoglobin, blood glucose, and white adipose tissue weight, although there was no significant difference in body weight. Obacunone treatment also significantly increased the weight of the gastrocnemius and quadriceps muscles. Reporter gene assays revealed that obacunone stimulated the transcriptional activity of the bile acids-specific G protein-coupled receptor, TGR5, in a dose-dependent manner. In addition, obacunone inhibited adipocyte differentiation in 3T3-L1 cells and antagonized ligand-stimulated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. These results suggest that obacunone stimulates muscle hypertrophy and prevents obesity and hyperglycemia, and that these beneficial effects are likely to be mediated through the activation of TGR5 and inhibition of PPARγ transcriptional activity. - Highlights: • Citrus limonoid obacunone prevents hyperglycemia in obese, diabetic KKAy mice. • Obacunone reduces fat content and stimulates muscle hypertrophy in KKAy mice. • Obacunone stimulates TGR5 transcriptional activities. • Obacunone antagonizes PPARγ and inhibits lipid accumulation in adipocytes.

  8. Abdominal wall fat pad biopsy

    Science.gov (United States)

    Amyloidosis - abdominal wall fat pad biopsy; Abdominal wall biopsy; Biopsy - abdominal wall fat pad ... method of taking an abdominal wall fat pad biopsy . The health care provider cleans the skin on ...

  9. Face the Fats Quiz 2

    Science.gov (United States)

    Face the Fats Quiz II Do you know your fats by heart? Ready to make informed choices about the foods you ... to fried chicken, test your knowledge about the fats in some familiar foods. Welcome to Face the ...

  10. Prevention of anemia alleviates heart hypertrophy in copper deficient rats

    Energy Technology Data Exchange (ETDEWEB)

    Lure, M.D.; Fields, M.; Lewis, C.G. (Dept. of Agriculture, Beltsville, MD (United States) Univ. of Maryland, College Park (United States) Georgetown Univ., Washington, DC (United States))

    1991-03-11

    The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severe signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.

  11. Genome-wide expression patterns in physiological cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Ouzounis Christos A

    2010-10-01

    Full Text Available Abstract Background Genome-wide expression patterns in physiological cardiac hypertrophy. Co-expression patterns in physiological cardiac hypertrophy Results In this study, the first large-scale analysis of publicly available genome-wide expression data of several in vivo murine models of physiological LVH was carried out using network analysis. On evaluating 3 million gene co-expression patterns across 141 relevant microarray experiments, it was found that physiological adaptation is an evolutionarily conserved processes involving preservation of the function of cytochrome c oxidase, induction of autophagy compatible with cell survival, and coordinated regulation of angiogenesis. Conclusion This analysis not only identifies known biological pathways involved in physiological LVH, but also offers novel insights into the molecular basis of this phenotype by identifying key networks of co-expressed genes, as well as their topological and functional properties, using relevant high-quality microarray experiments and network inference.

  12. Region specific patella tendon hypertrophy in humans following resistance training

    DEFF Research Database (Denmark)

    Kongsgaard, M.; Reitelseder, S; Pedersen, T.G.

    2007-01-01

    AIM: To examine if cross-sectional area (CSA) differs along the length of the human patellar tendon (PT), and if there is PT hypertrophy in response to resistance training. METHODS: Twelve healthy young men underwent baseline and post-training assessments. Maximal isometric knee extension strength......, subjects performed 12 weeks of heavy resistance knee extension training with one leg (Heavy-leg), and light resistance knee extension training with the other leg (Light-leg). RESULTS: The MVC increased for heavy-leg (15 +/- 4%, P .... CONCLUSIONS: To our knowledge, this study is the first to report tendon hypertrophy following resistance training. Further, the data show that the human PT CSA varies along the length of the tendon....

  13. Repeated blood flow restriction induces muscle fiber hypertrophy.

    Science.gov (United States)

    Sudo, Mizuki; Ando, Soichi; Kano, Yutaka

    2017-02-01

    We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. CSA was greater in the BFR+ECC group than in the CONT (P hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. © 2016 Wiley Periodicals, Inc.

  14. Malondialdehyde in benign prostate hypertrophy: a useful marker?

    Directory of Open Access Journals (Sweden)

    Rosaria Alba Merendino

    2003-01-01

    Full Text Available Benign prostate hypertrophy (BPH is the most common benign tumor in men due to obstruction of the urethra and, finally, uremia. Malondialdehyde (MDA is a product derived from peroxidation of polyunsaturated fatty acids and related esters. Evaluation of MDA in serum represents a non-invasive biomarker of oxidative stress. Prostate-specific antigen (PSA is a sensitive marker for prostatic hypertrophy and cancer. We analyzed MDA serum levels to evaluate the oxidative stress in BPH. To this end, 22 BPH patients and 22 healthy donors were enrolled. Data show an increase of MDA level in BPH patients and a positive correlation between PSA and MDA levels. In conclusion, we describe a previously unknown relationship between PSA and MDA as an index of inflammation and oxidative stress in BPH.

  15. Role of microtubules in the contractile dysfunction of hypertrophied myocardium

    Science.gov (United States)

    Zile, M. R.; Koide, M.; Sato, H.; Ishiguro, Y.; Conrad, C. H.; Buckley, J. M.; Morgan, J. P.; Cooper, G. 4th

    1999-01-01

    OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

  16. Sex differences in physiological and pathological myocardial hypertrophy in mice

    OpenAIRE

    Cantow, Kathleen

    2011-01-01

    Premenopausal women appear to have a lower incidence of myocardial infarction (MI) and reduced mortality compared with age-matched men. Clinical studies suggest a protective effect of the female sex hormone Estradiol during the development of pathological hypertrophy. Furthermore it is known that exercise positively influences the outcome of cardiovascular disease, which is more pronounced in females than males. To better understand the shown sex differences and underlying mechanisms, this...

  17. Glomerular alterations in pulmonary hypertension and right ventricular hypertrophy

    OpenAIRE

    Cadillo Alfaro, Mario; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The purpose of this work was to study the renal abnormalities in patients with pulmonary hypertension, irrespective of their origin (unless there is evidence of a mitral lesion) and in those not taking full evidence of pulmonary hypertension, right ventricular hypertrophy was found present. Little has been written on this topic, even the poorest are conclusions, not knowing until now the pathogenic factors of renal impairment; least of their pathophysiological significance. El objeto del p...

  18. Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide

    Science.gov (United States)

    2017-07-01

    ultimate human subject testing. 2. KEYWORDS: Osteoarthritis Parathyroid hormone-related protein PTH receptor -catenin Cell signaling...To further verify our results, we will repeat the experiments with mouse bone marrow-derived mesenchymal stem cell differentiation to chondrocytes...AWARD NUMBER: W81XWH-16-1-0325 TITLE: Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide PRINCIPAL INVESTIGATOR: Bin

  19. Gingival hypertrophy in a child: Expect the unexpected

    OpenAIRE

    Ravikumar, Rekha; Manohar, Rakesh; Latha, Sneha Magatha; Scott, Julius Xavier

    2016-01-01

    Acute leukemia is the most common malignant disorder of childhood. Acute leukemia is characterized by marrow failure due to the replacement of marrow elements by leukemic blasts. Gingival hypertrophy (GH) due to acute myeloid leukemia (AML) in a child is extremely rare. Here, we report a case of AML (subtype M5 of FAB classification) in a 3-year-old male child wherein the disease primarily presented as GH.

  20. The Natural History of Soft Tissue Hypertrophy, Bony Hypertrophy, and Nodule Formation in Patients With Untreated Head and Neck Capillary Malformations.

    Science.gov (United States)

    Lee, Jeong Woo; Chung, Ho Yun; Cerrati, Eric W; O, Teresa M; Waner, Milton

    2015-11-01

    A percentage of patients with capillary malformation (CM) develop soft tissue hypertrophy, bony hypertrophy, and/or nodule formation. To determine the incidence, age of onset, anatomic distribution of soft tissue/bony hypertrophy, and nodule formation in patients with untreated CM. A retrospective medical records review of head and neck CM patients presenting to a tertiary referral center over a 7-year period (2004-2011) was performed. Of the 160 patients with CM, 96 demonstrated progression of disease to include either soft tissue/bony hypertrophy or nodule formation. Of these, 87 patients had not received previous treatment and met the inclusion criteria for analysis. On average, soft tissue hypertrophy began at 9 years of age. The V2/maxillary segment was most commonly involved with upper lip hypertrophy being the most prominent. Fourteen percent of the patients also presented with bony hypertrophy, which began at an average age of 15 years. Nodules were present in 38/87 (44%) of patients with an average age of onset of 22 years. This study demonstrates the nature progression of CM and quantifies the clinical characteristics of hypertrophy and nodule formation with untreated head and neck CM. Early and continuous treatment is recommended in hopes of preventing CM progression.

  1. Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    An, Xiangbo; Wang, Jingjing; Li, Hao; Lu, Zhizhen; Bai, Yan; Xiao, Han; Zhang, Youyi; Song, Yao

    2016-01-01

    Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS), radial strain rate (RSR) and longitudinal strain (LS), showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E', an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS), E/A and E'/A' at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy.

  2. Management of hypertrophied dural lesions: Is surgery a better option?

    Science.gov (United States)

    Ogiwara, Toshihiro; Nagm, Alhusain; Hanaoka, Yoshiki; Nishikawa, Akihiro; Goto, Tetsuya; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro

    2017-10-15

    It is often difficult to definitively diagnose dural lesions with hypertrophy as they exhibit nonspecific imaging findings and clinical symptoms. Most cases require histopathological evaluation with surgical intervention (such as biopsy). However, complications related to surgical interventions remain as matter of concern. Herein, we analyzed and verified the significance of surgery in 39 patients with hypertrophic dural lesions who were histopathologically diagnosed with surgical interventions. Specimens of dural lesions were obtained successfully, and it was possible to make a definitive diagnosis for each case based on histopathological findings. All patients tolerate the procedures well, and there were no evidences of surgery-related complications during surgical approach to the dura mater. Preoperative and pathological diagnoses varied in eight cases. Our results indicate that histopathological evaluation is important for distinguishing diseases showing dural hypertrophy even if surgical invasiveness is concerned. Neurosurgeons should not hesitate to perform surgery for management of dural lesions with hypertrophy in order to achieve accurate diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Testosterone levels in benign prostatic hypertrophy and prostate cancer.

    Science.gov (United States)

    Mearini, Luigi; Costantini, Elisabetta; Zucchi, Alessandro; Mearini, Ettore; Bini, Vittorio; Cottini, Emanuele; Porena, Massimo

    2008-01-01

    Although hormones play fundamental roles in prostate growth, their clinical significance is not completely clear. In the present study we assessed whether serum hormone levels are markers of prostate disease. In 128 patients with benign prostatic hypertrophy or prostate cancer, testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels were correlated with disease. In patients with prostate cancer, the hormone levels were also correlated with prognostic factors. Predictive values were assessed for prostate-specific antigen and testosterone levels only, using multiple logistic regression analysis and receiver operating characteristic curves. The testosterone concentrations were significantly lower in patients with prostate cancer than in those with benign prostatic hypertrophy and were also significantly lower in patients with advanced-stage disease than in patients with organ-confined disease. Testosterone appears to be an independent predictor of disease and enhances the predictive accuracy for benign prostatic hypertrophy and prostate cancer. This study supports experimental findings that prostate cancer is frequently associated with low testosterone concentrations. In the diagnostic workup for prostate cancer, associating prostate-specific antigen and testosterone levels may improve the predictive accuracy of prostate disease tests.

  4. The frequency of benign prostate hypertrophy in Calabar.

    Science.gov (United States)

    Umezurike, B I; Ekanem, T B; Eluwa, M A; Etta, K K; Udo-Affah, G A; Aligwekwe, A U

    2006-09-01

    The present study was to find out through histopathological records the most frequently occurring disease of the prostate from suspected prostate diseases in Calabar, Cross River State, Nigeria. A total number of 324 cases of prostatic biopsies and autopsy materials recorded in the histopathology laboratory of the University of Calabar Teaching Hospital (UCTH), Calabar between 1986 and 1995 were used for this study. Benign prostatic hypertrophy was observed as the major pathology among all the diseases of the prostate gland recorded in UCTH in Calabar having accounted for 76.3% (261 out of 342) while prostatic carcinoma accounted for 19% (65 out of 324), rest 4.7% (16 out of 342) were inflammatory lesions. The result indicated that benign prostatic hypertrophy occurs in men from 40 years and above. The frequency increased with age, reaching a maximum of 34.5% (90 out of 261) in the age group (70-79) years old. The people in Cross River State should be informed of the high frequency of benign prostatic hypertrophy and should be advised to seek health care promptly in suspected prostate related illness.

  5. Electrocardiographic patterns of patients with echocardiographically determined biventricular hypertrophy.

    Science.gov (United States)

    Jain, A; Chandna, H; Silber, E N; Clark, W A; Denes, P

    1999-07-01

    The numerous criteria proposed for the electrocardiographic (ECG) diagnosis of biventricular hypertrophy (BVH) suffer from inadequate correlative data. We used two-dimensional (2D) echocardiography to identify BVH and analyzed the ECG patterns in these patients. The study group had 69 such patients with BVH and the control group had 22 patients with isolated left ventricular hypertrophy (LVH) demonstrated by 2D echocardiography. The electrocardiograms were analyzed for the presence of established criteria used in the diagnosis of LVH and right ventricular hypertrophy (RVH). Of the 69 patients in the study group, 17 (25%) had ECG findings of BVH, 25 (36%) had LVH, and 14 (20%) had RVH. An S wave in V5/V6 of >7 mm was most the frequent finding in the 17 patients with BVH on the electrocardiogram. The sensitivity of ECG criteria for BVH was 24.6%, specificity was 86.4%, and positive predictive value was 85%. This study reemphasizes the difficulty of ECG diagnosis of BVH. The electrocardiogram has a low sensitivity but satisfactory specificity and positive predictive accuracy for BVH.

  6. Effect of prophylactic digitalization on the development of myocardial hypertrophy.

    Science.gov (United States)

    Cutilletta, A F; Rudnik, M; Arcilla, R A; Straube, R

    1977-11-01

    The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

  7. Estrogens mediate cardiac hypertrophy in a stimulus-dependent manner.

    Science.gov (United States)

    Haines, Christopher D; Harvey, Pamela A; Leinwand, Leslie A

    2012-09-01

    The incidence of cardiac hypertrophy, an established risk factor for heart failure, is generally lower in women compared with men, but this advantage is lost after menopause. Although it is widely believed that estrogens are cardioprotective, there are contradictory reports, including increased cardiac events in postmenopausal women receiving estrogens and enhanced cardiac protection from ischemic injury in female mice without estrogens. We exposed aromatase knockout (ArKO) mice, which produce no estrogens, to both pathologic and physiologic stimuli. This model allows an investigation into the effects of a complete, chronic lack of estrogens in male and female hearts. At baseline, female ArKO mice had normal-sized hearts but decreased cardiac function and paradoxically increased phosphorylation of many progrowth kinases. When challenged with the pathological stimulus, isoproterenol, ArKO females developed 2-fold more hypertrophy than wild-type females. In contrast, exercise-induced physiological hypertrophy was unaffected by the absence of estrogens in either sex, although running performance was blunted in ArKO females. Thus, loss of estrogen signaling in females, but not males, impairs cardiac function and sensitizes the heart to pathological insults through up-regulation of multiple hypertrophic pathways. These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention.

  8. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  9. Astrocyte Hypertrophy Contributes to Aberrant Neurogenesis after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Clark Robinson

    2016-01-01

    Full Text Available Traumatic brain injury (TBI is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI.

  10. High fat diet aggravates atrial and ventricular remodeling of hypertensive heart disease in aging rats.

    Science.gov (United States)

    Shiou, Yi-Lin; Huang, I-Chieh; Lin, Hsin-Ting; Lee, Hsiang-Chun

    2017-09-06

    Left ventricular hypertrophy is a major cause of heart failure in aging population. This study is to determine whether an excess dietary fat is lipotoxic or lipoprotein to the hypertrophic aging heart. At 44-week-old, a normal chow (12% fat) was replaced a high-fat diet (HFD; 45% fat) for randomly selective spontaneously hypertensive rats (SHR + HFD, n = 6) and Wistar-Kyoto rats (WKY + HFD, n = 6, normotensive control). Others (SHR, n = 11; WKY, n = 10) were continuously fed with normal diets. After 27 weeks, electrocardiogram, echocardiography, and femoral arterial catheterization were performed before rats being sacrificed for molecular biology analyses. HFD aggravated cardiac atrial, ventricular dilation and hypertrophy in SHR (LV mass: SHR + HFD 2026.0 ± 424.9 vs SHR 1449 ± 461.1 mg, unpaired t test P heart disease in aging rats was aggravated by HFD with worse atrial, ventricular remodeling and associated with left ventricular systolic function impairment. Copyright © 2017. Published by Elsevier B.V.

  11. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

    Full Text Available Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulates health and lifespan.

  12. Fecal Fat: The Test

    Science.gov (United States)

    ... weeks to delivery) Prostate Cancer Protein in Urine (Proteinuria) Reactive Arthritis Rheumatoid Arthritis Sarcoidosis Scleroderma Sepsis Septic ... healthcare practitioner's instructions; this may include consuming 50-150 grams of fat a day in your diet ...

  13. Fecal Fat: The Test

    Science.gov (United States)

    ... Pregnancy hCG Tumor Marker HDL Cholesterol Heavy Metals Helicobacter pylori Testing Hematocrit Hemoglobin Hemoglobin A1c Hemoglobinopathy Evaluation ... 150 grams of fat a day in your diet for 2-3 days prior to and during ...

  14. Drink Water, Fight Fat?

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_165714.html Drink Water, Fight Fat? When you have it in place ... HealthDay News) -- If you choose a glass of water instead of a beer or a sugar-sweetened ...

  15. What Are Solid Fats?

    Science.gov (United States)

    ... TIPS: Vary Your Veggies Beans and Peas Are Unique Foods Food Gallery Take the Vegetable Quiz Grains ... Foods and Beverages Saturated, Unsaturated, and Trans Fats Sodium Added Sugars Others Everything You Eat and Drink ...

  16. Alternative fat sources to animal fat for pigs

    DEFF Research Database (Denmark)

    Lauridsen, Charlotte; Christensen, Thomas Bruun; Halekoh, Ulrich

    2007-01-01

    % of either animal fat, palm oil mix, palm oil, vegetable oil mix, coconut oil, or rapeseed oil were tested in weaned and growing pigs. It was concluded that several vegetable fat sources (palm oil mix, palm oil, coconut oil, rapeseed oil) could be used as alternatives to animal fat in pig feed, whereas fat......The use of fats and oils in diets for pigs is of great importance due to their high energy value. As a consequence of the BSE-crisis in the European Union, the amount of animal fat available for animal feeds has been reduced, and alternative fat sources are of increasing importance. In this paper...

  17. Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.

    Science.gov (United States)

    Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin

    2017-08-01

    Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus

  18. Saturated and trans fats

    National Research Council Canada - National Science Library

    Shader, Richard I

    2014-01-01

    ... Original Pancake Mix plus ingredients suggested by the recipe: 2 g saturated fat (SF) and no trans fatty acids or trans fat (TFA); bacon, Oscar Mayer Lower Sodium Bacon: 2.5 g SF and no TFA; sausages, Jimmy Dean Original Pork Sausage Links: 8 g SF and no TFA; potatoes, Ore-Ida Mini Tater Tots: 2 g SF and no TFA; and nondairy creamer, Nestlé Coffee-...

  19. Physiological adaptations induced by swimming in mice fed a high fat diet.

    Science.gov (United States)

    Nogueira, Pedro Augusto Silva; Pereira, Miriam Pimenta; Soares, Jeferson José Gomes; Filho, Anderson Ferraz Norton; Tanimoto, Izadora Mayumi Fujinami; Fonseca, Ivana Alice Teixeira; Avelar, Homero Oliveira; Botelho, Francoise Vasconcelos; Roever, Leonardo; Vieira, Alexandre Antônio; Zanon, Renata Graciele

    2017-06-01

    This study examined physiological variables of animals fed with a high-fat diet (HFD) or with a normal diet (ND) subjected to swimming at low and moderate level. Over 16 weeks, a group of animals was fed with HFD or ND, and at the 8 weeks, they started swimming with 50% or 80% of the maximum load achieved in the progressive work test. Weekly, body weight and the amount of ingested food were registered. The glycemic level was measured at the beginning, middle and at the end of the experiment. Adipose tissue, gastrocnemius muscles and hearts were collected for morphometry. The results showed that the animals fed an HFD had a minor caloric intake; however, the HFD increased body weight and adiposity, likely causing cardiac hypertrophy and an increase in the glycemic level. In this context, swimming with an 80% load contributed positively to weight control, adiposity, glycemic level, to control cardiac hypertrophy and induce hypertrophy in the gastrocnemius muscle. All parameters assessed showed better results for the ND animals. Therefore, the importance of fat consumption was emphasized in relation to obesity onset. The practice of swimming with an 80% load produced greater benefits than swimming with a 50% load for overweight treatment.

  20. Diets containing corn oil, coconut oil and cholesterol alter ventricular hypertrophy, dilatation and function in hearts of rats fed copper-deficient diets.

    Science.gov (United States)

    Jenkins, J E; Medeiros, D M

    1993-06-01

    Cardiac hypertrophy and function were evaluated in rats fed diets containing deficient, marginal or adequate levels of copper. The fat concentration of the diets was either 10 g/100 g corn oil, 10 g/100 g coconut oil or 10 g/100 g coconut oil + 1 g/100 g added cholesterol. Left ventricular (LV) wall thickening of hearts in rats fed copper-deficient diets was characterized by greater (P oil. Rats fed the copper-deficient diet with coconut oil + cholesterol had LV chamber volumes that were twofold larger than those of rats fed the copper-deficient diet with coconut oil or corn oil. Copper deficiency reduced LV chamber volume only in rats fed coconut oil + cholesterol. Cardiac LV end diastolic pressure in rats fed copper-deficient diets was twofold larger than in copper-adequate and copper-marginal groups fed corn oil or coconut oil. Hearts from rats fed the copper-deficient diet with corn oil compared with those from rats fed the copper-deficient diet with coconut oil + cholesterol had greater right ventricular (RV) and LV end diastolic pressures, LV pressures and LV and RV maximal rates of positive pressure development. Our data suggest that cardiac adaptations in rats fed copper-deficient diets are influenced by dietary fat type: 1) hearts of rats fed the copper-deficient diet with corn oil were concentrically hypertrophied, whereas cardiac contractility was maintained in the presence of high preload; 2) preload and contractility in hearts of coconut oil-fed rats was greater than cardiac response to cholesterol addition to the coconut oil diet; 3) hearts in copper-deficient rats fed coconut oil + cholesterol exhibited eccentric hypertrophy and ventricular dysfunction.

  1. Myocardial hypertrophy in the recipient with twin-to-twin transfusion syndrome

    DEFF Research Database (Denmark)

    Jeppesen, D.L.; Jorgensen, F.S.; Pryds, O.A.

    2008-01-01

    In a set of monochorionic-diamniotic twins with twin-to-twin transfusion syndrome, systemic hypertension and biventricular myocardial hypertrophy were found in the recipient. The infant developed mild respiratory distress. A partial exchange transfusion was performed because of polycytaemia. Blood...... pressure measurements revealed persistent systemic hypertension. Biventricular hypertrophy was demonstrated by echocardiography. Blood pressure normalised after treatment with Nifedipine and the cardiac hypertrophy subsided over the following weeks. A potential contributing mechanism is intrauterine...

  2. Asymmetric left ventricular hypertrophy associated with morbid obesity mimicking familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wong, Raymond Ching-Chiew; Tan, Kong Bing

    2014-12-01

    Asymmetric septal hypertrophy with systolic anterior motion of the mitral valve is frequently a phenotypic, but not pathognomonic, expression of genetic hypertrophic cardiomyopathy (HCM) with or without obstruction. It can, however, be associated nonspecifically with other forms of increased left ventricular (LV) afterload. We herein report the case of a young man with obesity cardiomyopathy and heart failure who presented with asymmetric septal hypertrophy and marked LV hypertrophy, and endomyocardial biopsy ruled out genetic HCM.

  3. Myocardial hypertrophy in the recipient with twin-to-twin transfusion syndrome

    DEFF Research Database (Denmark)

    Jeppesen, D.L.; Jorgensen, F.S.; Pryds, O.A.

    2008-01-01

    pressure measurements revealed persistent systemic hypertension. Biventricular hypertrophy was demonstrated by echocardiography. Blood pressure normalised after treatment with Nifedipine and the cardiac hypertrophy subsided over the following weeks. A potential contributing mechanism is intrauterine......In a set of monochorionic-diamniotic twins with twin-to-twin transfusion syndrome, systemic hypertension and biventricular myocardial hypertrophy were found in the recipient. The infant developed mild respiratory distress. A partial exchange transfusion was performed because of polycytaemia. Blood...

  4. Role of Ca2+ signaling in skeletal muscle hypertrophy and atrophy

    National Research Council Canada - National Science Library

    Ito, Naoki; Takeda, Shin’ichi

    2015-01-01

    .... Although intracellular signaling molecules and pathways underlying the regulation of protein synthesis/degradation and subsequent muscle hypertrophy/atrophy are well studied, upstream regulators are largely unknown...

  5. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

    Science.gov (United States)

    Li, Chen; Chen, Zhongxiu; Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  6. Cardiac hypertrophy induced by active Raf depends on Yorkie-mediated transcription.

    Science.gov (United States)

    Yu, Lin; Daniels, Joseph P; Wu, Huihui; Wolf, Matthew J

    2015-02-03

    Organ hypertrophy can result from enlargement of individual cells or from cell proliferation or both. Activating mutations in the serine-threonine kinase Raf cause cardiac hypertrophy and contribute to Noonan syndrome in humans. Cardiac-specific expression of activated Raf also causes hypertrophy in Drosophila melanogaster. We found that Yorkie (Yki), a transcriptional coactivator in the Hippo pathway that regulates organ size, is required for Raf-induced cardiac hypertrophy in flies. Although aberrant activation of Yki orthologs stimulates cardiac hyperplasia in mice, cardiac-specific expression of an activated mutant form of Yki in fruit flies caused cardiac hypertrophy without hyperplasia. Knockdown of Yki caused cardiac dilation without loss of cardiomyocytes and prevented Raf-induced cardiac hypertrophy. In flies, Yki-induced cardiac hypertrophy required the TEA domain-containing transcription factor Scalloped, and, in mammalian cells, expression of mouse Raf(L613V), an activated form of Raf with a Noonan syndrome mutation, increased Yki-induced Scalloped activity. Furthermore, overexpression of Tgi (a Tondu domain-containing Scalloped-binding corepressor) in the fly heart abrogated Yki- or Raf-induced cardiac hypertrophy. Thus, crosstalk between Raf and Yki occurs in the heart and can influence Raf-mediated cardiac hypertrophy. Copyright © 2015, American Association for the Advancement of Science.

  7. Isorhamnetin protects against cardiac hypertrophy through blocking PI3K-AKT pathway.

    Science.gov (United States)

    Gao, Lu; Yao, Rui; Liu, Yuzhou; Wang, Zheng; Huang, Zhen; Du, Binbin; Zhang, Dianhong; Wu, Leiming; Xiao, Lili; Zhang, Yanzhou

    2017-05-01

    Isorhamnetin, a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L., is well known for its anti-inflammatory, anti-oxidative, anti-adipogenic, anti-proliferative, and anti-tumor activities. However, the role of isorhamnetin in cardiac hypertrophy has not been reported. The aims of the present study were to find whether isorhamnetin could alleviate cardiac hypertrophy and to define the underlying molecular mechanisms. Here, we investigated the effects of isorhamnetin (100 mg/kg/day) on cardiac hypertrophy induced by aortic banding in mice. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. Our data demonstrated that isorhamnetin could inhibit cardiac hypertrophy and fibrosis 8 weeks after aortic banding. The results further revealed that the effect of isorhamnetin on cardiac hypertrophy was mediated by blocking the activation of phosphatidylinositol 3-kinase-AKT signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes confirmed that isorhamnetin could attenuate cardiomyocyte hypertrophy induced by angiotensin II, which was associated with phosphatidylinositol 3-kinase-AKT signaling pathway. In conclusion, these data indicate for the first time that isorhamnetin has protective potential for targeting cardiac hypertrophy by blocking the phosphatidylinositol 3-kinase-AKT signaling pathway. Thus, our study suggests that isorhamnetin may represent a potential therapeutic strategy for the treatment of cardiac hypertrophy and heart failure.

  8. Management of Unilateral Masseter Hypertrophy and Hypertrophic Scar—A Case Report

    Directory of Open Access Journals (Sweden)

    Naresh Shetty

    2012-01-01

    Full Text Available Masseter muscle hypertrophy is a rare condition of idiopathic cause. It clinically presents as an enlargement of one or both masseter muscles. Most patients complain of facial asymmetry; however, symptoms such as trismus, protrusion, and bruxism may also occur. Several treatment options reported for masseter hypertrophy are present, which range from simple pharmacotherapy to more invasive surgical reduction. Keloid scar with unilateral masseter hypertrophy is a rarely seen in clinical practice. This paper reports a case of unilateral masseter hypertrophy with keloid scar in the angle of the mandible for which surgical treatment was rendered to the patient by using a single approach.

  9. Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Leonidas Apostolidis

    Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

  10. Robust multipoint water-fat separation using fat likelihood analysis.

    Science.gov (United States)

    Yu, Huanzhou; Reeder, Scott B; Shimakawa, Ann; McKenzie, Charles A; Brittain, Jean H

    2012-04-01

    Fat suppression is an essential part of routine MRI scanning. Multiecho chemical-shift based water-fat separation methods estimate and correct for Bo field inhomogeneity. However, they must contend with the intrinsic challenge of water-fat ambiguity that can result in water-fat swapping. This problem arises because the signals from two chemical species, when both are modeled as a single discrete spectral peak, may appear indistinguishable in the presence of Bo off-resonance. In conventional methods, the water-fat ambiguity is typically removed by enforcing field map smoothness using region growing based algorithms. In reality, the fat spectrum has multiple spectral peaks. Using this spectral complexity, we introduce a novel concept that identifies water and fat for multiecho acquisitions by exploiting the spectral differences between water and fat. A fat likelihood map is produced to indicate if a pixel is likely to be water-dominant or fat-dominant by comparing the fitting residuals of two different signal models. The fat likelihood analysis and field map smoothness provide complementary information, and we designed an algorithm (Fat Likelihood Analysis for Multiecho Signals) to exploit both mechanisms. It is demonstrated in a wide variety of data that the Fat Likelihood Analysis for Multiecho Signals algorithm offers highly robust water-fat separation for 6-echo acquisitions, particularly in some previously challenging applications. Copyright © 2011 Wiley-Liss, Inc.

  11. Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling.

    Science.gov (United States)

    Gitau, Samuel Chege; Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Liang, Haihai; Qian, Ming; Lv, Lifang; Li, Tianshi; Xu, Bozhi; Wang, Zhiguo; Zhang, Yong; Xu, Chaoqian; Lu, Yanjie; Du, Zhiming; Shan, Hongli; Yang, Baofeng

    2015-12-01

    Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction (TAC) or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin (10 mg·kg(-1)·d(-1)); the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II (10 nmol·L(-1)) was treated with the human equivalent of low (10 or 100 μmol·L(-1)) and high (1000 μmol·L(-1)) aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, β-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and b-type natriuretic peptide (BNP). Aspirin efficiently reversed the upregulation of β-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3β. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of β-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin.

  12. The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

    Science.gov (United States)

    Marcotte, George R.; West, Daniel W.D.; Baar, Keith

    2016-01-01

    In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

  13. Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection.

    Science.gov (United States)

    Marongiu, Fabio; Marongiu, Michela; Contini, Antonella; Serra, Monica; Cadoni, Erika; Murgia, Riccardo; Laconi, Ezio

    2017-03-14

    To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

  14. Acute colonic obstruction due to benign prostatic hypertrophy.

    LENUS (Irish Health Repository)

    Mac Giobuin, S

    2012-02-01

    A seventy two year old man presented to the Emergency Department with clinical features of colonic obstruction. Subsequent radiological investigations confirmed this impression and revealed the aetiology to be compression of the sigmoid colon against the sacrum by a massively distended urinary bladder. Chronic urinary retention due to benign prostatic hypertrophy is an extremely unusual cause of large bowel obstruction. Little in this patient\\'s clinical findings suggested this aetiology. We reviewed the literature in this area and highlight the benefits of CT scanning over contrast studies.

  15. Painful parotid hypertrophy with bulimia: a report of medical management.

    Science.gov (United States)

    Park, Kelly K; Tung, Rebecca C; de Luzuriaga, Arlene Ruiz

    2009-06-01

    In eating disorders, such as bulimia nervosa, body image disturbance often extends beyond the realm of weight and shape into the dermatologic spectrum. While commonly associated conditions due to binging and self-induced vomiting include cutaneous entities (e.g., Russell's sign, acne, alopecia and hypertrichosis) and oral pathologies (e.g., enamel erosion, caries and mild parotid hypertrophy), a rare but troubling manifestation is disfiguring parotid enlargement (sialoadenomegaly). This article presents a case of painful sialoadenomegaly associated with hyperamylasemia in a bulimic patient successfully managed with pilocarpine.

  16. adenoid and tonsils hypertrophy − symptoms and treatment

    Directory of Open Access Journals (Sweden)

    iwona Łapińska

    2016-12-01

    Full Text Available Introduction. Adenoid and tonsil hypertrophy is widespread in the pediatric population, affecting primarily younger children,aged 3 to 6 years. in 1884, a German pathologist, von Waldeyer-hartz, first described clusters of lymphoid tissue in mucosa ofthe throat, which he named facial lymphatic ring, known today as Waldeyer’s tonsillar ring. Waldeyer’s ring plays a significantrole in the development of immune response by allowing the contact of the immune system with multiple antigens and thus,enabling the development of the specific immunological response. the main points of contact of the body with the externalenvironment are the mucous membranes of the digestive and respiratory systems. Waldeyer’s ring, being at the opening of bothsystems, has a particular role in the development of immune response, especially during the first years of life.Aim. the aim of the study was to analyze the symptoms presented by children hospitalized in the Clinic of pediatric otolaryngology of the medical University of Warsaw that had been qualified for the surgical removal of the adenoid and/or tonsils.Material and methods. All the patients underwent physical examination, and filled in a survey. the study included 59 hospitalized patients, 2 of which refused to disclose the symptoms associated with adenoid and tonsil hypertrophy that was diagnosedin them.Results. the study involved 59 children aged from 2 to 13 years old. the mean age was 6.2 years. the patients were qualifiedfor adenoidectomy or adenotonsillotomy. in 26 cases, at least one of the parents of the patient smoked in the presence of thechild. 28 patients reported nasal obstruction, and 29 denied such symptoms. As many as 41 patients (71.9% reported snoringduring sleep. 45 patients (78.9% breathed through the mouth. Based on the medical history collected from the parents, 22 patients (37.3% had upper respiratory tract infection at least once a month, 7 patients – every two weeks, 9 – every

  17. Correction of Brassiere Strap Grooves with Fat Injections.

    Science.gov (United States)

    Ergün, Selma Sönmez; Baygöl, Emre Gönenç; Kayan, Reşit Burak; Kuzu, İsmail Melih; Akman, Onur

    2015-07-01

    The size and weight of hypertrophied breast can cause both physical and psychological problems. Although the majority of these problems can be solved with breast reduction surgery, the particular problem of development of brassiere strap grooves on the shoulders due to the weight of the breasts cannot be corrected with this method. Breast reduction surgery focuses only on the increased dimensions of breasts: fullness of the thoracic wall lateral to the breasts, as well as the appearance of brassiere strap grooves, need to be taken into consideration to obtain a better upper body image. Therefore, we present a series of 10 female patients who were treated with fat injections for the correction of brassiere strap grooves. Reduction mammaplasty and fat injections into the brassiere strap grooves were performed during the same session. Dramatic changes are obtained with judicious placement of fat into the bra strap grooves. A more aesthetic and harmonious look can be obtained with using these combined aesthetic procedures in appropriately selected patients. 4 Therapeautic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  18. Measurement of visceral fat: should we include retroperitoneal fat?

    Directory of Open Access Journals (Sweden)

    Chi-Sheng Hung

    Full Text Available OBJECTIVE: Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes. METHODS: We enrolled 432 adult participants (153 men and 279 women in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas. RESULTS: Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR, 5.651, p<0.05 and the number of metabolic abnormalities (p<0.05. Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r =  -0.244, P<0.05, and leptin (r = 0.323, p<0.05, but not plasma renin or aldosterone concentrations. During the 2.94 ± 0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR 1.62, p = 0.003 and peritoneal fat area (HR 1.62, p = 0.009, but not subcutaneous fat area (p = 0.14 were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment. CONCLUSIONS: Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.

  19. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

    Directory of Open Access Journals (Sweden)

    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  20. Fat Grams: How to Track Your Dietary Fat

    Science.gov (United States)

    Healthy Lifestyle Nutrition and healthy eating To track how much fat I eat each day, should I focus on ... 30, 2016 Original article: http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/fat-grams/faq- ...

  1. Electrocardiographic Left Ventricular Hypertrophy Among Gambian Diabetes Mellitus Patients.

    Science.gov (United States)

    Jobe, M; Kane, A; Jones, J C; Pessinaba, S; Nkum, B C; Abdou Ba, S; Nyan, O A

    2015-03-01

    The global prevalence of diabetes and its complications is increasing worldwide. Its role in coronary heart disease has been linked with the presence of left ventricular hypertrophy (LVH). The present study aims to determine the prevalence of electrocardiographic left ventricular hypertrophy (ECG-LVH) in adult diabetic subjects, its epidemiological and clinical correlates. A descriptive cross-sectional study involving 534 patients was conducted at the Edward Francis Small Teaching Hospital (formerly Royal Victoria Teaching Hospital), The Gambia. Four hundred and forty patients were included using a standard questionnaire. Anthropometry, laboratory investigations and electrocardiogram were carried out. We used the Lewis, Cornell, and Sokolow-Lyon Voltage criteria to define ECG-LVH. Minitab™ statistical software version 13.20 was used for analysis. 146 (35.2%) patients had ECG-LVH using all 3 criteria and this prevalence was higher among women being 116 (79.5%). A generally high prevalence of overweight (155/37.4%) and obesity (119/28.6%) was observed among study participants, and both clinic-day systolic and diastolic blood pressure (BP) were significantly higher in those with ECG-LVH. Poor diabetes control was observed in both groups. There was a high prevalence of ECG-LVH and it is especially so with combining multiple criteria, hence the need for screening. Clinic-day hypertension was associated with ECG-LVH hence the need for diagnosing and aggressive treatment of hypertension in patients with diabetes mellitus.

  2. Proteinuria and glomerular hypertrophy in extremely low-birthweight children.

    Science.gov (United States)

    Hayashi, Asako; Santo, Yoko; Satomura, Kenichi

    2014-12-01

    Of late, there is an increased awareness of the frequent occurrence of hypertension or proteinuria in adults born at low birthweight. We retrospectively studied five children born with extremely low birthweight (ELBW) who were first diagnosed with proteinuria in a school urinary screening program. These children were born at 23-25 weeks of gestation, and their birthweight was 532-732 g. Proteinuria was identified in all the subjects in a school urinary screening program when they were 6-15 years old. Renal biopsy showed diffuse increase in glomerular size, consistent with glomerular hypertrophy. There were no findings of mesangial proliferation or glomerular sclerosis. All the subjects had a marked decrease in proteinuria after angiotensin receptor blocker (ARB) treatment. Reduced number of glomeruli associated with prematurity was speculated to have caused compensatory glomerular hyperfiltration, hypertrophy, and hypertension in children born with ELBW when they developed proteinuria. ARB could have been effective for proteinuria by reducing glomerular hypertension. Physicians should be aware of proteinuria in children born with ELBW because there is an increasing number of ELBW survivors as a result of advances in medical technology. © 2014 Japan Pediatric Society.

  3. Fat utilization during exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Watt, Peter W.; Richter, Erik

    2001-01-01

    % carbohydrate) and six consumed a carbohydrate-rich diet (20 % fat, 65 % carbohydrate). After 7 weeks of training and diet, 60 min of bicycle exercise was performed at 68 +/- 1 % of maximum oxygen uptake. During exercise [1-(13)C]palmitate was infused, arterial and venous femoral blood samples were collected......, and blood flow was determined by the thermodilution technique. Muscle biopsy samples were taken from the vastus lateralis muscle before and after exercise. 3. During exercise, the respiratory exchange ratio was significantly lower in subjects consuming the fat-rich diet (0.86 +/- 0.01, mean +/- S.E.M.) than...... the fat-rich diet. Whole-body plasma FA oxidation (determined by comparison of (13)CO(2) production and blood palmitate labelling) was 55-65 % of total lipid oxidation, and was higher after the fat-rich diet than after the carbohydrate-rich diet (13.5 +/- 1.2 vs. 8.9 +/- 1.1 micromol min(-1) kg(-1); P

  4. Subcutaneous encapsulated fat necrosis

    DEFF Research Database (Denmark)

    Aydin, Dogu; Berg, Jais O

    2016-01-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help...

  5. Fats for diabetics. (Letter).

    NARCIS (Netherlands)

    Katan, M.B.

    1994-01-01

    Opinion. Comments on the treatment of type 2 diabetes from the interaction between nature and nurture. Effective form of treatment for type 2 diabetes; Composition of the diet for diabetics; Identification of unsaturated fats in the diabetic diet; Risks faced by diabetic patients.

  6. That Fat Cat

    Science.gov (United States)

    Lambert, Phyllis Gilchrist

    2012-01-01

    This activity began with a picture book, Nurit Karlin's "Fat Cat On a Mat" (HarperCollins; 1998). The author and her students started their project with a 5-inch circular template for the head of their cats. They reviewed shapes as they drew the head and then added the ears and nose, which were triangles. Details to the face were added when…

  7. Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

    NARCIS (Netherlands)

    van Borren, Marcel M. G. J.; Vos, Marc A.; Houtman, Marien J. C.; Antoons, Gudrun; Ravesloot, Jan H.

    2013-01-01

    Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes

  8. Second statement of the working group on electrocardiographic diagnosis of left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Bacharova, Ljuba; Estes, E Harvey; Bang, Lia E

    2011-01-01

    The Working Group on Electrocardiographic Diagnosis of Left Ventricular Hypertrophy, appointed by the Editor of the Journal of Electrocardiology, presents the alternative conceptual model for the ECG diagnosis of left ventricular hypertrophy (LVH). It is stressed that ECG is a record of electrical...

  9. Dose-dependent difference of nuclear receptors involved in murine liver hypertrophy by piperonyl butoxide.

    Science.gov (United States)

    Sakamoto, Yohei; Yoshida, Midori; Tamura, Kei; Takahashi, Miwa; Kodama, Yukio; Inoue, Kaoru

    2015-12-01

    Nuclear receptors play important roles in chemically induced liver hypertrophy in rodents. To clarify the involvement of constitutive androstane receptor (CAR) and other nuclear receptors in mouse liver hypertrophy induced by different doses of piperonyl butoxide (PBO), wild-type and CAR-knockout mice were administered PBO (200, 1,000, or 5,000 ppm) in the basal diet for 1 week. Increased liver weight and diffuse hepatocellular hypertrophy were observed at 5,000 ppm for both genotypes, accompanied by increased Cyp3a11 mRNA and CYP3A protein expression, suggesting that CAR-independent pathway, possibly pregnane X receptor (PXR), plays a major role in the induction of hypertrophy. Moreover, wild-type mice at 5,000 ppm showed enhanced hepatocellular hypertrophy and strong positive staining for CYP2B in the centrilobular area, suggesting the localized contribution of CAR. At 1,000 ppm, only wild-type mice showed liver weight increase and centrilobular hepatocellular hypertrophy concurrent with elevated Cyp2b10 mRNA expression and strong CYP2B staining, indicating that CAR was essential at 1,000 ppm. We concluded that high-dose PBO induced hypertrophy via CAR and another pathway, while lower dose of PBO induced a pathway mediated predominantly by CAR. The dose-responsiveness on liver hypertrophy is important for understanding the involvement of nuclear receptors.

  10. Regression of Copper-Deficient Heart Hypertrophy: Reduction in the Size of Hypertrophic Cardiomyocytes

    Science.gov (United States)

    Dietary copper deficiency causes cardiac hypertrophy and its transition to heart failure in a mouse model. Copper repletion results in a rapid regression of cardiac hypertrophy and prevention of heart failure. The present study was undertaken to understand dynamic changes of cardiomyocytes in the hy...

  11. Relationship between electrocardiographic features and distribution of hypertrophy in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Tetsuya; Nakamura, Kazufumi; Yamanari, Hiroshi; Ohe, Tohru [Okayama Univ. (Japan). School of Medicine; Yoshinouchi, Takeo

    1998-07-01

    To evaluate the relationship between the distribution of hypertrophy and the electrocardiographic findings in patients with hypertrophic cardiomyopathy (HCM), 54 HCM patients were studied using magnetic resonance imaging. The patients were divided into 4 groups according to hypertrophic patterns: hypertrophy only at the apex (group I, n=12); hypertrophy in both the apex and base (group II, n=20); hypertrophy only at the base with asymmetric septal hypertrophy (ASH) (group IIIa, n=17); and hypertrophy only at the base without ASH (group IIIb, n=5). Abnormal Q waves in leads II, III and aV{sub F} were found in 1/12, 3/20, 10/17 and 0/5, respectively, and in leads I and aV{sub L} they were found in 1/12, 8/20, 4/17 and 1/5, respectively. The largest negative T waves (mm) were found in group I (group I vs group II vs group IIIa vs group IIIb: 15.2{+-}5.3, 8.2{+-}6.1, 1.6{+-}2.0, 0.8{+-}1.3, respectively). The largest positive T waves (mm) were identified in group IIIb (3.8{+-}3.0, 6.8{+-}3.2, 5.8{+-}3.6, 9.3{+-}2.1, respectively). The presence of abnormal Q waves reflected regional hypertrophy in HCM patients but the configuration of T waves represented the difference in the localization of hypertrophy between the basal and apical segments. (author)

  12. Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Mølgaard, Søren; Faricelli, Barbara; Salomonsson, Max

    2016-01-01

    .  Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible...... loci of this increased, hypertrophy-associated vulnerability....

  13. Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Yao

    2017-04-01

    Full Text Available Cardiac hypertrophy is a major risk factor for heart failure, which are among the leading causes of human death. Gastrodin is a small molecule that has been used clinically to treat neurological and vascular diseases for many years without safety issues. In the present study, we examined protective effect of gastrodin against cardiac hypertrophy and explored the underlying mechanism. Phenylephrine and angiotensin II were used to induce cardiac hypertrophy in a mouse model and a cultured cardiomyocyte model. Gastrodin was found to alleviate the cardiac hypertrophy in both models. Mechanistically, gastrodin attenuated the store-operated Ca2+ entry (SOCE by reducing the expression of STIM1 and Orai1, two key proteins in SOCE, in animal models as well as in cultured cardiomyocyte model. Furthermore, suppressing SOCE by RO2959, Orai1-siRNAs or STIM1-siRNAs markedly attenuated the phenylephrine-induced hypertrophy in cultured cardiomyocyte model. Together, these results showed that gastrodin inhibited cardiac hypertrophy and it also reduced the SOCE via its action on the expression of STIM1 and Orai1. Furthermore, suppression of SOCE could reduce the phenylephrine-induced cardiomyocyte hypertrophy, suggesting that SOCE-STIM1-Orai1 is located upstream of hypertrophy.

  14. Intra-abdominal fat: Comparison of computed tomography fat ...

    African Journals Online (AJOL)

    Background: Intra-abdominal fat is an important factor in determining the metabolic syndrome/insulin resistance, and thus the risk of diabetes and ischaemic heart disease. Computed Tomography (CT) fat segmentation represents a defined method of quantifying intra-abdominal fat, with attendant radiation risks.

  15. Effect Of Fat Source And Vitamin E Supplimentation On Fat ...

    African Journals Online (AJOL)

    The effect of different sources of fat on carcass characteristics, fatty acid composition of broilers and the interactive effect of fat source and vitamin E on keeping quality of broiler thigh meat were evaluated. The four dietary treatments were the control (No fat inclusion); palm oil; groundnut oil and palm kernel oil. The diets ...

  16. A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy

    National Research Council Canada - National Science Library

    Espen E. Spangenburg; Derek Le Roith; Chris W. Ward; Sue C. Bodine

    2008-01-01

    ...-I), which is thought to be a critical step in the induction of muscle hypertrophy. To determine the role of the IGF-I receptor in load-induced skeletal muscle hypertrophy, we utilized a transgenic mouse model (MKR...

  17. Diastolic function alteration mechanisms in physiologic hypertrophy versus pathologic hypertrophy are elucidated by model-based Doppler E-wave analysis

    OpenAIRE

    Zhu, Simeng; Morrell, Thomas; Apor, Astrid; Merkely, Béla; Vágó, Hajnalka; Tóth, Attila; Ghosh, Erina; Kovács, Sándor J.

    2014-01-01

    Athletic training can result in increased left ventricular (LV) wall thickness, termed physiologic hypertrophy (PhH). By contrast, pathologic hypertrophy (PaH) can be due to hypertension, aortic stenosis, or genetic mutation causing hypertrophic cardiomyopathy (HCM). Because morphologic (LV dimension, wall thickness, mass, etc.) and functional index similarities (LV ejection fraction, cardiac output, peak filling rate, etc.) limit diagnostic specificity, ability to differentiate between PhH a...

  18. Figuring Out Fat and Calories

    Science.gov (United States)

    ... our growth and activities — everything from solving a math problem to racing up and down the soccer ... saturated fat and trans fat raise blood cholesterol levels, increasing a person's chances of developing heart disease, ...

  19. Tear me down: Role of calpain in the development of cardiac ventricular hypertrophy

    Science.gov (United States)

    Patterson, Cam; Portbury, Andrea; Schisler, Jonathan C.; Willis, Monte S.

    2011-01-01

    Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize the molecular mechanisms by which calpain inhibition has been shown to modulate the development of cardiac (specifically ventricular) hypertrophy. The context within which calpain inhibition might be developed for therapeutic intervention of cardiac hypertrophy is then discussed. PMID:21817165

  20. Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy

    Science.gov (United States)

    Li, Jun; Qi, Man; Li, Changming; Shi, Dan; Zhang, Dasheng; Xie, Duanyang; Yuan, Tianyou; Feng, Jing; Liu, Yi; Liang, Dandan; Xu, Xinran; Chen, Jinjin; Xu, Liang; Zhang, Hong; Ye, Jiangchuan; Lv, Fei; Huang, Jian; Peng, Luying; Chen, Yi-Han

    2014-01-01

    Pathological cardiac hypertrophy is an inevitable forerunner of heart failure. Regardless of the etiology of cardiac hypertrophy, cardiomyocyte mitochondrial alterations are always observed in this context. The translocases of mitochondrial outer membrane (Tom) complex governs the import of mitochondrial precursor proteins to maintain mitochondrial function under pathophysiological conditions; however, its role in the development of pathological cardiac hypertrophy remains unclear. Here, we showed that Tom70 was downregulated in pathological hypertrophic hearts from humans and experimental animals. The reduction in Tom70 expression produced distinct pathological cardiomyocyte hypertrophy both in vivo and in vitro. The defective mitochondrial import of Tom70-targeted optic atrophy-1 triggered intracellular oxidative stress, which led to a pathological cellular response. Importantly, increased Tom70 levels provided cardiomyocytes with full resistance to diverse pro-hypertrophic insults. Together, these results reveal that Tom70 acts as a molecular switch that orchestrates hypertrophic stresses and mitochondrial responses to determine pathological cardiac hypertrophy. PMID:25022898

  1. Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, H.J.; Ouyang, W.; Liu, J.H.; Sun, Y.G.; Hu, R.; Huang, L.H.; Xian, J.L. [Southern Medical University, Department of Nuclear Medicine, Zhujiang Hospital, Guangzhou, China, Department of Nuclear Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Jing, C.F.; Zhou, M.J. [Sun Yat-Sen University, South China Sea Marine Biotechnology, National Engineering Research Center, Guangzhou, China, National Engineering Research Center, South China Sea Marine Biotechnology, Sun Yat-Sen University, Guangzhou (China)

    2014-04-11

    Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

  2. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy

    Science.gov (United States)

    Spagnolli, Ester; Ernande, Laura; Thoonen, Robrecht; Kolodziej, Starsha A.; Leyton, Patricio A.; Cheng, Juan; Tainsh, Robert E. T.; Mayeur, Claire; Rhee, David K.; Wu, Mei. X.; Scherrer-Crosbie, Marielle; Buys, Emmanuel S.; Zapol, Warren M.; Bloch, Kenneth D.; Bloch, Donald B.

    2016-01-01

    Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID:26873969

  3. Left ventricular hypertrophy: The relationship between the electrocardiogram and cardiovascular magnetic resonance imaging.

    Science.gov (United States)

    Bacharova, Ljuba; Ugander, Martin

    2014-11-01

    Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. © 2014 Wiley Periodicals, Inc.

  4. Protect Your Heart: Choose Healthy Fats

    Science.gov (United States)

    ... by eating less trans fat, saturated fat and cholesterol. Sources of saturated fat • bacon and bacon grease • high-fat dairy products, • butter such as cheese, cream, • chitterlings ice cream, whole milk, 2% milk, ...

  5. Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population.

    Science.gov (United States)

    Atilla, Mahmut Huntürk; Özdaş, Sibel; Özdaş, Talih; Baştimur, Sibel; Muz, Sami Engin; Öz, Işılay; Kurt, Kenan; İzbirak, Afife; Babademez, Mehmet Ali; Vatandaş, Nilgün

    2017-08-01

    Adenoid hypertrophy is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with adenoid hypertrophy. The aim of this study is to investigate the association of single nucleotide polymorphisms in the Ugrp2 gene with adenoid hypertrophy and its related phenotypes. A total of 219 children, comprising 114 patients suffering from adenoid hypertrophy and 105 healthy patients without adenoid hypertrophy, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing. We identified four single nucleotide polymorphisms (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of adenoid hypertrophy compared with the controls (p=0.012, p=0.009, p=0.013, and p=0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with adenoid hypertrophy (four single nucleotide polymorphisms ordered from 5' to 3'; p=0.0001). Polymorfism-Polymorfism interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to adenoid hypertrophy, as well as an increased chance of its diagnosis (p<0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of adenoid hypertrophy with asthma and adenoid hypertrophy with allergies (p=0.003 and p=0.0007, respectively). Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy

  6. Fat and bone.

    Science.gov (United States)

    Reid, Ian R

    2010-11-01

    Body weight is a principal determinant of bone density and fracture risk, and adipose tissue mass is a major contributor to this relationship. In contrast, some recent studies have argued that "fat mass after adjustment for body weight" actually has a deleterious effect on bone, but these analyses are confounded by the co-linearity between the variables studied, and therefore have produced misleading results. Mechanistically, fat and bone are linked by a multitude of pathways, which ultimately serve the function of providing a skeleton appropriate to the mass of adipose tissue it is carrying. Adiponectin, insulin/amylin/preptin, leptin and adipocytic estrogens are all likely to be involved in this connection. In the clinic, the key issues are that obesity is protective against osteoporosis, but underweight is a major preventable risk factor for fractures. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Brown Fat Cell Isolation

    OpenAIRE

    sprotocols

    2014-01-01

    Author: C.R. Kahn ### 1.) ISOLATION AND PRIMARY CULTURE OF BROWN FAT PREADIPOCYTES ### Rationale: To prepare primary brown preadipocytes for immortalization: useful for metabolic studies from knockout mice. This consists of the following five protocols. References: Fasshauer, M., J. Klein, K M. Kriauciunas, K. Ueki, M.Benito, and C.R. Kahn. 2001. Essential role of insulin substrate 1 in differentiation of brown adipocytes. *Mol Cell Biol* 21: 319-329. Fasshauer, M....

  8. Clinical Importance of Epicardial Fat Thickness Defining in Obese Patients

    Directory of Open Access Journals (Sweden)

    Galina A. Chumakova, PhD, ScD¹´³

    2012-09-01

    Full Text Available Obesity is a global epidemic characteristic of the 21st century; therefore, studying the subclinical markers of coronary atherosclerosis in overweight patients is current and relevant. With weight increase, hypertrophy and hyperplasia of adipocytes occur not only in the abdominal area, but also in the ectopic local fat depots, including the epicardial ones. As the myocardium and coronary arteries are anatomically related, hormonally active epicardial fat seems to be a pathologic link between obesity and coronary heart disease (CHD. The objective of this research is to study the relationship between epicardial adiposity and abdominal obesity with metabolic risk factors and visceral fat adipokines. The influence of epicardial fat thickness (EFT and waist circumference (WC on the risk of development of significant coronary atherosclerosis in obese patients with CHD was studied (138 men, 55.47±9.07 years and BMI 35.2±5.2 kg/m². The ROC analysis reveals that EFT is more informative in diagnosing significant stenoses (≥70 %: sensitivity of the given marker constituted 80.4 %, specificity – 67.6 % (cut-off value=6 mm. On comparison of the epicardial and abdominal adiposity as predictors of coronary atherosclerosis, EFT was found to be more significant than WC. In patients with CHD, the increase in EFT is associated with the more serious involvement of the coronary arteries, whereas the WC analysis did not establish similar regularities. Evaluation of EFT in obese patients can be used as a noninvasive marker indicative of the presence of subclinical stenoses of the coronary arteries.

  9. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Hesse, Birger; Meyer, Christian; Nielsen, Flemming S

    2004-01-01

    with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123+/-7/65+/-9 mmHg. Compared......The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary...... disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified...

  10. Consideration of Drug Therapy in Benign Prostatic Hypertrophy

    Directory of Open Access Journals (Sweden)

    G. Diamantis

    2015-01-01

    Full Text Available Benign prostatic hypertrophy (BPH has become a major global health problem both in its frequency by which it determines the complications and the problems of diagnosis and treatment it requires. BPH is a heterogeneous disease. The symptoms attributed to BPH may have other coexisting causes and growth factors both androgen-dependent and independent, which promotes prostate enlargement. It is well known that prostate size correlates poorly with the symptoms so that reducing prostate using 5-alphareductase or alphablocants inhibitors may not always be sufficient. A better understanding of the pathophysiology of BPH and its interactions with other drugs will help the development of new substances with a better efficiency. This present work aims to be a modest contribution related to medical treatment in benign prostatic hyperplasia and the role that the generalist practitioner should play in managing of this urinary disease quite common in elderly men.

  11. Chlorella Protein Hydrolysate Attenuates Glucose Metabolic Disorder and Fatty Liver in High-fat Diet-induced Obese Mice.

    Science.gov (United States)

    Noguchi, Naoto; Yanagita, Teruyoshi; Rahman, Shaikh Mizanoor; Ando, Yotaro

    2016-07-01

    Chlorella (Parachlorella beijerinckii) powder is reported to show a preventive effect against metabolic syndromes such as arteriosclerosis, hyperlipidemia, and hypertension. Approximately 60% of the chlorella content is protein. In order to understand the role of chlorella protein, we prepared a chlorella protein hydrolysate (CPH) by protease treatment. Male C57BL/6 mice were divided into three groups: a normal diet group, high-fat diet (HFD) group, and high-fat diet supplemented with CPH (HFD+CPH) group. The CPH administration improved glucose intolerance, insulin sensitivity, and adipose tissue hypertrophy in the high-fat diet-fed mice. In addition, the HFD+CPH group had significantly decreased liver total cholesterol and triglyceride levels compared with those in the HFD group. Furthermore, the HFD+CPH group had a decreased level of monocyte chemotactic protein-1 (MCP-1) in serum and a lower MCP-1 mRNA expression level in adipose tissue compared with the HFD group. The present study suggests that chlorella protein hydrolysate can prevent a high-fat diet-induced glucose disorder and fatty liver by inhibiting adipocyte hypertrophy and reducing the MCP-1 protein and gene expression.

  12. Fat transfer and fatal macroembolization.

    Science.gov (United States)

    Astarita, Denis C; Scheinin, Lisa A; Sathyavagiswaran, Lakshmanan

    2015-03-01

    Fat embolism is usually associated with long bone fractures or other trauma. The diagnosis is usually clinical, and in most cases, emboli are not fatal and not usually seen on gross examination. At the Los Angeles County Coroner's Office, we autopsied the victim of fatal macroscopic fat embolization to the lungs. The patient died during buttock enhancement surgery when fat from liposuction was injected into her buttocks. Fat embolism from liposuction and fat injection is reportedly rare, and macroscopic embolization is rarer still. Varicose veins can occur in the area of the sciatic notch and are known to cause painful sciatica symptoms. We suggest them as a potential conduit for macroscopic fat to reach the lungs. Simple pre-operative questioning for sciatica symptoms and possible radiologic study to rule out sciatic varices seem prudent before undertaking buttock-enhancing surgery. Careful fat injection with pre-aspiration is always advised. © 2015 American Academy of Forensic Sciences.

  13. The relationship of enuresis nocturna and adenoid hypertrophy

    Directory of Open Access Journals (Sweden)

    Muhsin Balaban

    2016-07-01

    Full Text Available Objectives: This study was organized to assess the relationship of enuresis nocturna (EN and upper airway obstruction (UAO in children. Material and Methods: This study was multi-centrically and prospectively designed including 79 children who presented to a urology clinic with symptoms of EN between January 2013 and February 2014. Sixty-four age-matched children with no history of urological complaints were randomly recruited from children admitted to a pediatric clinic as a control group. All children and parents were asked to fill out a dysfunctional elimination syndrome (DES questionnaire and children were examined by an ear, nose and throat (ENT specialist to evaluate the UAO. Descriptive statistics, chisquare and Mann-Whitney-U tests were used to compare variables. Results: The mean ages of the 79 children (48 male, 31 female in the study group and the 64 children (41 male, 23 female in the control group were 10.14+/-3.38 and 9.17+/- 2.85, respectively. Family history of the study showed that 19% of the children’s mothers, 10% of the children’s fathers and 37% of the children’s siblings had experienced EN. There was a significant difference between the study and the control groups in terms of urge to urinate, bladder emptying, bowel symptoms and psychological stress. There was also a significant difference between rates of tonsillar hypertrophy and nasopharynx obstruction in the EN group (p = 0.009. Conclusion: In this study we found that half of the children with EN had tonsillar hypertrophy, which was significantly higher than in the control group. Further studies are needed to clarify the exact relationship between UAO and EN.

  14. Fat Quality Influences the Obesogenic Effect of High Fat Diets

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Cancelliere, Rosa; di Fabio, Giovanni; Zarrelli, Armando; Liverini, Giovanna; Iossa, Susanna

    2015-01-01

    High fat and/or carbohydrate intake are associated with an elevated risk for obesity and chronic diseases such as diabetes and cardiovascular diseases. The harmful effects of a high fat diet could be different, depending on dietary fat quality. In fact, high fat diets rich in unsaturated fatty acids are considered less deleterious for human health than those rich in saturated fat. In our previous studies, we have shown that rats fed a high fat diet developed obesity and exhibited a decrease in oxidative capacity and an increase in oxidative stress in liver mitochondria. To investigate whether polyunsaturated fats could attenuate the above deleterious effects of high fat diets, energy balance and body composition were assessed after two weeks in rats fed isocaloric amounts of a high-fat diet (58.2% by energy) rich either in lard or safflower/linseed oil. Hepatic functionality, plasma parameters, and oxidative status were also measured. The results show that feeding on safflower/linseed oil diet attenuates the obesogenic effect of high fat diets and ameliorates the blood lipid profile. Conversely, hepatic steatosis and mitochondrial oxidative stress appear to be negatively affected by a diet rich in unsaturated fatty acids. PMID:26580650

  15. Fat Quality Influences the Obesogenic Effect of High Fat Diets

    Directory of Open Access Journals (Sweden)

    Raffaella Crescenzo

    2015-11-01

    Full Text Available High fat and/or carbohydrate intake are associated with an elevated risk for obesity and chronic diseases such as diabetes and cardiovascular diseases. The harmful effects of a high fat diet could be different, depending on dietary fat quality. In fact, high fat diets rich in unsaturated fatty acids are considered less deleterious for human health than those rich in saturated fat. In our previous studies, we have shown that rats fed a high fat diet developed obesity and exhibited a decrease in oxidative capacity and an increase in oxidative stress in liver mitochondria. To investigate whether polyunsaturated fats could attenuate the above deleterious effects of high fat diets, energy balance and body composition were assessed after two weeks in rats fed isocaloric amounts of a high-fat diet (58.2% by energy rich either in lard or safflower/linseed oil. Hepatic functionality, plasma parameters, and oxidative status were also measured. The results show that feeding on safflower/linseed oil diet attenuates the obesogenic effect of high fat diets and ameliorates the blood lipid profile. Conversely, hepatic steatosis and mitochondrial oxidative stress appear to be negatively affected by a diet rich in unsaturated fatty acids.

  16. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

  17. Tumor necrosis factor receptor-associated factor 3 is a positive regulator of pathological cardiac hypertrophy.

    Science.gov (United States)

    Jiang, Xi; Deng, Ke-Qiong; Luo, Yuxuan; Jiang, Ding-Sheng; Gao, Lu; Zhang, Xiao-Fei; Zhang, Peng; Zhao, Guang-Nian; Zhu, Xueyong; Li, Hongliang

    2015-08-01

    Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor-related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II- or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3-TBK1-AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process. © 2015 American Heart Association, Inc.

  18. [Preliminary Study of Necroptosis in Cardiac Hypertrophy Induced by Pressure Overload].

    Science.gov (United States)

    Zhao, Mingyue; Qin, Yupei; Lu, Lihui; Tang, Xiaoju; Wu, Wenchao; Fu, Hua; Liu, Xiaojing

    2015-06-01

    The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.

  19. Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy

    Science.gov (United States)

    Cao, Buqing; Yu, Qing; Zhao, Wei; Tang, Zhiping; Cong, Binghai; Du, Jiankui; Lu, Jianqiang; Zhu, Xiaoyan; Ni, Xin

    2016-01-01

    The tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus-mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling. PMID:26823023

  20. Transient receptor potential vanilloid 2 function regulates cardiac hypertrophy via stretch-induced activation.

    Science.gov (United States)

    Koch, Sheryl E; Mann, Adrien; Jones, Shannon; Robbins, Nathan; Alkhattabi, Abdullah; Worley, Mariah C; Gao, Xu; Lasko-Roiniotis, Valerie M; Karani, Rajiv; Fulford, Logan; Jiang, Min; Nieman, Michelle; Lorenz, John N; Rubinstein, Jack

    2017-03-01

    Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps. Wild-type animals served as control for all experiments. Expression and localization of TRPV2 was investigated in wild-type cardiac samples. Changes in cardiac function were measured in vivo via echocardiography and invasive catheterization. Molecular changes, including protein and real-time PCR markers of hypertrophy, were measured in addition to myocyte size. TRPV2 is significantly upregulated in wild-type mice after TAC, though not in response to beta-adrenergic or angiotensin stimulation. TAC-induced stretch stimulus caused an upregulation of TRPV2 in the sarcolemmal membrane. The absence of functional TRPV2 resulted in significantly reduced left ventricular hypertrophy after TAC, though not in response to beta-adrenergic or angiotensin stimulation. The decreased development of hypertrophy was not associated with significant deterioration of cardiac function. We conclude that TRPV2 function, as a stretch-activated channel, regulates the development of cardiomyocyte hypertrophy in response to increased afterload.

  1. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  2. Ubiquitin-specific protease 14 regulates cardiac hypertrophy progression by increasing GSK-3β phosphorylation.

    Science.gov (United States)

    Liu, Ningning; Chai, Renjie; Liu, Bin; Zhang, Zhenhui; Zhang, Shuangwei; Zhang, Jingzhi; Liao, Yuning; Cai, Jianyu; Xia, Xiaohong; Li, Aiqun; Liu, Jinbao; Huang, Hongbiao; Liu, Shiming

    2016-09-23

    Cardiac hypertrophy, a compensatory response to various stimuli in the heart, independently predicts cardiovascular ailments and related deaths. Increasing evidence indicates ubiquitin-proteasome signaling contributes to cardiac hypertrophy regulation. Here, we identified ubiquitin-specific protease 14 (USP14), a 19S proteasome associated deubiquitinase (DUB), as a novel target for cardiac hypertrophy therapy via inhibition of the GSK-3β pathway. Indeed, USP14 expression was increased in an animal model of abdominal aorta constriction. In an angiotensin II (AngII) induced primary neonatal rat cardiomyocyte hypertrophy model, USP14 expression was increased in a time-dependent manner, and reduced USP14 deubiquitinase activity or USP14 knockdown resulted in lower expression levels of the myocardial hypertrophy specific marker β-MHC, and subsequent decreased GSK-3β phosphorylation. In conclusion, USP14 mediates the development of cardiac hypertrophy by promoting GSK-3β phosphorylation, suggesting that USP14 might represent a novel therapeutic target for cardiac hypertrophy treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ai-Lan [Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Ou, Cai-Wen [The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); He, Zhao-Chu [Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Liu, Qi-Cai [Experimental Medical Research Center, Guangzhou Medical University, Guangzhou (China); Dong, Qi [Department of Physiology, Guangzhou Medical University, Guangzhou (China); Chen, Min-Sheng [Guangzhou Key Laboratory of Cardiovascular Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China)

    2012-10-15

    Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [{sup 3}H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

  4. Calcium Signaling Regulates Ventricular Hypertrophy During Development Independent of Contraction or Blood Flow

    Science.gov (United States)

    Andersen, Nicholas D.; Ramachandran, Kapil V.; Bao, Michelle M.; Kirby, Margaret L.; Pitt, Geoffrey S.; Hutson, Mary R.

    2014-01-01

    In utero interventions aimed at restoring left ventricular hemodynamic forces in fetuses with prenatally diagnosed hypoplastic left heart syndrome failed to stimulate ventricular myocardial growth during gestation, suggesting chamber growth during development may not rely upon fluid forces. We therefore hypothesized that ventricular hypertrophy during development may depend upon fundamental Ca2+-dependent growth pathways that function independent of hemodynamic forces. To test this hypothesis, zebrafish embryos were treated with inhibitors or activators of Ca2+ signaling in the presence or absence of contraction during the period of chamber development. Abolishment of contractile function alone in the setting of preserved Ca2+ signaling did not impair ventricular hypertrophy. In contrast, inhibition of L-type voltage-gated Ca2+ influx abolished contraction and led to reduced ventricular hypertrophy, whereas increasing L-type voltage-gated Ca2+ influx led to enhanced ventricular hypertrophy in either the presence or absence of contraction. Similarly, inhibition of the downstream Ca2+-sensitive phosphatase calcineurin, a known regulator of adult cardiac hypertrophy, led to reduced ventricular hypertrophy in the presence or absence of contraction, whereas hypertrophy was rescued in the absence of L-type voltage-gated Ca2+ influx and contraction by expression of a constitutively active calcineurin. These data suggest ventricular cardiomyocyte hypertrophy during chamber formation is dependent upon Ca2+ signaling pathways that are unaffected by heart function or hemodynamic forces. Disruption of Ca2+-dependent hypertrophy during heart development may therefore represent one mechanism for impaired chamber formation that is not related to impaired blood flow. PMID:25536179

  5. MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy.

    Directory of Open Access Journals (Sweden)

    Wei Pan

    Full Text Available Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (operation group. Cardiomyocyte autophagy was enhanced in rats from the operation group, compared with those in the sham operation group. Moreover, the operation group showed up-regulation of beclin-1 (an autophagy-related gene, and down-regulation of miR-30 in cardiac tissue. The effects of inhibition and over-expression of the beclin-1 gene on the expression of hypertrophy-related genes and on autophagy were assessed. Angiotensin II-induced myocardial hypertrophy was found to be mediated by over-expression of the beclin-1 gene. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. miR-30a induced alterations in beclin-1 gene expression and autophagy in cardiomyocytes. Treatment of cardiomyocytes with miR-30a mimic attenuated the Angiotensin II-induced up-regulation of hypertrophy-related genes and decreased in the cardiomyocyte surface area. Conversely, treatment with miR-30a inhibitor enhanced the up-regulation of hypertrophy-related genes and increased the surface area of cardiomyocytes induced by Angiotensin II. In addition, circulating miR-30 was elevated in patients with left ventricular hypertrophy, and circulating miR-30 was positively associated with left ventricular wall thickness. Collectively, these above-mentioned results suggest that Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. Circulating miR-30 may be an important marker for the diagnosis of left ventricular hypertrophy.

  6. Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload.

    Science.gov (United States)

    Li, Wei-Ming; Zhao, Yi-Fan; Zhu, Guo-Fu; Peng, Wen-Hui; Zhu, Meng-Yun; Yu, Xue-Jing; Chen, Wei; Xu, Da-Chun; Xu, Ya-Wei

    2017-01-01

    Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy. © 2016 The

  7. Body fat, abdominal fat and body fat distribution related to VO(2PEAK) in young children

    DEFF Research Database (Denmark)

    Dencker, Magnus; Wollmer, Per; Karlsson, Magnus K

    2011-01-01

    Abstract Objective. Aerobic fitness, defined as maximum oxygen uptake (VO(2PEAK)), and body fat measurements represent two known risk factors for disease. The purpose of this study was to investigate the relationship between VO(2PEAK) and body fat measurements in young children at a population......-based level. Methods. Cross-sectional study of 225 children (128 boys and 97 girls) aged 8-11 years, recruited from a population-based cohort. Total lean body mass (LBM), total fat mass (TBF), and abdominal fat mass (AFM) were measured by dual-energy x-ray absorptiometry. Body fat was also calculated...... as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Results. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute...

  8. Left atrial systolic force in hypertensive patients with left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Chinali, M.; Simone, G. de; Wachtell, K.

    2008-01-01

    with larger left ventricular diameter and higher left ventricular mass index (both P hypertrophy was greater (84 vs. 64%; P cardiac output......In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial......, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P hypertrophy, but normal left ventricular chamber systolic function with increased...

  9. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, M; Vissing, J

    2013-01-01

    , and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest......Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic...

  10. Ethanolic Extract of Taheebo Attenuates Increase in Body Weight and Fatty Liver in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Won Hee Choi

    2014-10-01

    Full Text Available We evaluated whether intake of an ethanolic extract of Taheebo (TBE from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w for 11 weeks. The diet of control (HFD mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage; the diet of experimental (TBE mice was supplemented with TBE (150 mg/kg body weight/day by gavage. Mice administered TBE had significantly reduced body weight gain, fat accumulation in the liver, and fat pad weight, compared to HFD mice. Reduced hypertrophy of fat cells was also observed in TBE mice. Mice administered TBE also showed significantly lower serum levels of triglycerides, insulin, and leptin. Lipid profiles and levels of mRNAs and proteins related to lipid metabolism were determined in liver and white adipose tissue of the mice. Expression of mRNA and proteins related to lipogenesis were decreased in TBE-administered mice compared to mice fed HFD alone. These results suggest that TBE inhibits obesity and fat accumulation by regulation of gene expression related to lipid metabolism in HFD-induced obesity in mice.

  11. Facial Fat Necrosis Following Autologous Fat Transfer and its Management

    OpenAIRE

    Sweta Rai; Alexander M Marsland; Vishal Madan

    2014-01-01

    Autologous fat transfer (AFT) is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the...

  12. Facial fat necrosis following autologous fat transfer and its management

    Directory of Open Access Journals (Sweden)

    Sweta Rai

    2014-01-01

    Full Text Available Autologous fat transfer (AFT is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the benefits and risks of AFT highlighting common causes of fat graft failure.

  13. Fat circadian biology.

    Science.gov (United States)

    Gimble, Jeffrey M; Floyd, Z Elizabeth

    2009-11-01

    While adipose tissue has long been recognized for its major role in metabolism, it is now appreciated as an endocrine organ. A growing body of literature has emerged that identifies circadian mechanisms as a critical regulator of adipose tissue differentiation, metabolism, and adipokine secretory function in both health and disease. This concise review focuses on recent data from murine and human models that highlights the interplay between the core circadian regulatory proteins and adipose tissue in the context of energy, fat, and glucose metabolism. It will be important to integrate circadian mechanisms and networks into future descriptions of adipose tissue physiology.

  14. Fat sensing and metabolic syndrome.

    Science.gov (United States)

    Youn, Jang H

    2014-12-01

    Overconsumption of dietary fat contributes to the development of obesity and metabolic syndrome. Recent evidence suggests that high dietary fat may promote these metabolic states not only by providing calories but also by inducing impaired control of energy balance. In normal metabolic states, fat interacts with various organs or receptors to generate signals for the regulation of energy balance. Many of these interactions are impaired by high-fat diets or in obesity, contributing to the development or maintenance of obesity. These impairments may arise largely from fundamental alterations in the hypothalamus where all peripheral signals are integrated to regulate energy balance. This review focuses on various mechanisms by which fat is sensed at different stages of ingestion, circulation, storage, and utilization to regulate food intake, and how these individual mechanisms are altered by high-fat diets or in obesity.

  15. Cardiac-specific ablation of glutaredoxin 3 leads to cardiac hypertrophy and heart failure

    Science.gov (United States)

    Experimental and clinical investigations have demonstrated that reactive oxygen species (ROS) production is increased during cardiac hypertrophy and heart failure. Excess ROS can directly impair cardiac contraction through modification of Ca2+ handling proteins or activate multiple effectors and sig...

  16. Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography

    DEFF Research Database (Denmark)

    Sandager Petersen, Søren; Reinholdt Pedersen, Line; Pareek, Manan

    2017-01-01

    OBJECTIVE: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. METHODS: We tested cross-sectional associations ...

  17. Isolated papillary muscle hypertrophy: A gap in our knowledge of hypertrophic cardiomyopathy?

    Science.gov (United States)

    Ferreira, Catarina; Delgado, Carlos; Vázquez, María; Trinidad, Carmen; Vilar, Manuel

    2014-06-01

    Increased thickness of left ventricular walls is the predominant characteristic and one of the diagnostic criteria of hypertrophic cardiomyopathy (HCM). This case illustrates an uncommon but important finding of isolated hypertrophy of the papillary muscles (PMs), observed in a young woman in whom an abnormal electrocardiogram was initially detected. During the investigation isolated PM hypertrophy was identified. The structural characteristics of the PMs have received scant attention in this setting and there is little information in the literature on this entity, whose real prevalence and clinical significance remain to be determined. The available information relates solitary PM hypertrophy with an early form or a different pattern of HCM. In this case PM hypertrophy was only detected due to the finding of an abnormal electrocardiogram, which prompted further diagnostic tests and a search for possible etiologies. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  18. Impact of fasting glucose on electrocardiographic left ventricular hypertrophy in an elderly general population

    DEFF Research Database (Denmark)

    Diederichsen, Søren Z; Pareek, Manan; Nielsen, Mette L

    2015-01-01

    OBJECTIVE: To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. METHODS: Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH...

  19. Repression of Cardiac Hypertrophy by KLF15: Underlying Mechanisms and Therapeutic Implications

    NARCIS (Netherlands)

    Leenders, Joost J.; Wijnen, Wino J.; van der Made, Ingeborg; Hiller, Monika; Swinnen, Melissa; VandenDriessche, Thierry; Chuah, Marinee; Pinto, Yigal M.; Creemers, Esther E.

    2012-01-01

    The Kruppel-like factor (KLF) family of transcription factors regulates diverse cell biological processes including proliferation, differentiation, survival and growth. Previous studies have shown that KLF15 inhibits cardiac hypertrophy by repressing the activity of pivotal cardiac transcription

  20. Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); J.M. van Gool (Jeanette); M.J.M. Kofflard (Marcel); A.H.J. Danser (Jan); F.J. ten Cate (Folkert)

    2001-01-01

    textabstractThe development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1

  1. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

    NARCIS (Netherlands)

    Zhong, Leilei; Huang, X; Karperien, Hermanus Bernardus Johannes; Post, Janine Nicole

    2015-01-01

    Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the

  2. [Body fat distribution: anthropometric indicators].

    Science.gov (United States)

    Yáñez, M; Albala, C

    1995-12-01

    There are two types of fat distribution in obese subjects. The abdominal, superior, android or apple shaped and the gluteo-femoral, gynecoid, inferior or pear shaped. In the former, fat is accumulated in the abdomen and in the latter, in the gluteal region. The superior distribution is associated with a higher risk of cardiovascular diseases. Among anthropometric measurements of fat distribution, the ratio between waist circumference measured at the level of the navel and hip circumference, measured at the level of greater trochanters, is the best indicator. Using the cutoff points of 0.8 for women and 1 for men, it has a good correlation with visceral fat.

  3. SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    Tang, Xiaoqiang; Chen, Xiao-Feng; Wang, Nan-Yu; Wang, Xiao-Man; Liang, Shu-Ting; Zheng, Wei; Lu, Yun-Biao; Zhao, Xiang; Hao, De-Long; Zhang, Zhu-Qin; Zou, Ming-Hui; Liu, De-Pei; Chen, Hou-Zao

    2017-11-21

    Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy. Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic ( SIRT2 -Tg) mice, and their respective littermates (8 to ≈12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice. Sirt2 knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II-infused mice. Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II-induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy

  4. Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M

    2010-01-01

    We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH).......We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH)....

  5. Asymmetric septal hypertrophy - a marker of hypertension in aortic stenosis (a SEAS substudy)

    DEFF Research Database (Denmark)

    Tuseth, Nora; Cramariuc, Dana; Rieck, Ashild E

    2010-01-01

    Some patients with aortic stenosis develop asymmetric septal hypertrophy (ASH) that may influence the surgical approach and is associated with higher perioperative morbidity. The aim of this analysis was to characterize further this subtype of aortic stenosis patients.......Some patients with aortic stenosis develop asymmetric septal hypertrophy (ASH) that may influence the surgical approach and is associated with higher perioperative morbidity. The aim of this analysis was to characterize further this subtype of aortic stenosis patients....

  6. Atopy does not affect the frequency of adenotonsillar hypertrophy and sleep apnoea in children who snore.

    Science.gov (United States)

    Alexopoulos, Emmanouel I; Bizakis, John; Gourgoulianis, Konstantinos; Kaditis, Athanasios G

    2014-12-01

    Viral respiratory infections and atopy have been implicated in the pathogenesis of adenotonsillar hypertrophy and obstructive sleep apnoea (OSA), but the role of atopy is controversial. We aimed to test our hypothesis that atopy, expressed as physician-diagnosed eczema, was associated with adenotonsillar hypertrophy and OSA among children who snored. Data on children who snored and were referred for polysomnography were reviewed. The primary outcome measures were adenotonsillar hypertrophy and OSA. We analysed data on 855 children with a mean age (±standard deviation) of 6.3 (±2.5) years and median obstructive apnoea-hypopnea index of 2.1 episodes per hour. Of the 855 subjects, 133 (15.6%) had physician-diagnosed eczema, 591 (69.1%) had adenoidal hypertrophy, 605 (70.8%) had tonsillar hypertrophy, 219 (25.6%) were obese and 470 (55%) had OSA. Eczema was not related to adenoidal or tonsillar hypertrophy after adjustment for gender and age, with odds ratios (OR) of 1.00 (95% confidence interval 0.67-1.49; p = 0.98) and 0.88 (95% confidence interval 0.59-1.32; p = 0.54), respectively. Similarly, eczema did not affect OSA frequency after adjustment for adenoidal and tonsillar hypertrophy, obesity, gender and age, with an adjusted OR of 0.82 (0.56-1.21; p = 0.32). Atopy was not related to adenotonsillar hypertrophy or OSA in children who snore. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  7. UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein accumulation.

    Science.gov (United States)

    Lohmann, Frithjof; Sachs, Marlies; Meyer, Tobias N; Sievert, Henning; Lindenmeyer, Maja T; Wiech, Thorsten; Cohen, Clemens D; Balabanov, Stefan; Stahl, R A K; Meyer-Schwesinger, Catherine

    2014-07-01

    Podocytes are terminally differentiated cells of the glomerular filtration barrier that react with hypertrophy in the course of injury such as in membranous nephropathy (MGN). The neuronal deubiquitinase ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed and activated in podocytes of human and rodent MGN. UCH-L1 regulates the mono-ubiquitin pool and induces accumulation of poly-ubiquitinated proteins in affected podocytes. Here, we investigated the role of UCH-L1 in podocyte hypertrophy and in the homeostasis of the hypertrophy associated "model protein" p27(Kip1). A better understanding of the basic mechanisms leading to podocyte hypertrophy is crucial for the development of specific therapies in MGN. In human and rat MGN, hypertrophic podocytes exhibited a simultaneous up-regulation of UCH-L1 and of cytoplasmic p27(Kip1) content. Functionally, inhibition of UCH-L1 activity and knockdown or inhibition of UCH-L1 attenuated podocyte hypertrophy by decreasing the total protein content in isolated glomeruli and in cultured podocytes. In contrast, UCH-L1 levels and activity increased podocyte hypertrophy and total protein content in culture, specifically of cytoplasmic p27(Kip1). UCH-L1 enhanced cytoplasmic p27(Kip1) levels by nuclear export and decreased poly-ubiquitination and proteasomal degradation of p27(Kip1). In parallel, UCH-L1 increased podocyte turnover, migration and cytoskeletal rearrangement, which are associated with known oncogenic functions of cytoplasmic p27(Kip1) in cancer. We propose that UCH-L1 induces podocyte hypertrophy in MGN by increasing the total protein content through altered degradation and accumulation of proteins such as p27(Kip1) in the cytoplasm of podocytes. Modification of both UCH-L1 activity and levels could be a new therapeutic avenue to podocyte hypertrophy in MGN. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Health-related quality of life among children with adenoid hypertrophy in Xi'an, China.

    Science.gov (United States)

    Jiang, Xun; Ren, Xiaoyong; Liu, Haiqin; Tian, Jiao; Du, Chunyan; Luo, Huanan; Cheng, Ying; Shang, Lei

    2015-12-01

    The aim of this study was to investigate the health-related quality of life (HRQOL) in 5-7-year-old children diagnosed with adenoid hypertrophy and the impact of adenoid hypertrophy on affected families. This is a cross-sectional case-control study evaluating 5-7-year-old children with adenoid hypertrophy (n=195), 5-7-year-old healthy children (n=156), and associated caregivers (parents and/or grandparents). A Chinese version of the PedsQL™ 4.0 Generic Core Scale was used to assess childhood HRQOL, and a Chinese version of the Family Impact Module (FIM) was used to assess the impact of adenoid hypertrophy on family members. HRQOL scores were compared between the children with adenoid hypertrophy and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, and caregiver's HRQOL as independent variables were referenced to determine the factors that may influence HRQOL in children with adenoid hypertrophy. Children with adenoid hypertrophy showed significantly lower physical, emotional, social, and school functioning scores than healthy children (phypertrophy also scored significantly lower than caregivers for healthy children on physical, emotional, social, cognitive, and communication functioning (phypertrophy-affected children also exhibited significantly higher levels of worry than healthy children (phypertrophy (phypertrophy were associated with lower HRQOL in both children and their caregivers, and may negatively influence family functioning. In addition, caregivers' social characteristics may also significantly affect the HRQOL in children with adenoid hypertrophy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Whey protein hydrolysate augments tendon and muscle hypertrophy independent of resistance exercise contraction mode

    DEFF Research Database (Denmark)

    Farup, Jean; Rahbek, S K; Vendelbo, M H

    2014-01-01

    In a comparative study, we investigated the effects of maximal eccentric or concentric resistance training combined with whey protein or placebo on muscle and tendon hypertrophy. 22 subjects were allocated into either a high-leucine whey protein hydrolysate + carbohydrate group (WHD...... or contraction mode effects. In conclusion, high-leucine whey protein hydrolysate augments muscle and tendon hypertrophy following 12 weeks of resistance training – irrespective of contraction mode....

  10. Compromised Myocardial Energetics in Hypertrophied Mouse Hearts Diminish the Beneficial Effect of Overexpressing SERCA2a

    OpenAIRE

    Pinz, Ilka; Tian, Rong; Belke, Darrell; Swanson, Eric; Dillmann, Wolfgang; Ingwall, Joanne S.

    2011-01-01

    The sarcoplasmic reticulum calcium ATPase (SERCA) plays a central role in regulating intracellular Ca2+ homeostasis and myocardial contractility. Several studies show that improving Ca2+ handling in hypertrophied rodent hearts by increasing SERCA activity results in enhanced contractile function. This suggests that SERCA is a potential target for gene therapy in cardiac hypertrophy and failure. However, it raises the issue of increased energy cost resulting from a higher ATPase activity. In t...

  11. Calhex₂₃₁ Ameliorates Cardiac Hypertrophy by Inhibiting Cellular Autophagy in Vivo and in Vitro.

    Science.gov (United States)

    Liu, Lei; Wang, Chao; Sun, Dianjun; Jiang, Shuangquan; Li, Hong; Zhang, Weihua; Zhao, Yajun; Xi, Yuhui; Shi, Sa; Lu, Fanghao; Tian, Ye; Xu, Changqing; Wang, Lina

    2015-01-01

    Intracellular calcium concentration ([Ca2+]i) homeostasis, an initial factor of cardiac hypertrophy, is regulated by the calcium-sensing receptor (CaSR) and is associated with the formation of autolysosomes. The aim of this study was to investigate the role of Calhex231, a CaSR inhibitor, on the hypertrophic response via autophagy modulation. Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in 40 male Wistar rats, while 10 rats underwent a sham operation and served as controls. Cardiac function was monitored by transthoracic echocardiography, and the hypertrophy index was calculated. Cardiac tissue was stained with hematoxylin and eosin (H&E) or Masson’s trichrome reagent and examined by transmission electron microscopy. An angiotensin II (Ang II)-induced cardiomyocyte hypertrophy model was established and used to test the involvement of active molecules. Intracellular calcium concentration ([Ca2+]i) was determined by the introduction of Fluo-4/AM dye followed by confocal microscopy. The expression of various active proteins was analyzed by western blot. The rats with TAC-induced hypertrophy had an increased heart size, ratio of heart weight to body weight, myocardial fibrosis, and CaSR and autophagy levels, which were suppressed by Calhex231. Experimental results using Ang II-induced hypertrophic cardiomyocytes confirmed that Calhex231 suppressed CaSR expression and downregulated autophagy by inhibiting the Ca2+/calmodulin-dependent-protein kinase-kinase-β (CaMKKβ)– AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway to ameliorate cardiomyocyte hypertrophy. Calhex231 ameliorates myocardial hypertrophy induced by pressure-overload or Ang II via inhibiting CaSR expression and autophagy. Our results may support the notion that Calhex231 can become a new therapeutic agent for the treatment of cardiac hypertrophy. © 2015 S. Karger AG, Basel.

  12. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C

    1993-01-01

    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients...... with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility....

  13. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

    2013-07-15

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

  14. MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor.

    Science.gov (United States)

    Bao, Qinxue; Zhao, Mingyue; Chen, Li; Wang, Yu; Wu, Siyuan; Wu, Wenchao; Liu, Xiaojing

    2017-04-15

    Sigma-1 receptor (Sig-1R) is a ligand-regulated endoplasmic reticulum (ER) chaperone involved in cardiac hypertrophy, but it is not known whether Sig-1R is regulated by microRNAs (miRNAs). According to bioinformatic analysis, miR-297 was suggested as a potential target miRNA for Sig-1R. Therefore, we verified whether miR-297 could target Sig-1R and investigated the possible mechanisms underlying the role of miR-297 in cardiac hypertrophy. Bioinformatic analysis combined with laboratory experiments, including quantitative RT-PCR, Western blotting, and luciferase assay, were performed to identify the target miRNA of Sig-1R. Transverse aortic constriction (TAC) model and neonatal rat cardiomyocytes (NCMs) stimulated with angiotensin II (AngII) were used to explore the relationship between miR-297 and Sig-1R. Additionally, the function of miR-297 in cardiomyocyte hypertrophy and ER stress/unfolded protein response (UPR) signaling pathway was investigated by transfecting miR-297 mimics/inhibitor. miR-297 levels were increased in both TAC-induced hypertrophic heart tissue and AngII-induced cardiomyocyte hypertrophy. Up-regulation of miR-297 by specific mimics exacerbated AngII-induced cardiomyocyte hypertrophy, whereas inhibition of miR-297 suppressed the process. During cardiomyocyte hypertrophy, Sig-1R expression, which was negatively regulated by miR-297 by directly targeting its 3'untranslated region (UTR), was decreased. Furthermore, attenuation of miR-297 inhibited the activation of X-box binding protein 1 (Xbp1) and activating transcriptional factor 4 (ATF4) signaling pathways in NCMs. Our data demonstrate that miR-297 promotes cardiomyocyte hypertrophy by inhibiting the expression of Sig-1R and activation of ER stress signaling, which provides a novel interpretation for cardiac hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy.

    Science.gov (United States)

    Wu, Q-Q; Zong, J; Gao, L; Dai, J; Yang, Z; Xu, M; Fang, Y; Ma, Z-G; Tang, Q-Z

    2014-05-01

    Cardiac hypertrophy is an adaptive process of the heart in response to various stimuli, but sustained cardiac hypertrophy will finally lead to heart failure. Sulforaphane-extracted from cruciferous vegetables of the genus Brassica such as broccoli, brussels sprouts, and cabbage-has been evaluated for its anticarcinogenic and antioxidant effects. To investigate the effect of sulforaphane on angiotensin II (Ang II)-induced cardiac hypertrophy in vitro. Embryonic rat heart-derived H9c2 cells were co-incubated with sulforaphane and Ang II. The cell surface area and mRNA levels of hypertrophic markers were measured to clarify the effect of sulforaphane on cardiac hypertrophy. The underlying mechanism was further investigated by detecting the activation of Akt and NF-κB signaling pathways. We found that H9c2 cells pretreated with sulforaphane were protected from Ang II-induced hypertrophy. The increasing mRNA levels of ANP, BNP, and β-MHC in Ang II-stimulated cells were also down-regulated after sulforaphane treatment. Moreover, sulforaphane repressed the Ang II-induced phosphorylation of Akt, GSK3β, mTOR, eIF4e, as well as of IκBα and NF-κB. Based on our results, sulforaphane attenuates Ang II-induced hypertrophy of H9c2 cardiomyocytes mediated by the inhibition of intracellular signaling pathways including Akt and NF-κB.

  16. The prevelance of psichiatric symptoms in preschool children with adenotonsillar hypertrophy.

    Science.gov (United States)

    Soylu, Erkan; Soylu, Nusret; Yıldırım, Yavuz Selim; Polat, Cahit; Sakallıoğlu, Oner

    2013-07-01

    The aim of this study was to determine the prevalence of psychiatric disorders and symptoms in preschool-age children who are indicated for operation due to adenotonsillar hypertrophy. Forty-eight patients between the ages of three and five years with indication for adenotonsillectomy were included in the study, as well as 40 control patients. Cases underwent routine ear nose throat (ENT) examination, flexible nasopharyngoscopy and tympanometry. The Early Childhood Inventory-4 (ECI-4) parent form and Strengths and Difficulties Questionnaire (SDQ) parent form were completed by the parent caring for the child. The SPSS for Windows 16.0 program was used for statistical analysis. Groups were compared according to they received at least one psychiatric diagnosis measured by ECI-4, the group of adenotonsillar hypertrophy was diagnosed more than the control group. Attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and sleep disorders were detected at a higher rate in patients with adenotonsillar hypertrophy. It also was established that in the comparison of the severity of psychiatric symptoms determined by ECI-4, symptom severity of ADHD, ODD, anxiety disorders, and sleep disorders was higher in the adenotonsillar hypertrophy group than in the control group. In the evaluation of the SDQ parent form, it was determined that attention deficit, hyperactivity, behavioral, and peer relations problems occurred more frequently in the adenotonsillar hypertrophy group. In addition to oral respiration, snoring, and disordered breathing during sleep, adenotonsillar hypertrophy may also associated with psychiatric disorders and symptoms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Telmisartan suppresses cardiac hypertrophy by inhibiting cardiomyocyte apoptosis via the NFAT/ANP/BNP signaling pathway.

    Science.gov (United States)

    Li, Xiurong; Lan, Yuhuai; Wang, Yan; Nie, Minghao; Lu, Yanhong; Zhao, Eryang

    2017-05-01

    Telmisartan, a type of angiotensin II (Ang II) receptor inhibitor, is a common agent used to treat hypertension in the clinic. Hypertension increases cardiac afterload and promotes cardiac hypertrophy. However, the ventricular Ang II receptor may be activated in the absence of hypertension. Therefore, telmisartan may reduce cardiac hypertrophy by indirectly ameliorating hypertensive symptoms and directly inhibiting the cardiac Ang II receptor. Nuclear factor of activated T‑cells (NFAT) contributes to cardiac hypertrophy via nuclear translocation, which induces a cascade of atrial natriuretic peptide (ANP) and brain/B‑type natriuretic peptide (BNP) expression and cardiomyocyte apoptosis. However, NFAT-mediated inhibition of cardiac hypertrophy by telmisartan remains poorly understood. The present study demonstrated that telmisartan suppressed cardiomyocyte hypertrophy in a mouse model of cardiac afterload and in cultured cardiomyocytes by inhibiting NFAT nuclear translocation, as well as by inhibiting ANP and BNP expression and cardiomyocyte apoptosis, in a dose‑dependent manner. The present study provides a novel insight into the potential underlying mechanisms of telmisartan-induced inhibition of cardiomyocyte hypertrophy, which involves inhibition of NFAT activation, nuclear translocation and the ANP/BNP cascade.

  18. Systematic review of the synergist muscle ablation model for compensatory hypertrophy.

    Science.gov (United States)

    Terena, Stella Maris Lins; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalill; Deana, Alessandro Melo; Mesquita-Ferrari, Raquel Agnelli

    2017-02-01

    The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. This model differs from other overload models (exercise and training) regarding the characteristics involved in the hypertrophy process (acute) and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

  19. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

    Science.gov (United States)

    White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

    2014-11-04

    Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

  20. Adenotonsillar hypertrophy as a risk factor of dentofacial abnormality in Korean children.

    Science.gov (United States)

    Kim, Dong-Kyu; Rhee, Chae Seo; Yun, Pil-Young; Kim, Jeong-Whun

    2015-11-01

    No studies for the role of adenotonsillar hypertrophy in development of dentofacial abnormalities have been performed in Asian pediatric population. Thus, we aimed to investigate the relationship between adenotonsillar hypertrophy and dentofacial abnormalities in Korean children. The present study included consecutive children who visited a pediatric clinic for sleep-disordered breathing due to habitual mouth breathing, snoring or sleep apnea. Their palatine tonsils and adenoids were graded by oropharyngeal endoscopy and lateral cephalometry. Anterior open bite, posterior crossbite, and Angle's class malocclusions were evaluated for dentofacial abnormality. The receiver-operating characteristic curve analysis was used to identify age cutoffs to predict dentofacial abnormality. A total of 1,083 children were included. The presence of adenotonsillar hypertrophy was significantly correlated with the prevalence of dentofacial abnormality [adjusted odds ratio = 4.587, 95% CI (2.747-7.658)] after adjusting age, sex, body mass index, allergy, and Korean version of obstructive sleep apnea-18 score. The cutoff age associated with dentofacial abnormality was 5.5 years (sensitivity = 75.5%, specificity = 67%) in the children with adenotonsillar hypertrophy and 6.5 years (sensitivity = 70.6%, specificity = 57%) in those without adenotonsillar hypertrophy. In conclusion, adenotonsillar hypertrophy may be a risk factor for dentofacial abnormalities in Korean children and early surgical intervention could be considered with regards to dentofacial abnormality.

  1. Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

    Science.gov (United States)

    Xie, Jun; He, Guixin; Chen, Qinhua; Sun, Jiayin; Dai, Qin; Lu, Jianrong; Li, Guannan; Wu, Han; Li, Ran; Chen, Jianzhou; Xu, Wei; Xu, Biao

    2016-01-01

    Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4–/–) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4–/– compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID:26835698

  2. The alpha1-adrenergic receptors in cardiac hypertrophy: signaling mechanisms and functional implications.

    Science.gov (United States)

    Cotecchia, Susanna; Del Vescovo, Cosmo Damiano; Colella, Matilde; Caso, Stefania; Diviani, Dario

    2015-10-01

    Cardiac hypertrophy is a complex remodeling process of the heart induced by physiological or pathological stimuli resulting in increased cardiomyocyte size and myocardial mass. Whereas cardiac hypertrophy can be an adaptive mechanism to stressful conditions of the heart, prolonged hypertrophy can lead to heart failure which represents the primary cause of human morbidity and mortality. Among G protein-coupled receptors, the α1-adrenergic receptors (α1-ARs) play an important role in the development of cardiac hypertrophy as demonstrated by numerous studies in the past decades, both in primary cardiomyocyte cultures and genetically modified mice. The results of these studies have provided evidence of a large variety of α1-AR-induced signaling events contributing to the defining molecular and cellular features of cardiac hypertrophy. Recently, novel signaling mechanisms have been identified and new hypotheses have emerged concerning the functional role of the α1-adrenergic receptors in the heart. This review will summarize the main signaling pathways activated by the α1-AR in the heart and their functional implications in cardiac hypertrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy.

    Science.gov (United States)

    Wang, Zhihua; Zhang, Xiao-Jing; Ji, Yan-Xiao; Zhang, Peng; Deng, Ke-Qiong; Gong, Jun; Ren, Shuxun; Wang, Xinghua; Chen, Iris; Wang, He; Gao, Chen; Yokota, Tomohiro; Ang, Yen Sin; Li, Shen; Cass, Ashley; Vondriska, Thomas M; Li, Guangping; Deb, Arjun; Srivastava, Deepak; Yang, Huang-Tian; Xiao, Xinshu; Li, Hongliang; Wang, Yibin

    2016-10-01

    Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we identified a heart-enriched long noncoding (lnc)RNA, named cardiac-hypertrophy-associated epigenetic regulator (Chaer), which is necessary for the development of cardiac hypertrophy. Mechanistically, Chaer directly interacts with the catalytic subunit of polycomb repressor complex 2 (PRC2). This interaction, which is mediated by a 66-mer motif in Chaer, interferes with PRC2 targeting to genomic loci, thereby inhibiting histone H3 lysine 27 methylation at the promoter regions of genes involved in cardiac hypertrophy. The interaction between Chaer and PRC2 is transiently induced after hormone or stress stimulation in a process involving mammalian target of rapamycin complex 1, and this interaction is a prerequisite for epigenetic reprogramming and induction of genes involved in hypertrophy. Inhibition of Chaer expression in the heart before, but not after, the onset of pressure overload substantially attenuates cardiac hypertrophy and dysfunction. Our study reveals that stress-induced pathological gene activation in the heart requires a previously uncharacterized lncRNA-dependent epigenetic checkpoint.

  4. Overexpression of mitofilin in the mouse heart promotes cardiac hypertrophy in response to hypertrophic stimuli.

    Science.gov (United States)

    Zhang, Yuan; Xu, Jing; Luo, Yu-Xuan; An, Xi-Zhou; Zhang, Ran; Liu, Guang; Li, Hongliang; Chen, Hou-Zao; Liu, De-Pei

    2014-10-20

    Mitofilin was originally described as a heart muscle protein because of its abundance in the heart tissue; however, its function in the heart is still to be elucidated. Thus, this study aims at investigating the role of mitofilin in the heart in response to hypertrophic stimuli. In this study, a significant increase in mitofilin expression was observed in the hearts of patients with hypertrophic cardiomyopathy. Transgenic (TG) mice with cardiomyocyte-specific overexpression of mitofilin were generated, and cardiac hypertrophy was introduced by transverse aortic constriction (TAC) or chronic infusion of isoproterenol (ISO). In TG mice overexpressing mitofilin, the level of cardiac hypertrophy was significantly greater than that in wild-type (WT) mice after TAC and ISO stimulation. A detailed analysis showed that compared with WT mice, the level of reactive oxygen species was increased after TAC and ISO induction and mitochondrial oxidative phosphorylation (OXPHOS) activity in the TG hearts was lower. These alterations may contribute to the aggravated cardiac hypertrophy observed in response to TAC and ISO stimulation. Over-expression of mitofilin promotes cardiac hypertrophy under pathological conditions both in vivo and in vitro. Mitofilin, a mitochondria protein, is shown to be related to cardiac hypertrophy for the first time, which enhances our understanding of the role of mitochondria in cardiac hypertrophy.

  5. SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle.

    Science.gov (United States)

    Koltai, Erika; Bori, Zoltán; Chabert, Clovis; Dubouchaud, Hervé; Naito, Hisashi; Machida, Shuichi; Davies, Kelvin Ja; Murlasits, Zsolt; Fry, Andrew C; Boldogh, Istvan; Radak, Zsolt

    2017-06-01

    Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  6. The role of the actinomyces in obstructive tonsillar hypertrophy and recurrent tonsillitis in pediatric population.

    Science.gov (United States)

    Kutluhan, Ahmet; Salvız, Mehti; Yalçıner, Gökhan; Kandemir, Olcay; Yeşil, Cemile

    2011-03-01

    To determine the prevalence of tonsillar Actinomyces in subjects with recurrent tonsillitis and those with obstructive tonsillar hypertrophy, and to determine the association between the presence of Actinomyces and tonsillar volume, and crypt abscess. A prospective designed cross-sectional study consisted of 90 children subjects who underwent tonsillectomy or adenotonsillectomy for recurrent tonsillitis and obstructive tonsillar hypertrophy. The subjects of recurrent tonsillitis (Group A) and obstructive tonsillar hypertrophy (Group B) were compared to the presence of Actinomyces. The relationship between the presence of Actinomyces and the presence of crypt abscess, and tonsillar volume were also compared. Actinomyces was found to be significantly more prominent in obstructive tonsillar hypertrophy group (61.5%) compared to recurrent tonsillitis group (26.6%) (pActinomyces than those without (pActinomyces. According to the presented study, Actinomyces was seen more prominent in subjects with obstructive tonsillar hypertrophy compared those with recurrent tonsillitis. Furthermore Actinomyces had a pathological influence on tonsil size. This study showed there was a significant relation between Actinomyces and enlargement of tonsillar tissue. However, how causes tonsillar hypertrophy is not understood yet in tonsillar disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  8. Limited Relationship of Voltage Criteria for Electrocardiogram Left Ventricular Hypertrophy to Cardiovascular Mortality.

    Science.gov (United States)

    Ha, Le Dung; Elbadawi, Ayman; Froelicher, Victor F

    2018-01-01

    Numerous methods have been proposed for diagnosing left ventricular hypertrophy using the electrocardiogram. They have limited sensitivity for recognizing pathological hypertrophy, at least in part due to their inability to distinguish pathological from physiological hypertrophy. Our objective is to compare the major electrocardiogram-left ventricular hypertrophy criteria using cardiovascular mortality as a surrogate for pathological hypertrophy. This study was a retrospective analysis of 16,253 veterans electrocardiogram-left ventricular hypertrophy, and there were 744 cardiovascular deaths (annual cardiovascular mortality 0.25%). Receiver operating characteristic analysis demonstrated that the greatest area under the curve (AUC) for classification of cardiovascular death was obtained using the Romhilt-Estes score (0.63; 95% confidence interval, 0.61-0.65). Most of the voltage-only criteria had nondiagnostic area under the curves, with the Cornell being the best at 0.59 (95% confidence interval, 0.57-0.62). When the components of the Romhilt-Estes score were examined using step-wise Wald analysis, the voltage criteria dropped from the model. The Romhilt-Estes score ≥ 4, the Cornell, and the Peguero had the highest association with cardiovascular mortality (adjusted hazard ratios 2.2, 2.0, and 2.1, consecutively). None of the electrocardiogram leads with voltage criteria exhibited sufficient classification power for clinical use. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Systematic review of the synergist muscle ablation model for compensatory hypertrophy

    Directory of Open Access Journals (Sweden)

    Stella Maris Lins Terena

    Full Text Available Summary Objective: The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Method: Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. Results: The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. Conclusion: This model differs from other overload models (exercise and training regarding the characteristics involved in the hypertrophy process (acute and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

  10. Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS: evidence of adipocyte hypertrophy and tissue-specific inflammation.

    Directory of Open Access Journals (Sweden)

    Joseph S Marino

    Full Text Available Clinical research shows an association between polycystic ovary syndrome (PCOS and chronic inflammation, a pathological state thought to contribute to insulin resistance. The underlying pathways, however, have not been defined. The purpose of this study was to characterize the inflammatory state of a novel mouse model of PCOS. Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC mice and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. Tissue-specific macrophage infiltration and cytokine mRNA expression were measured, as well as circulating cytokine levels. Finally, glucose regulation during pregnancy was evaluated as a measure of risk for diabetes development. Forty-five percent of IR/LepR(POMC mice showed reduced or absent ovulation. IR/LepR(POMC mice also had increased fat mass and adipocyte hypertrophy. These traits accompanied elevations in macrophage accumulation and inflammatory cytokine production in perigonadal adipose tissue, liver, and ovary. These mice also exhibited gestational hyperglycemia as predicted. This report is the first to show the presence of inflammation in IR/LepR(POMC mice, which develop a PCOS-like phenotype. Thus, IR/LepR(POMC mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions.

  11. A High-Fat Diet Enriched with Low Omega-6 to Omega-3 Fatty Acid Ratio Reduced Fat Cellularity and Plasma Leptin Concentration in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    A. W. Tekeleselassie

    2013-01-01

    Full Text Available This study was aimed to investigate the effects of dietary fatty acids on the accretion pattern of major fat pads, inguinal fat cellularity, and their relation with plasma leptin concentration. Forty Sprague-Dawley rats were randomly assigned into four groups and received the following diets for 22 weeks: (1 standard rat chow diet (CTRL, (2 CTRL + 10% (w/w butter (HFAR, (3 CTRL + 3.33% (w/w menhaden fish oil + 6.67% (w/w soybean oil (MFAR, and (4 CTRL + 6.67% (w/w menhaden fish oil + 3.33% (w/w soybean oil (LFAR. Inguinal fat cellularity and plasma leptin concentration were measured in this study. Results for inguinal fat cellularity showed that the mean adipocyte number for the MFAR (9.2 * 105 ± 3.6 and LFAR (8.5 * 105 ± 5.1 groups was significantly higher (P<0.05 than the rest, while the mean adipocyte diameter of HFAR group was larger (P<0.05 (46.2 ± 2.8 than the rest. The plasma leptin concentration in the HFAR group was higher (P<0.05 (3.22 ± 0.32 ng/mL, than the other groups. The higher inguinal fat cellularity clearly indicated the ability of the polyunsaturated fatty acids (PUFA and butter supplemented diets to induce hyperplasia and hypertrophy of fat cells, respectively, which caused adipocyte remodeling due to hyperleptinemia.

  12. Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in prepubertal children

    DEFF Research Database (Denmark)

    Dencker, Magnus; Wollmer, Per; Karlsson, Magnus K

    2012-01-01

    Aim:  We analysed whether total body fat (TBF), abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods:  Cross-sectional study of 238 children aged 8-11 years. TBF and abdominal fat mass (AFM) were......, separately, and used as composite risk factor score. Results:  Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r = 0.56, r = 0.59 and r = 0.48, all p ...

  13. Surgical therapy for benign prostatic hypertrophy/bladder outflow obstruction

    Directory of Open Access Journals (Sweden)

    Nikesh Thiruchelvam

    2014-01-01

    Full Text Available Monopolar transurethral resection of the prostate (TURP with endoscopic electrocautery remains the gold standard surgical technique for benign prostatic hypertrophy (BPH by which all new procedures are compared. We reviewed the current literature, and international urological guidelines and consensus opinion on various surgical options for BPH and present a brief overview of alternative techniques including bipolar TURP, transurethral incision of the prostate, transurethral vaporization of the prostate, laser prostatectomy (with holmium, thulium and potassium titanyl phosphate greenlight lasers and open prostatectomy (with mention of new techniques including laparoscopic and robotic prostatectomy. Emerging, experimental and less established techniques are also described including endoscopic heat generation (transurethral microwave thermotherapy, radiofrequency transurethral needle ablation of the prostate, high intensity focused ultrasound, hot water induced thermotherapy, pulsed electromagnetic radiofrequency, injection therapy (transurethral ethanol ablation and botulinum toxin and mechanical devices (intraprostatic stents and urethral lift devices. Despite a plethora of surgical options, none have realistically improved outcomes in the long-term compared with TURP. Improvements have been made on improving surgical morbidity and time in hospital. Questions remain in this area, including what specific elements of bladder outflow obstruction (BOO result in damage to the urinary tract, how does BPH contribute to BOO and how much prostate volume reduction is necessary to relieve BOO or lower urinary tract symptoms. Given these unanswered questions and the multitude of procedures available, it is clear that appropriate counselling is necessary in all men who undergo BPH surgery.

  14. Active palpation sensor for detecting prostatic cancer and hypertrophy

    Science.gov (United States)

    Tanaka, Mami; Furubayashi, Mitsuyuki; Tanahashi, Yoshikatsu; Chonan, Seiji

    2001-03-01

    This paper is concerned with the development of an active palpation sensor for detecting the prostatic cancer and hypertrophy. The receptor of the sensor is a polyvinylidene fluoride (PVDF) film placed on the surface of a sponge rubber layer. It is mounted on a linear z-translation bar and inserted into the examinee's rectum being protected by a medical rubber glove. After positioned faced to the prostate gland, the sensor probe is driven sinusoidally at about 50Hz with peak-to-peak amplitude 2mm. The voltage signal from the PVDF film is integrated over the sampling period and used as the output of sensor for extracting the features of the collected data. The evaluation of stiffness by the sensor on 27 normal and unhealthy prostate glands are compared with the results of diagnosis by the doctor's palpation. It is shown that the output of sensor becomes greater with an increase of the stiffness of the prostate gland, which has good correlation with the doctor's evaluation on the stiffness. Further results on the laboratory test reconfirm that the present sensor well discriminates the stiffness of the prostate glands in vivo and non-invasively.

  15. Contact laser vaporization of the prostate for benign prostatic hypertrophy

    Science.gov (United States)

    Gomella, Leonard G.; Lotfi, M. A.; Milam, Douglas F.; Albala, David; Reagan, Gary

    1994-05-01

    The contact laser applications for the removal of the enlarged prostate are distinctly different than the majority of non-contact Nd:YAG lasers that rely on coagulation necrosis and delayed sloughing. Contact Nd:YAG laser allows cutting, coagulation and vaporization of tissue with minimal penetration beyond the contact surface. Using the contact laser prostatectomy technique, the contact laser probe directly touches and immediately vaporizes the prostatic tissue under the probe. The net result is the immediate removal of the obstructing tissue, in a manner similar to the standard electrosurgical TURP. This immediate removal of tissue offers the patient treated with the contact laser the potential for decreased catheter time and a more rapid resolution of symptoms. Our initial experience suggests that the contact technique may be better suited for the smaller prostate gland (i.e. less than 30 gm). The contact laser may also be used for a procedure termed the `laser assisted TURP': a standard electrosurgical TURP is performed and the contact laser is used for hemostasis. Several investigators have reported non-randomized results of the contact technique with good outcomes. A prospective randomized trial of the contact laser prostatectomy vrs the electrosurgical TURP is underway. The contact laser vaporization of the prostate holds great promise for the treatment of symptomatic benign prostatic hypertrophy: it is virtually bloodless and allows immediate visualization of the TUR defect.

  16. PERIOPERATIVE PERIOD FOLLOWING HEART TRANSPLANTATION WITH SEVERE LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2012-01-01

    Full Text Available Use donor hearts with left ventricular hypertrophy (LVH is controversial. This category of heart recipients has increasing risk of early graft failure. We proposed that heart transplantation (HT with LVH ≥1.5 cm may be successful if performed in selective category patients from alternate transplant list. This study included 10 pati- ents (2 female and 8 male at the age 26–62 (44 ± 3, who needed urgent HT. This study showed that recipients with LVH ≥1.5 cm demanded more high and long inotropic support with adrenalin and dopamine, more fre- quent use of levosimendan infusion (in 40% of cases and intraaortic balloon conterpulsation (in 50% of cases. However we didn’t observed any difference in survival rate (90.0% vs 89.0% and ICU time (4.8 ± 0.6 days vs 4.1 ± 0.4 days between HT recipients with and without LVH. Our study showed that HT from donor with LVH ≥1.5 cm may be performed in patients, demanding urgent HT, with acceptable early posttransplant results. 

  17. Hypertrophy of the breast: a problem of beauty or health?

    Science.gov (United States)

    Benditte-Klepetko, Heike; Leisser, Valerie; Paternostro-Sluga, Tatjana; Rakos, Monika; Trattnig, Siegfried; Helbich, Thomas; Schemper, Michael; Deutinger, Maria

    2007-09-01

    Despite the complex health burden for women with breast hypertrophy, medical directors of health insurance companies are not convinced that this procedure is of medical benefit for patients. Therefore, coverage of cost by the health insurance companies is no longer guaranteed. The purpose of this study is to evaluate the influence of breast weight on the physical and psychological morbidity of women and to prove the medical necessity of reduction mammaplasty. We performed a cohort study of 50 women with various breast sizes, a mean age of 28 years (range 20-40 years), and a body mass index (BMI) <25. Breast weight was measured, the spine was investigated by magnetic resonance imaging (MRI), and a spine score of clinical symptoms was assessed. The Beck Depression Inventory (BDI) was used to evaluate psychological impairment. Pathological findings have been correlated with breast weight, and the risk of developing a morphological or psychological disorder independence of the breast weight was calculated. The incidence of degenerative spine disorders and the extent of depressive symptoms are correlated with increasing breast weight. The data show that high breast weight has a negative influence on the physical and psychological morbidity of women. This objective evidence in support of the medical necessity of reduction mammaplasty should guide managed care organizations' methods for determining coverage for reduction mammaplasty.

  18. Integrin activation and focal complex formation in cardiac hypertrophy

    Science.gov (United States)

    Laser, M.; Willey, C. D.; Jiang, W.; Cooper, G. 4th; Menick, D. R.; Zile, M. R.; Kuppuswamy, D.

    2000-01-01

    Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

  19. The role of dietary fatty acids in predicting myocardial structure in fat-fed rats

    Directory of Open Access Journals (Sweden)

    Miller Melissa L

    2011-06-01

    high-fat feeding. These findings suggest that myocyte hypertrophy may be an early change leading to gross LV hypertrophy in the hearts of "healthy" obese rats, in the absence of hypertension, diabetes and myocardial ischemia.

  20. Oil and fat absorbing polymers

    Science.gov (United States)

    Marsh, H. E., Jr. (Inventor)

    1977-01-01

    A method is described for forming a solid network polymer having a minimal amount of crosslinking for use in absorbing fats and oils. The polymer remains solid at a swelling ratio in oil or fat of at least ten and provides an oil absorption greater than 900 weight percent.

  1. Fats and oils: An overview

    Science.gov (United States)

    Dietary fat is a macronutrient that has historically engendered considerable controversy and continues to do so. Contentious areas include optimal amount and type for cardiovascular disease risk reduction, and role in body weight regulation. Dietary fats and oils are unique in modern times in that ...

  2. Cardiac function and lipid distribution in rats fed a high-fat diet: in vivo magnetic resonance imaging and spectroscopy.

    Science.gov (United States)

    Nagarajan, Vijayasarathi; Gopalan, Venkatesh; Kaneko, Manami; Angeli, Veronique; Gluckman, Peter; Richards, Arthur Mark; Kuchel, Philip W; Velan, S Sendhil

    2013-06-01

    Obesity is a major risk factor in the development of cardiovascular disease, type 2 diabetes, and its pathophysiological precondition insulin resistance. Very little is known about the metabolic changes that occur in the myocardium and consequent changes in cardiac function that are associated with high-fat accumulation. Therefore, cardiac function and metabolism were evaluated in control rats and those fed a high-fat diet, using magnetic resonance imaging, magnetic resonance spectroscopy, mRNA analysis, histology, and plasma biochemistry. Analysis of blood plasma from rats fed the high-fat diet showed that they were insulin resistant (P biochemistry, magnetic resonance imaging, and mRNA analysis confirmed that rats on the high-fat diet had moderate diabetes along with mild cardiac hypertrophy. The magnetic resonance spectroscopy results showed the extramyocellular lipid signal only in the spectra from high-fat diet rats, which was absent in the control diet rats. The intramyocellular lipids in high-fat diet rats was higher (8.7%) compared with rats on the control diet (6.1%). This was confirmed by electron microscope and light microscopy studies. Our results indicate that lipid accumulation in the myocardium might be an early indication of the cardiovascular pathophysiology associated with type 2 diabetes.

  3. Fat burners: nutrition supplements that increase fat metabolism.

    Science.gov (United States)

    Jeukendrup, A E; Randell, R

    2011-10-01

    The term 'fat burner' is used to describe nutrition supplements that are claimed to acutely increase fat metabolism or energy expenditure, impair fat absorption, increase weight loss, increase fat oxidation during exercise, or somehow cause long-term adaptations that promote fat metabolism. Often, these supplements contain a number of ingredients, each with its own proposed mechanism of action and it is often claimed that the combination of these substances will have additive effects. The list of supplements that are claimed to increase or improve fat metabolism is long; the most popular supplements include caffeine, carnitine, green tea, conjugated linoleic acid, forskolin, chromium, kelp and fucoxanthin. In this review the evidence for some of these supplements is briefly summarized. Based on the available literature, caffeine and green tea have data to back up its fat metabolism-enhancing properties. For many other supplements, although some show some promise, evidence is lacking. The list of supplements is industry-driven and is likely to grow at a rate that is not matched by a similar increase in scientific underpinning. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

  4. Expression profiling reveals differences in metabolic gene expression between exercise-induced cardiac effects and maladaptive cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strøm, Claes C; Aplin, Mark; Ploug, Thorkil

    2005-01-01

    While cardiac hypertrophy elicited by pathological stimuli eventually leads to cardiac dysfunction, exercise-induced hypertrophy does not. This suggests that a beneficial hypertrophic phenotype exists. In search of an underlying molecular substrate we used microarray technology to identify cardiac...... by quantitative PCR. The exercise program resulted in cardiac hypertrophy without impaired cardiac function. Principal component analysis identified an exercise-induced change in gene expression that was distinct from the program observed in maladaptive hypertrophy. Statistical analysis identified 267 upregulated...... translocase (CD36). DNA microarray analysis of gene expression changes in exercise-induced cardiac hypertrophy suggests that a set of genes involved in fatty acid and glucose metabolism could be fundamental to the beneficial phenotype of exercise-induced hypertrophy, as these changes are absent or reversed...

  5. Omega-3 fats: Good for your heart

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000767.htm Omega-3 fats: Good for your heart To use the sharing ... 3 fatty acids are a type of polyunsaturated fat . We need these fats to build brain cells ...

  6. History of fat grafting: from ram fat to stem cells.

    Science.gov (United States)

    Mazzola, Riccardo F; Mazzola, Isabella C

    2015-04-01

    Fat injection empirically started 100 years ago to correct contour deformities mainly on the face and breast. The German surgeon Eugene Hollaender (1867-1932) proposed a cocktail of human and ram fat, to avoid reabsorption. Nowadays, fat injection has evolved, and it ranks among the most popular procedures, for it provides the physician with a range of aesthetic and reconstructive clinical applications with regenerative effects on the surrounding tissues. New research from all over the world has demonstrated the role of adipose-derived stem cells, present in the adipose tissue, in the repair of damaged or missing tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Factors influencing left ventricular hypertrophy in children and adolescents with or without family history of premature myocardial infarction

    Directory of Open Access Journals (Sweden)

    Seyyed Mohsen Hosseini

    2014-01-01

    Result : The results showed that among the studied variables, gender, age, body mass index, and blood pressure were associated with the left ventricular hypertrophy. Conclusion: Considering the results and previous studies in this field, it was observed that left ventricular hypertrophy exists at early ages, which is very dangerous and can lead to heart diseases at early ages. Factors such as being overweight, having high blood pressure, and being male cause left ventricular hypertrophy and lead to undiagnosable heart diseases.

  8. Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

    Science.gov (United States)

    Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

    2015-03-18

    Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright

  9. Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

    Directory of Open Access Journals (Sweden)

    Chiaki Nagai-Okatani

    Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

  10. Autophagy Plays an Essential Role in Mediating Regression of Hypertrophy during Unloading of the Heart

    Science.gov (United States)

    Hariharan, Nirmala; Ikeda, Yoshiyuki; Hong, Chull; Alcendor, Ralph R.; Usui, Soichiro; Gao, Shumin; Maejima, Yasuhiro; Sadoshima, Junichi

    2013-01-01

    Autophagy is a bulk degradation mechanism for cytosolic proteins and organelles. The heart undergoes hypertrophy in response to mechanical load but hypertrophy can regress upon unloading. We hypothesize that autophagy plays an important role in mediating regression of cardiac hypertrophy during unloading. Mice were subjected to transverse aortic constriction (TAC) for 1 week, after which the constriction was removed (DeTAC). Regression of cardiac hypertrophy was observed after DeTAC, as indicated by reduction of LVW/BW and cardiomyocyte cross-sectional area. Indicators of autophagy, including LC3-II expression, p62 degradation and GFP-LC3 dots/cell, were significantly increased after DeTAC, suggesting that autophagy is induced. Stimulation of autophagy during DeTAC was accompanied by upregulation of FoxO1. Upregulation of FoxO1 and autophagy was also observed in vitro when cultured cardiomyocytes were subjected to mechanical stretch followed by incubation without stretch (de-stretch). Transgenic mice with cardiac-specific overexpression of FoxO1 exhibited smaller hearts and upregulation of autophagy. Overexpression of FoxO1 in cultured cardiomyocytes significantly reduced cell size, an effect which was attenuated when autophagy was inhibited. To further examine the role of autophagy and FoxO1 in mediating the regression of cardiac hypertrophy, beclin1+/− mice and cultured cardiomyocytes transduced with adenoviruses harboring shRNA-beclin1 or shRNA-FoxO1 were subjected to TAC/stretch followed by DeTAC/de-stretch. Regression of cardiac hypertrophy achieved after DeTAC/de-stretch was significantly attenuated when autophagy was suppressed through downregulation of beclin1 or FoxO1. These results suggest that autophagy and FoxO1 play an essential role in mediating regression of cardiac hypertrophy during mechanical unloading. PMID:23308102

  11. The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy

    Science.gov (United States)

    Aronsen, Jan Magnus; Ferrini, Arianna; Brien, Patrick; Alkass, Kanar; Tomasso, Antonio; Agrawal, Asmita; Bergmann, Olaf; Reik, Wolf; Roderick, Hywel Llewelyn

    2016-01-01

    Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes. This analysis revealed the pervasive loss of euchromatic H3K9me2 as a conserved feature of pathological hypertrophy that was associated with reexpression of fetal genes. In hypertrophy, H3K9me2 was reduced following a miR-217–mediated decrease in expression of the H3K9 dimethyltransferases EHMT1 and EHMT2 (EHMT1/2). miR-217–mediated, genetic, or pharmacological inactivation of EHMT1/2 was sufficient to promote pathological hypertrophy and fetal gene reexpression, while suppression of this pathway protected against pathological hypertrophy both in vitro and in mice. Thus, we have established a conserved mechanism involving a departure of the cardiomyocyte epigenome from its adult cellular identity to a reprogrammed state that is accompanied by reexpression of fetal genes and pathological hypertrophy. These results suggest that targeting miR-217 and EHMT1/2 to prevent H3K9 methylation loss is a viable therapeutic approach for the treatment of heart disease. PMID:27893464

  12. Comparison of Electrocardiographic Criteria for Identifying Left Ventricular Hypertrophy in Athletes from Different Sports Modalities

    Directory of Open Access Journals (Sweden)

    Nelson Samesima

    Full Text Available OBJECTIVES: In athletes, isolated electrocardiogram high voltage criteria are widely used to evaluate left ventricular hypertrophy, but positive findings are thought to represent normal electrocardiogram alterations. However, which electrocardiogram criterion can best detect left ventricular hypertrophy in athletes of various sport modalities remains unknown. METHODS: Five electrocardiogram criteria used to detect left ventricular hypertrophy were tested in 180 male athletes grouped according to their sport modality: 67% low-static and high-dynamic components and 33% high-static and high-dynamic components of exercise. The following echocardiogram parameters are the gold standard for diagnosing left ventricular hypertrophy: left ventricular mass index ≥134 g.m-2, relative wall thickness ≥0.42 mm, left ventricular diastolic diameter index ≥32 mm.m-2, septum wall thickness ≥13 mm, and posterior wall thickness ≥13 mm. Results for the various criteria were compared using the kappa coefficient. Significance was established at p<0.05. RESULTS: Fifty athletes (28% presented with left ventricular hypertrophy according to electrocardiogram findings, with the following sensitivities and specificities, respectively: 38-53% and 79-83% (Perugia, 22-40% and 89-91% (Cornell, 24-29% and 90% (Romhilt-Estes, 68-87% and 20-23% (Sokolow-Lyon, and 0% and 99% (Gubner. The Perugia and Cornell criteria had higher negative predictive values for the low-static and high-dynamic subgroup. Kappa coefficients were higher for Romhilt-Estes, Cornell and Perugia criteria than for Sokolow-Lyon and Gubner criteria. CONCLUSION: All five evaluated criteria are inadequate for detecting left ventricular hypertrophy, but the Perugia, Cornell and Romhilt-Estes criteria are useful for excluding its presence. The Perugia and Cornell criteria were more effective at excluding left ventricular hypertrophy in athletes involved in a sport modality with low-static and high

  13. Atrial Fibrillation in Hypertrophic Cardiomyopathy: Is the Extent of Septal Hypertrophy Important?

    Science.gov (United States)

    Park, Kyoung-Min; Im, Sung Il; Kim, Eun Kyoung; Lee, Sang-Chol; Park, Seung-Jung; Kim, June Soo; On, Young Keun

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a cardiac disease associated with a high incidence of atrial fibrillation (AF). Recent studies have suggested that interventricular septum thickness may influence the risk stratification of patients with AF. We evaluated the effects of septal hypertrophy on morbidity and mortality in patients with HCM. Patients were followed for a median of 6.1 years and were divided into two groups according to the extent of septal hypertrophy. A total of 1,360 HCM patients were enrolled: 482 (33%) apical or apicoseptal, 415 (28%) asymmetric septal, 388 (27%) basal septal, 38 (2.6%) concentric, and 37 (2.5%) diffuse and mixed type. Ninety-two all-cause deaths and 21 cardiac deaths occurred. The total event rates were significantly higher for patients with HCM with more extensive septal hypertrophy (group A) compared to those with HCM ± focal septal hypertrophy (group B), regardless of type (p<0.001). Arrhythmias occurred in 502 patients, with a significantly higher incidence in group A than in group B (p<0.001). Among patients with arrhythmias, the incidence of AF was significantly higher in group A than group B (p<0.001). In univariate Cox analysis, a greater extent of septal hypertrophy (p<0.001), E/E´ ratio (p = 0.011), and mitral regurgitation grade (p = 0.003) were significantly associated with developing AF. In multivariate Cox analyses, a greater extent of septal hypertrophy [odds ratio (OR) 5.44 (2.29-12.92), p<0.001] in patients with HCM was significantly associated with developing AF. In conclusion, a greater extent of septal hypertrophy is an independent predictor of progression to AF in patients with HCM.

  14. Loss of cardiac carnitine palmitoyltransferase 2 results in rapamycin-resistant, acetylation-independent hypertrophy.

    Science.gov (United States)

    Pereyra, Andrea S; Hasek, Like Y; Harris, Kate L; Berman, Alycia G; Damen, Frederick W; Goergen, Craig J; Ellis, Jessica M

    2017-11-10

    Cardiac hypertrophy is closely linked to impaired fatty acid oxidation, but the molecular basis of this link is unclear. Here, we investigated the loss of an obligate enzyme in mitochondrial long-chain fatty acid oxidation, carnitine palmitoyltransferase 2 (CPT2), on muscle and heart structure, function, and molecular signatures in a muscle- and heart-specific CPT2-deficient mouse (Cpt2 M-/- ) model. CPT2 loss in heart and muscle reduced complete oxidation of long-chain fatty acids by 87 and 69%, respectively, without altering body weight, energy expenditure, respiratory quotient, or adiposity. Cpt2M -/- mice developed cardiac hypertrophy and systolic dysfunction, evidenced by a 5-fold greater heart mass, 60-90% reduction in blood ejection fraction relative to control mice, and eventual lethality in the absence of cardiac fibrosis. The hypertrophy-inducing mammalian target of rapamycin complex 1 (mTORC1) pathway was activated in Cpt2M -/- hearts; however, daily rapamycin exposure failed to attenuate hypertrophy in Cpt2M -/- mice. Lysine acetylation was reduced by ∼50% in Cpt2M -/- hearts, but trichostatin A, a histone deacetylase inhibitor that improves cardiac remodeling, failed to attenuate Cpt2M -/- hypertrophy. Strikingly, a ketogenic diet increased lysine acetylation in Cpt2M -/- hearts 2.3-fold compared with littermate control mice fed a ketogenic diet, yet it did not improve cardiac hypertrophy. Together, these results suggest that a shift away from mitochondrial fatty acid oxidation initiates deleterious hypertrophic cardiac remodeling independent of fibrosis. The data also indicate that CPT2-deficient hearts are impervious to hypertrophy attenuators, that mitochondrial metabolism regulates cardiac acetylation, and that signals derived from alterations in mitochondrial metabolism are the key mediators of cardiac hypertrophic growth. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy.

    Science.gov (United States)

    Seok, Hee Young; Chen, Jinghai; Kataoka, Masaharu; Huang, Zhan-Peng; Ding, Jian; Yan, Jinglu; Hu, Xiaoyun; Wang, Da-Zhi

    2014-05-09

    In response to mechanical and pathological stress, adult mammalian hearts often undergo mal-remodeling, a process commonly characterized as pathological hypertrophy, which is associated with upregulation of fetal genes, increased fibrosis, and reduction of cardiac dysfunction. The molecular pathways that regulate this process are not fully understood. To explore the function of microRNA-155 (miR-155) in cardiac hypertrophy and remodeling. Our previous work identified miR-155 as a critical microRNA that repressed the expression and function of the myocyte enhancer factor 2A. In this study, we found that miR-155 is expressed in cardiomyocytes and that its expression is reduced in pressure overload-induced hypertrophic hearts. In mouse models of cardiac hypertrophy, miR-155 null hearts suppressed cardiac hypertrophy and cardiac remodeling in response to 2 independent pathological stressors, transverse aortic restriction and an activated calcineurin transgene. Most importantly, loss of miR-155 prevents the progress of heart failure and substantially extends the survival of calcineurin transgenic mice. The function of miR-155 in hypertrophy is confirmed in isolated cardiomyocytes. We identified jumonji, AT rich interactive domain 2 (Jarid2) as an miR-155 target in the heart. miR-155 directly represses Jarid2, whose expression is increased in miR-155 null hearts. Inhibition of endogenous Jarid2 partially rescues the effect of miR-155 loss in isolated cardiomyocytes. Our studies uncover miR-155 as an inducer of pathological cardiomyocyte hypertrophy and suggest that inhibition of endogenous miR-155 might have clinical potential to suppress cardiac hypertrophy and heart failure.

  16. Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy.

    Science.gov (United States)

    Cipolletta, Ersilia; Rusciano, Maria Rosaria; Maione, Angela Serena; Santulli, Gaetano; Sorriento, Daniela; Del Giudice, Carmine; Ciccarelli, Michele; Franco, Antonietta; Crola, Catherine; Campiglia, Pietro; Sala, Marina; Gomez-Monterrey, Isabel; De Luca, Nicola; Trimarco, Bruno; Iaccarino, Guido; Illario, Maddalena

    2015-01-01

    Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy through ERK nuclear localization. In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17β, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE)-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17β pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17β. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart. These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy.

  17. 19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy.

    Science.gov (United States)

    Elkhatali, Samya; El-Sherbeni, Ahmed A; Elshenawy, Osama H; Abdelhamid, Ghada; El-Kadi, Ayman O S

    2015-12-15

    We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague-Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography-mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

    Science.gov (United States)

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl) diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl) diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

  19. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

  20. Trans fats: What physicians should know

    OpenAIRE

    Marchand, V

    2010-01-01

    Hydrogenation of fat products is used in the food industry to extend their shelf life. Trans fats are the result of partial hydrogenation of unsaturated fat. Trans fats increase low-density lipoprotein cholesterol and decrease high-density lipoprotein cholesterol, thus increasing the risk of cardiovascular disease. Canadians have one of the highest dietary intake of trans fat in the world. Health Canada has made recommendations to decrease the trans fat intake of Canadians. Physicians should ...

  1. TDP-43, an ALS linked protein, regulates fat deposition and glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Nancy R Stallings

    Full Text Available The identification of proteins which determine fat and lean body mass composition is critical to better understanding and treating human obesity. TDP-43 is a well-conserved RNA-binding protein known to regulate alternative splicing and recently implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS. While TDP-43 knockout mice show early embryonic lethality, post-natal conditional knockout mice show weight loss, fat depletion, and rapid death, suggesting an important role for TDP-43 in regulating energy metabolism. Here we report, that over-expression of TDP-43 in transgenic mice can result in a phenotype characterized by increased fat deposition and adipocyte hypertrophy. In addition, TDP-43 over-expression in skeletal muscle results in increased steady state levels of Tbc1d1, a RAB-GTPase activating protein involved in Glucose 4 transporter (Glut4 translocation. Skeletal muscle fibers isolated from TDP-43 transgenic mice show altered Glut4 translocation in response to insulin and impaired insulin mediated glucose uptake. These results indicate that levels of TDP-43 regulate body fat composition and glucose homeostasis in vivo.

  2. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity.

    Science.gov (United States)

    Martins, Fernando; Campos, Dijon Henrique Salomé; Pagan, Luana Urbano; Martinez, Paula Felippe; Okoshi, Katashi; Okoshi, Marina Politi; Padovani, Carlos Roberto; Souza, Albert Schiaveto de; Cicogna, Antonio Carlos; Oliveira-Junior, Silvio Assis de

    2015-11-01

    Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity. To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet. Sixteen Wistar rats were used, distributed into two groups, the control (C) group, treated with isocaloric diet (2.93 kcal/g) and an obese (OB) group, treated with high-fat diet (3.64 kcal/g). The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed. High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained. It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

  3. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity

    Directory of Open Access Journals (Sweden)

    Fernando Martins

    2015-01-01

    Full Text Available AbstractBackground:Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity.Objective:To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet.Methods:Sixteen Wistar rats were used, distributed into two groups, the control (C group, treated with isocaloric diet (2.93 kcal/g and an obese (OB group, treated with high-fat diet (3.64 kcal/g. The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed.Results:High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained.Conclusion:It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

  4. Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Piva e Mattos, Beatriz; Torres, Marco Antonio Rodrigues; Freitas, Valéria Centeno de; Scolari, Fernando Luís; Loreto, Melina Silva de

    2013-05-01

    In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias. In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holter) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI). Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT). In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m²), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m²) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04). In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

  5. Vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin.

    Science.gov (United States)

    Peiró, C; Angulo, J; Rodríguez-Mañas, L; Llergo, J L; Vallejo, S; Cercas, E; Sánchez-Ferrer, C F

    1998-10-01

    1. Nonenzymatic protein glycosylation is a possible mechanism contributing to oxidative stress and vascular disease in diabetes. In this work, the influence of 14%-glycosylated human oxyhaemoglobin (GHHb), compared to the non-glycosylated protein (HHb), was studied on several growth parameters of rat cultured vascular smooth muscle cells (VSMC). A role for reactive oxygen species was also analysed. 2. Treatment of VSMC for 48 h with GHHb, but not with HHb, increased planar cell surface area in a concentration dependent manner. The threshold concentration was 10 nM, which increased cell size from 7965+/-176 to 9411+/-392 microm2. Similarly, only GHHb enhanced protein content per well in VSMC cultures. 3. The planar surface area increase induced by 10 nM GHHb was abolished by superoxide dismutase (SOD; 50 200 u ml(-1)), deferoxamine (100 nM-100 microM), or dimethylthiourea (1 mM), while catalase (50 200 u ml(-1)) or mannitol (1 mM) resulted in a partial inhibition of cell size enhancement. 4. When a known source of oxygen free radicals was administered to VSMC, the xanthine/xanthine oxidase system, the results were analogous to those produced by GHHb. Indeed, enhancements of cell size were observed, which were inhibited by SOD, deferoxamine, or catalase. 5. These results indicate that, at low concentrations, GHHb induces hypertrophy in VSMC, this effect being mediated by superoxide anions, hydrogen peroxide, and/or hydroxyl radicals. Therefore, glycosylated proteins can have a role in the development of the structural vascular alterations associated to diabetes by enhancing oxidative stress.

  6. Vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin

    Science.gov (United States)

    Peiró, Concepción; Angulo, Javier; Rodríguez-Mañas, Leocadio; Llergo, José L; Vallejo, Susana; Cercas, Elena; Sánchez-Ferrer, Carlos F

    1998-01-01

    Nonenzymatic protein glycosylation is a possible mechanism contributing to oxidative stress and vascular disease in diabetes. In this work, the influence of 14%-glycosylated human oxyhaemoglobin (GHHb), compared to the non-glycosylated protein (HHb), was studied on several growth parameters of rat cultured vascular smooth muscle cells (VSMC). A role for reactive oxygen species was also analysed.Treatment of VSMC for 48 h with GHHb, but not with HHb, increased planar cell surface area in a concentration dependent manner. The threshold concentration was 10 nM, which increased cell size from 7965±176 to 9411±392 μm2. Similarly, only GHHb enhanced protein content per well in VSMC cultures.The planar surface area increase induced by 10 nM GHHb was abolished by superoxide dismutase (SOD; 50–200 u ml−1), deferoxamine (100 nM–100 μM), or dimethylthiourea (1 mM), while catalase (50–200 u ml−1) or mannitol (1 mM) resulted in a partial inhibition of cell size enhancement.When a known source of oxygen free radicals was administered to VSMC, the xanthine/xanthine oxidase system, the results were analogous to those produced by GHHb. Indeed, enhancements of cell size were observed, which were inhibited by SOD, deferoxamine, or catalase.These results indicate that, at low concentrations, GHHb induces hypertrophy in VSMC, this effect being mediated by superoxide anions, hydrogen peroxide, and/or hydroxyl radicals. Therefore, glycosylated proteins can have a role in the development of the structural vascular alterations associated to diabetes by enhancing oxidative stress. PMID:9831896

  7. Mechanisms of cardiac hypertrophy in canine volume overload

    Science.gov (United States)

    Matsuo, T.; Carabello, B. A.; Nagatomo, Y.; Koide, M.; Hamawaki, M.; Zile, M. R.; McDermott, P. J.

    1998-01-01

    This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small change in the rate of protein synthesis or, alternatively, is due to a decreased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ratio increased by 23% compared with baseline values. This increase in LV mass occurred with a small, but not statistically significant, increase in the fractional rate of myosin heavy chain (MHC) synthesis (Ks), as measured using continuous infusion with [3H]leucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Translational efficiency was unaffected by mitral regurgitation as measured by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measured by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mitral regurgitation. Most of the growth after mitral regurgitation was accounted for by a decrease in the fractional rate of protein degradation, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding Ks values. We conclude that 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in the rate of protein degradation.

  8. Left ventricular hypertrophy as a predictor of cardiovascular risk.

    Science.gov (United States)

    Gosse, Philippe

    2005-04-01

    Left ventricular hypertrophy (LVH) is a potent, independent predictor of cardiovascular events, particularly in hypertension, in which it dramatically increases the risk of stroke, coronary heart disease and heart failure. LVH is predominantly a surrogate marker for the effects of other risk factors integrated over time, but it may also contribute directly to cardiovascular disease through pathological changes in cardiac structure. The influence of blood pressure is central to LVH pathology, with 24-h blood pressure being more predictive of LVH than single clinic measurements. Blood pressure variation throughout the day is also emerging as an important correlate of LVH, and a strong association has been found between the early morning blood pressure rise and increased left ventricular mass. Antihypertensive treatment can reverse LVH, and preliminary studies suggest that this improves cardiovascular outcome and long-term prognosis. Most classes of antihypertensive agent show some effect on LVH regression, with the notable exceptions of minoxidil and hydralazine. However, many of the data regarding LVH regression come from small, poor-quality trials or from meta-analyses of these studies. In the few well-conducted studies that are available, certain classes of antihypertensive drugs are more effective than others. Those that target angiotensin II, such as the angiotensin II receptor blockers, appear to have a specific action on LVH that is independent of blood pressure reduction. Further high-quality studies are needed to define how LVH predicts cardiovascular risk, which agents are most effective at eliciting LVH regression and how such reversal can affect cardiovascular outcome.

  9. Magnetic resonance imaging of autologous fat grafting

    Energy Technology Data Exchange (ETDEWEB)

    Goehde, Susanne C.; Kuehl, Hilmar; Ladd, Mark E. [University Hospital Essen, Department of Diagnostic and Interventional Radiology, Essen (Germany)

    2005-12-01

    A 30-year-old female patient with isolated facial lipodystrophy underwent two sessions of fat injection. MR signals of injected fat at different injection ages were compared to native fat. Native T1 signal was smaller for transplant fat, probably due to a slightly lower fat content and/or fibrosis or due to higher perfusion. T2 signal of transplants was significantly higher than that of native fat. T1 post-contrast was also higher, and contrast uptake of transplanted fat increased slightly with transplant age, which could be explained by an increasing perfusion. This study demonstrates the differences and MR signal time changes of native and transplanted fat. (orig.)

  10. Mesotherapy for local fat reduction.

    Science.gov (United States)

    Jayasinghe, S; Guillot, T; Bissoon, L; Greenway, F

    2013-10-01

    Mesotherapy, which is the injection of substances locally into mesodermally derived subcutaneous tissue, developed from empirical observations of a French physician in the 1950s. Although popular in Europe for many medical purposes, it is used for local cosmetic fat reduction in the United States. This paper reviews manuscripts indexed in PubMed/MEDLINE under 'mesotherapy', which pertains to local fat reduction. The history of lipolytic mesotherapy, the physiology of body fat distribution, the mechanism of action of different lipolytic stimulators and their increased efficacy in combination are reviewed. Mesotherapy falls into two categories. Lipolytic mesotherapy using lipolytic stimulators requires more frequent treatments as the fat cells are not destroyed and can refill over time. Ablative mesotherapy destroys fat cells with a detergent, causes inflammation and scarring from the fat necrosis, but requires fewer treatments. The historic and empiric mixing of sodium channel blocking local anaesthetics in mesotherapy solutions inhibits the intended lipolysis. Major mesotherapy safety concerns include injection site infections from poor sterile technique. Cosmetic mesotherapy directs the area from which fat is lost to improve self-image. Studies were of relatively small number, many with limited sample sizes. Future research should be directed towards achieving a Food and Drug Administration indication rather than continuing expansion of off-label use. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  11. A novel approach in the use of radiofrequency catheter ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Abhijeet B. Shelke

    2016-09-01

    Conclusion: RFCA of the hypertrophied septum causes sustained reduction in the LVOT gradient and symptomatic improvement among patients with HOCM. Electroanatomical mapping helps to perform the procedure safely.

  12. Determination of Fat Content

    Science.gov (United States)

    Carpenter, Charles

    The term "lipid" refers to a group of compounds that are sparingly soluble in water, but show variable solubility in a number of organic solvents (e.g., ethyl ether, petroleum ether, acetone, ethanol, methanol, benzene). The lipid content of a food determined by extraction with one solvent may be quite different from the lipid content as determined with another solvent of different polarity. Fat content is determined often by solvent extraction methods (e.g., Soxhlet, Goldfish, Mojonnier), but it also can be determined by nonsolvent wet extraction methods (e.g., Babcock, Gerber), and by instrumental methods that rely on the physical and chemical properties of lipids (e.g., infrared, density, X-ray absorption). The method of choice depends on a variety of factors, including the nature of the sample (e.g., dry versus moist), the purpose of the analysis (e.g., official nutrition labeling or rapid quality control), and instrumentation available (e.g., Babcock uses simple glassware and equipment; infrared requires an expensive instrument).

  13. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  14. RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model.

    Directory of Open Access Journals (Sweden)

    Praful Aggarwal

    Full Text Available Cardiac hypertrophy is an independent risk factor for cardiovascular disease and heart failure. There is increasing evidence that microRNAs (miRNAs play an important role in the regulation of messenger RNA (mRNA and the pathogenesis of various cardiovascular diseases. However, the ability to comprehensively study cardiac hypertrophy on a gene regulatory level is impacted by the limited availability of human cardiomyocytes. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs offer the opportunity for disease modeling. Here we utilize a previously established in vitro model of cardiac hypertrophy to interrogate the regulatory mechanism associated with the cardiac disease process. We perform miRNA sequencing and mRNA expression analysis on endothelin 1 (ET-1 stimulated hiPSC-CMs to describe associated RNA expression profiles. MicroRNA sequencing revealed over 250 known and 34 predicted novel miRNAs to be differentially expressed between ET-1 stimulated and unstimulated control hiPSC-CMs. Messenger RNA expression analysis identified 731 probe sets with significant differential expression. Computational target prediction on significant differentially expressed miRNAs and mRNAs identified nearly 2000 target pairs. A principal component analysis approach comparing the in vitro data with human myocardial biopsies detected overlapping expression changes between the in vitro samples and myocardial biopsies with Left Ventricular Hypertrophy. These results provide further insights into the complex RNA regulatory mechanism associated with cardiac hypertrophy.

  15. Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

    Directory of Open Access Journals (Sweden)

    Celso Ferreira Filho

    2010-01-01

    Full Text Available OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed, Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor and verapamil (Ca++ channel blocker caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker were similar. Indapamina (diuretic had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1 receptor antagonist produced better results than atenolol (selective β1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

  16. Lumbar radiculopathy due to unilateral facet hypertrophy following lumbar disc hernia operation: a case report.

    Science.gov (United States)

    Kökeş, Fatih; Günaydin, Ahmet; Aciduman, Ahmet; Kalan, Mehmet; Koçak, Halit

    2007-10-01

    To present a radiculopathy case due to unilateral facet hypertrophy developing three years after a lumbar disc hernia operation. A fifty two-year-old female patient, who had been operated on for a left L5-S1 herniated lumbar disc three years ago, was hospitalized and re-operated with a diagnosis of unilateral facet hypertrophy. She had complaints of left leg pain and walking restrictions for the last six months. Left Straight Leg Raising test was positive at 40 degrees , left ankle dorsiflexion muscle strength was 4/5, left Extensor Hallucis Longus muscle strength was 3/5, and left Achilles reflex was hypoactive. Lumbar spinal Magnetic Resonance Imaging revealed left L5-S1 facet hypertrophy. Lumbar radiculopathy due to lumbar facet hypertrophy is a well-known neurological condition. Radicular pain develops during the late postoperative period following lumbar disc hernia operations that are often related to recurrent disc herniation or to formation of post-operative scar tissue. In addition, it can be speculated that unilateral facet hypertrophy, which may develop after a disc hernia operation, might also be one of the causes of radiculopathy.

  17. Antiandrogenic therapy with finasteride attenuates cardiac hypertrophy and left ventricular dysfunction.

    Science.gov (United States)

    Zwadlo, Carolin; Schmidtmann, Elisa; Szaroszyk, Malgorzata; Kattih, Badder; Froese, Natali; Hinz, Hebke; Schmitto, Jan Dieter; Widder, Julian; Batkai, Sandor; Bähre, Heike; Kaever, Volkhard; Thum, Thomas; Bauersachs, Johann; Heineke, Joerg

    2015-03-24

    In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure. We found a strongly induced expression of all 3 isoforms of the 5-α-reductase (Srd5a1 to Srd5a3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of dihydrotestosterone. Starting 1 week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were markedly improved in response to finasteride treatment in not only male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride, by decreasing dihydrotestosterone, potently inhibited hypertrophy and Akt-dependent prohypertrophic signaling in isolated cardiac myocytes, whereas the introduction of constitutively active Akt blunted these effects of finasteride. Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice and might be a therapeutic option for heart failure. © 2015 American Heart Association, Inc.

  18. Anti-Hypertensive Drugs Have Different Effects on Ventricular Hypertrophy Regression

    Science.gov (United States)

    Filho, Celso Ferreira; de Abreu, Luiz Carlos; Valenti, Vitor E.; Ferreira, Marcelo; Meneghini, Adriano; Silveira, José Alexandre; Pérez Riera, Andrés R.; Colombari, Eduardo; Murad, Neif; Santos-Silva, Paulo Roberto; da Silva, Lovian José Henrique Pereira; Vanderlei, Luiz Carlos Marques; Carvalho, Tatiana D.; Ferreira, Celso

    2010-01-01

    OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH) and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed), Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor) and verapamil (Ca++ channel blocker) caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker) were similar. Indapamina (diuretic) had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1) receptor antagonist) produced better results than atenolol (selective β1 receptor antagonist) with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression. PMID:20668631

  19. Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

    Science.gov (United States)

    Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

    2016-12-15

    Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes.

    Science.gov (United States)

    Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

    2015-08-14

    Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

  1. Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways.

    Science.gov (United States)

    Cao, Zhen; Dou, Ce; Dong, Shiwu

    2017-01-01

    Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, it is very important to find out a suitable way to maintain the phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving from turmeric was reported with anti-inflammatory and anti-tumor pharmacological effects. However, the role of curcumin in metabolism of chondrocytes, especially in the chondrocyte hypertrophy remains unclear. Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering as seed cells. So we investigated the effect of curcumin on chondrogenesis and chondrocyte hypertrophy in MSCs through examination of cell viability, glycosaminoglycan synthesis and specific gene expression. We found curcumin had no effect on expression of chondrogenic markers including Sox9 and Col2a1 while hypertrophic markers including Runx2 and Col10a1 were down-regulated. Further exploration showed that curcumin inhibited chondrocyte hypertrophy through Indian hedgehog homolog (IHH) and Notch signalings. Our results indicated curcumin was a potential agent in modulating cartilage homeostasis and maintaining chondrocyte phenotype.

  2. Mulberry hypertrophy and accompanying sinonasal pathologies: A review of 68 cases.

    Science.gov (United States)

    Akduman, Davut; Haksever, Mehmet; Yanilmaz, Muhammed; Solmaz, Fevzi

    2016-08-01

    Mulberry hypertrophy occasionally coexists with sinonasal pathologies. There are very few reports in the literature on this clinical entity. We conducted a retrospective study to draw attention to this condition in the context of accompanying sinonasal pathologies. Our study group was made up of 68 patients-51 males and 17 females, aged 13 to 57 years (mean: 34.9)-who had been diagnosed with mulberry hypertrophy and at least one accompanying sinonasal pathology. All patients had a long-standing chronic discharge. Forty-nine of these patients (72.1%) had unilateral mulberry hypertrophy. The most common concomitant pathologies were chronic rhinosinusitis and ostiomeatal complex disease; others included septal deviation, nasal polyposis, allergic rhinitis, and concha bullosa. Thirty-six patients (52.9%) with varying degrees of choanal/nasal obstruction were operated on with endoscopic excision to treat the mulberry hypertrophy. In all, most patients underwent some sort of surgery to treat either the mulberry hypertrophy or the accompanying sinonasal pathology. Based on our findings, we suggest a clinical staging system to serve as a way to standardize management and guide future basic and clinical research.

  3. Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python bivittatus).

    Science.gov (United States)

    Slay, Christopher E; Enok, Sanne; Hicks, James W; Wang, Tobias

    2014-05-15

    Physiological cardiac hypertrophy is characterized by reversible enlargement of cardiomyocytes and changes in chamber architecture, which increase stroke volume and via augmented convective oxygen transport. Cardiac hypertrophy is known to occur in response to repeated elevations of O2 demand and/or reduced O2 supply in several species of vertebrate ectotherms, including postprandial Burmese pythons (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P. bivittatus is a facultative rather than obligatory response to digestion, though the triggers of this response are unknown. Here, we hypothesized that an O2 supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese pythons. To test this hypothesis, we rendered animals anemic prior to feeding, essentially halving blood oxygen content during the postprandial period. Fed anemic animals had heart rates 126% higher than those of fasted controls, which, coupled with a 71% increase in mean arterial pressure, suggests fed anemic animals were experiencing significantly elevated cardiac work. We found significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles 39% larger than those of fasted controls and 28% larger than in fed controls. These findings support our hypothesis that those animals with a greater magnitude of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal' stimulating postprandial cardiac hypertrophy is likely mediated by elevated ventricular wall stress associated with postprandial hemodynamics. © 2014. Published by The Company of Biologists Ltd.

  4. Role of ubiquitin-proteasome system (UPS) in left ventricular hypertrophy (LVH).

    Science.gov (United States)

    Cacciapuoti, Federico

    2014-01-01

    Cardiac hypertrophy is a key compensatory mechanism acting in response to pressure or volume overload, involving some alterations in signaling transduction pathways and transcription factors-regulation. These changes result in enhanced proteins' synthesis leading to Left Ventricular Hypertrophy (LVH). It is known that the main function of Ubiquitin-Proteasome System (UPS) is to prevent accumulation of damaged, misfolded and mutant proteins by proteolysis. But emerging evidences suggest that UPS also attends to the cells' growth, favoring proteins' synthesis, subsequently evolving in LVH. The role of the proteasome in to favor cellular hypertrophy consists in upregulation of the catalytic proteasome subunit, with prevalence of proteins-synthesis on proteins degradation. It is also evident that UPS inhibition may prevent cells' growth opposing to the hypertrophy. In fact in several experimental models, UPS inhibition demonstrated to be able to prevent or reverse cardiac hypertrophy induced by abdominal aortic banding (AAB). That can happen with several proteasome inhibitors acting by multifactorial mechanisms. These evidences induce to hypothesize that, in the future, in patients with the increased volume overload by systemic hypertension, some proteasome-inhibitors could be used to antagonize or prevent LVH without reducing peripheral high blood pressure levels too.

  5. Interleukin-6 deficiency attenuates angiotensin II-induced cardiac pathogenesis with increased myocyte hypertrophy.

    Science.gov (United States)

    Chen, Fan; Chen, Dandan; Zhang, Yubin; Jin, Liang; Zhang, Han; Wan, Miyang; Pan, Tianshu; Wang, Xiaochuan; Su, Yuheng; Xu, Yitao; Ye, Junmei

    2017-12-16

    Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 μg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro. Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Leilei Zhong

    2015-08-01

    Full Text Available Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA. Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP/Transforming growth factor-β (TGFβ, Parathyroid hormone-related peptide (PTHrP, Indian hedgehog (IHH, Fibroblast growth factor (FGF, Insulin like growth factor (IGF and Hypoxia-inducible factor (HIF. This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

  7. The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi [Gunma Prefectural Cardiovascular Center (Japan)] (and others)

    1999-09-01

    We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with {sup 123}I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting {sup 201}Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced {sup 201}Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy. (author)

  8. Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy

    Science.gov (United States)

    Bang, Claudia; Batkai, Sandor; Dangwal, Seema; Gupta, Shashi Kumar; Foinquinos, Ariana; Holzmann, Angelika; Just, Annette; Remke, Janet; Zimmer, Karina; Zeug, Andre; Ponimaskin, Evgeni; Schmiedl, Andreas; Yin, Xiaoke; Mayr, Manuel; Halder, Rashi; Fischer, Andre; Engelhardt, Stefan; Wei, Yuanyuan; Schober, Andreas; Fiedler, Jan; Thum, Thomas

    2014-01-01

    In response to stress, the heart undergoes extensive cardiac remodeling that results in cardiac fibrosis and pathological growth of cardiomyocytes (hypertrophy), which contribute to heart failure. Alterations in microRNA (miRNA) levels are associated with dysfunctional gene expression profiles associated with many cardiovascular disease conditions; however, miRNAs have emerged recently as paracrine signaling mediators. Thus, we investigated a potential paracrine miRNA crosstalk between cardiac fibroblasts and cardiomyocytes and found that cardiac fibroblasts secrete miRNA-enriched exosomes. Surprisingly, evaluation of the miRNA content of cardiac fibroblast–derived exosomes revealed a relatively high abundance of many miRNA passenger strands (“star” miRNAs), which normally undergo intracellular degradation. Using confocal imaging and coculture assays, we identified fibroblast exosomal–derived miR-21_3p (miR-21*) as a potent paracrine-acting RNA molecule that induces cardiomyocyte hypertrophy. Proteome profiling identified sorbin and SH3 domain-containing protein 2 (SORBS2) and PDZ and LIM domain 5 (PDLIM5) as miR-21* targets, and silencing SORBS2 or PDLIM5 in cardiomyocytes induced hypertrophy. Pharmacological inhibition of miR-21* in a mouse model of Ang II–induced cardiac hypertrophy attenuated pathology. These findings demonstrate that cardiac fibroblasts secrete star miRNA–enriched exosomes and identify fibroblast-derived miR-21* as a paracrine signaling mediator of cardiomyocyte hypertrophy that has potential as a therapeutic target. PMID:24743145

  9. Cardiac hypertrophy and dysfunction induced by overexpression of miR-214 in vivo.

    Science.gov (United States)

    Yang, Tao; Gu, Haihua; Chen, Xiaofan; Fu, Shaozhi; Wang, Cheng; Xu, Hongfei; Feng, Qiang; Ni, Yiming

    2014-12-01

    An increasing number of studies have demonstrated the critical role of microRNAs in the pathogenesis of cardiac hypertrophy and dysfunction. This study evaluated whether miR-214 plays a pivotal role in the development of cardiac hypertrophy and heart failure. In human tissues, miR-214 overexpression was determined to promote cardiac hypertrophy. We predicted miR-214 direct target by bioinformatics database and verifed it using luciferase dual reporting system. We silenced miR-214 using a specific antagomir in a pressure-overload mouse model of heart failure. Analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-214 indicated that their hearts were 21% heavier than wild-type hearts and expressed several biochemical and functional markers consistent with dilated cardiomyopathy. These findings include enlarged left ventricular internal diameters, wall thinning, reduced ejection fraction, fractional shortening, and an increased fetal gene expression. The enhancer of zeste homolog 2 (EZH2) was confirmed as a direct target of miR-214 in cardiomyocytes. In vivo silencing of miR-214 using a specific antagomir rescued cardiac EZH2 expression and prevented cardiac hypertrophy and dysfunction. Taken together, these results suggest that miR-214 may induce pathologic cardiac hypertrophy in part by reducing EZH2 messenger RNA levels. MiR-214 may therefore be a potential therapeutic target for treating certain cardiac disease states. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.

    Science.gov (United States)

    Prado, Fernanda P; Dos Santos, Daniele O; Blefari, Valdecir; Silva, Carlos A; Machado, Juliano; Kettelhut, Isis do Carmo; Ramos, Simone G; Baruffi, Marcelo Dias; Salgado, Helio C; Prado, Cibele M

    2017-01-01

    Hypertension causes cardiac hypertrophy, one of the most important risk factors for heart failure (HF). Despite the importance of cardiac hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations of cytoskeletal and sarcolemma-associated proteins are considered markers cardiac remodeling during HF. Dystrophin provides mechanical stability to the plasma membrane through its interactions with the actin cytoskeleton and, indirectly, to extracellular matrix proteins. This study was undertaken to evaluate dystrophin and calpain-1 in the transition from compensated cardiac hypertrophy to HF. Wistar rats were subjected to abdominal aorta constriction and killed at 30, 60 and 90 days post surgery (dps). Cardiac function and blood pressure were evaluated. The hearts were collected and Western blotting and immunofluorescence performed for dystrophin, calpain-1, alpha-fodrin and calpastatin. Statistical analyses were performed and considered significant when pcardiac disease. We showed that decreased expression of dystrophin and increased expression of calpains are coincident and could work as possible therapeutic targets to prevent heart failure as a consequence of cardiac hypertrophy.

  11. Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure.

    Science.gov (United States)

    Heger, J; Schulz, R; Euler, G

    2016-01-01

    Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed. © 2015 The British Pharmacological Society.

  12. Pivotal Role of Regulator of G-protein Signaling 12 in Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    Huang, Jia; Chen, Lijuan; Yao, Yuyu; Tang, Chengchun; Ding, Jiandong; Fu, Cong; Li, Hongliang; Ma, Genshan

    2016-06-01

    Cardiac hypertrophy is a major predictor of heart failure and is regulated by diverse signaling pathways. As a typical multi-domain member of the regulator of G-protein signaling (RGS) family, RGS12 plays a regulatory role in various signaling pathways. However, the precise effect of RGS12 on cardiac hypertrophy remains largely unknown. In this study, we observed increased expression of RGS12 in the development of pathological cardiac hypertrophy and heart failure. We then generated genetically engineered mice and neonatal rat cardiomyocytes to investigate the effects of RGS12 during this pathological process. Four weeks after aortic banding, RGS12-deficient hearts showed decreased cardiomyocyte cross area (374.7±43.2 μm(2) versus 487.1±47.9 μm(2) in controls; Phypertrophy in isolated cardiomyocytes. Mechanistically, our data indicated that the activation of MEK1/2-ERK1/2 signaling may be responsible for the prohypertrophic action of RGS12. In addition, the requirement of the MEK1/2-ERK1/2 signaling for RGS12-mediated cardiac hypertrophy was confirmed in rescue experiments using the MEK1/2-specific inhibitor U0126. In conclusion, our findings provide a novel diagnostic and therapeutic target for pathological cardiac hypertrophy and heart failure. © 2016 American Heart Association, Inc.

  13. Etanercept protects rat cardiomyocytes against hypertrophy by regulating inflammatory cytokines secretion and cell apoptosis.

    Science.gov (United States)

    Li, Q; Yu, Q; Na, R; Liu, B

    2017-05-15

    We aimed to investigate the effect of etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, on rat cardiomyocyte hypertrophy and its underlying mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and then treated with different concentrations of etanercept (1, 10, and 50 μM). After treatment, cell counts, viability and cell apoptosis were evaluated. The mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT-PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were measured by western blotting. The protein levels of transforming growth factor-β1 (TGF-β1), interleukin (IL)-1β, IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1) were determined using enzyme linked immunosorbent assay (ELISA) kits. In the present study, TNF-α level in cardiomyocytes with hypertrophy was significantly enhanced (Petanercept (Petanercept remarkably reduced the mRNA levels of ANF, MMP-9 and MMP-13, inhibited the expression of Bax, and increased the expression of Bcl-2 compared to the model group (Petanercept lowered the levels of IL-1β, IL-6, LIF and CT-1 but not TGF-β1 compared to the model group (PEtanercept may protect rat cardiomyocytes from hypertrophy by inhibiting inflammatory cytokines secretion and cell apoptosis.

  14. Ligustrazine Inhibits Cartilage Endplate Hypertrophy via Suppression of TGF-β1

    Directory of Open Access Journals (Sweden)

    Shufen Liu

    2016-01-01

    Full Text Available CEP hypertrophy is one of the characteristics of intervertebral disc degeneration (IDD. LIG exerts a protective effect on IDD in animal model. The effect of LIG on CEP hypertrophy is further investigated in the present study. Cells were isolated from hypertrophic samples obtained from patients during vertebral fusion surgery. Cellular proliferation and the expression of type I collagen (Col I and TGF-β1 were tested. In the bipedal rats, the edges of the CEP and the sizes of noncartilaginous outgrowth, as well as the expression of osteogenic markers, Col1a, ALP, Runx2, and TGF-β1, were detected. Within two passages, the condensed hypertrophic CEP cells exhibited osteogenic capacity by bony-like nodules and ALP positive staining, along with increased expression of Col I and TGF-β1. LIG inhibited proliferation of CEP cells and downregulated the expression of Col I and TGF-β1 in vitro. Furthermore, LIG attenuated CEP hypertrophy on the lumbar spine of bipedal rats by reducing Col1a, ALP, Runx2, and TGF-β1 mRNA expression and TGF-β1 distribution in vivo. We concluded LIG exerted a preventive effect on CEP hypertrophy via suppression of TGF-β1 levels. This information could be used to develop alternative therapeutic methods to treat spinal CEP hypertrophy.

  15. Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy.

    Science.gov (United States)

    Sorriento, Daniela; Santulli, Gaetano; Franco, Antonietta; Cipolletta, Ersilia; Napolitano, Luigi; Gambardella, Jessica; Gomez-Monterrey, Isabel; Campiglia, Pietro; Trimarco, Bruno; Iaccarino, Guido; Ciccarelli, Michele

    2015-11-01

    G protein coupled receptor kinase type 2 (GRK2) plays an important role in the development and maintenance of cardiac hypertrophy and heart failure even if its exact role is still unknown. In this study, we assessed the effect of GRK2 on the regulation of cardiac hypertrophy. In H9C2 cells, GRK2 overexpression increased atrial natriuretic factor (ANF) activity and enhanced phenylephrine-induced ANF response, and this is associated with an increase of NFκB transcriptional activity. The kinase dead mutant and a synthetic inhibitor of GRK2 activity exerted the opposite effect, suggesting that GRK2 regulates hypertrophy through upregulation of NFκB activity in a phosphorylation-dependent manner. In two different in vivo models of left ventricle hypertrophy (LVH), the selective inhibition of GRK2 activity prevented hypertrophy and reduced NFκB transcription activity. Our results suggest a previously undisclosed role for GRK2 in the regulation of hypertrophic responses and propose GRK2 as potential therapeutic target for limiting LVH.

  16. Urocortin-induced cardiomyocytes hypertrophy is associated with regulation of the GSK-3β pathway.

    Science.gov (United States)

    Gruson, Damien; Ginion, Audrey; Decroly, Noémie; Lause, Pascale; Vanoverschelde, Jean-Louis; Ketelslegers, Jean-Marie; Bertrand, Luc; Thissen, Jean-Paul

    2012-03-01

    Urocortin-1 (UCN), a member of the corticotropin-releasing factor, is a cardioprotective peptide, and is also involved in cardiac hypertrophy. The involvement of GSK-3β, a pivotal kinase in cardiac hypertrophy, in response to UCN is not yet documented. Cardiomyocytes from adult rats were stimulated for 48 h with UCN. Cell size, protein, and DNA contents were determined. Phosphorylated and total forms GSK-3β and the total amount of β-catenin were quantified by Western immunoblots. The effects of astressin, a UCN competitive receptor antagonist, were also evaluated. UCN increased cell size and the protein-to-DNA ratio, in accordance with a hypertrophic response. This effect was associated with increased phosphorylation of GSK-3β and marked accumulation of β-catenin, a downstream element to GSK-3β. All these effects were prevented by astressin and LY294002, an inhibitor of the phosphatidyl-inositol-3-kinase. UCN-induced cardiomyocytes hypertrophy is associated with regulation of GSK-3β, a pivotal kinase involved in cardiac hypertrophy, in a PI3K-dependent manner. Furthermore, the pharmacological blockade of UCN receptors was able to prevent UCN-induced hypertrophy, which leads to inhibition of the Akt/GSK-3β pathway.

  17. Myocardial Structural and Biological Anomalies Induced by High Fat Diet in Psammomys obesus Gerbils.

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    Abdelhamid Sahraoui

    Full Text Available Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils.Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels were evaluated. Myocardial samples were collected for pathobiological evaluation.Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL-1β and tumor necrosis factor (TNF-α], intercellular (ICAM1 and vascular adhesion molecules (VCAM1 increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6, was downregulated. Myocardial expressions of sarco(endoplasmic calcium-ATPase (SERCA2 and voltage-dependent calcium channel (Cacna1c decreased, while protein kinase A (PKA and calcium-calmodulin-dependent protein kinase (CaMK2D expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1 did not change.We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants.

  18. Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat.

    Science.gov (United States)

    Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

    2015-01-01

    This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (pcholesterol level tended to increase and hepatic total cholesterol level decreased and were comparable to the CON group (p>0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (pcholesterol level, kidney, and body fat weights decreased, and were compared to the CON group (p>0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat.

  19. Dietary Fats and Metabolic Syndrome

    OpenAIRE

    Danijela Ristic-Medic

    2013-01-01

    The quantity and quality of fats consumed in the diet can have important effects on prevention and/or improvement clustering metabolic abnormalities of the metabolic syndrome. Fatty acids as food ingredients regulate cholesterol homeostasis and concentrations of blood lipoproteins, and affect the levels of other cardiometabolic risk factors, such as blood pressure, haemostasis, and body weight, through various mechanisms. There is convincing evidence that exchanging dietary saturated fat with...

  20. Cardiac Biomarkers and Left Ventricular Hypertrophy in Asymptomatic Hemodialysis Patients

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    Reneta Yovcheva Koycheva

    2015-12-01

    Full Text Available BACKGROUND: Cardiac biomarkers are often elevated in dialysis patients showing the presence of left ventricular dysfunction. The aim of the study is to establish the plasma levels of high-sensitivity cardiac troponin T (hs TnT, precursor of B-natriuretic peptide (NT-proBNP and high sensitivity C-reactive protein (hs CRP and their relation to the presence of left ventricular hypertrophy (LVH in patients undergoing hemodialysis without signs of acute coronary syndrome or heart failure. MATERIAL AND METHODS: Were studied 48 patients - 26 men and 22 women. Pre and postdialysis levels of hs cTnT, NT-proBNP and hs CRP were measured at week interim procedure. Patients were divided in two groups according to the presence of echocardiographic evidence of LVH - gr A - 40 patients (with LVH, and gr B - 8 patients (without LVH. RESULTS: In the whole group of patients was found elevated predialysis levels of all three biomarkers with significant increase (p < 0.05 after dialysis with low-flux dialyzers. Predialysis values of NT-proBNP show moderate positive correlation with hs cTnT (r = 0.47 and weaker with hs CRP (r = 0.163. Such dependence is observed in postdialysis values of these biomarkers. There is a strong positive correlation between the pre and postdialysis levels: for hs cTnT (r = 0.966, for NT-proBNP (r = 0.918 and for hs CRP (r = 0.859. It was found a significant difference in the mean values of hs cTnT in gr. A and gr. B (0.07 ± 0.01 versus 0.03 ± 0.01 ng /mL, p < 0.05 and NT-proBNP (15,605.8 ± 2,072.5 versus 2,745.5 ± 533.55 pg /mL, p < 0.05. Not find a significant difference in hs CRP in both groups. CONCLUSIONS: The results indicate the relationship of the studied cardiac biomarkers with LVH in asymptomatic patients undergoing hemodialysis treatment.

  1. Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor

    Directory of Open Access Journals (Sweden)

    Eric E. Essick

    2011-01-01

    Full Text Available Obesity and hypertension, major risk factors for the metabolic syndrome, render individuals susceptible to an increased risk of cardiovascular complications, such as adverse cardiac remodeling and heart failure. There has been much investigation into the role that an increase in the renin-angiotensin-aldosterone system (RAAS plays in the pathogenesis of metabolic syndrome and in particular, how aldosterone mediates left ventricular hypertrophy and increased cardiac fibrosis via its interaction with the mineralocorticoid receptor (MR. Here, we review the pertinent findings that link obesity with elevated aldosterone and the development of cardiac hypertrophy and fibrosis associated with the metabolic syndrome. These studies illustrate a complex cross-talk between adipose tissue, the heart, and the adrenal cortex. Furthermore, we discuss findings from our laboratory that suggest that cardiac hypertrophy and fibrosis in the metabolic syndrome may involve cross-talk between aldosterone and adipokines (such as adiponectin.

  2. Radiofrequency Coblation Versus Intramural Bipolar Cautery for the Treatment of Inferior Turbinate Hypertrophy.

    Science.gov (United States)

    Shah, Anil N; Brewster, Douglas; Mitzen, Kelly; Mullin, David

    2015-09-01

    Compare intramural bipolar electrocautery and radiofrequency coblation in the treatment of inferior turbinate hypertrophy with regards to objective and subjective improvement in nasal obstruction, rate and type of complications, experience during the procedure, and rate of recovery. Prospective, single-blinded study. Single tertiary medical center from 2008 to 2010. Forty-one adult patients with inferior turbinate hypertrophy refractory to medical management were treated with radiofrequency coblation in one nostril and intramural bipolar cautery in the other. Subjective and objective data, including use of a Visual Analog Scale (VAS) for subjective outcomes, acoustic rhinometry, and nasal endoscopy, were then obtained from each patient comparing the 2 techniques. Radiofrequency coblation was significantly less painful than intramural bipolar cautery during the procedure (P = .03) and during the early postoperative period (P hypertrophy with less discomfort during the procedure and early post-operative period. © The Author(s) 2015.

  3. Atrial natriuretic factor gene expression in ventricles of rats with spontaneous biventricular hypertrophy.

    Science.gov (United States)

    Lee, R T; Bloch, K D; Pfeffer, J M; Pfeffer, M A; Neer, E J; Seidman, C E

    1988-02-01

    A subset of Wistar-Kyoto (WKY) rats that spontaneously develops biventricular hypertrophy (BVH) in response to increased cardiac output was evaluated for ventricular expression of the atrial natriuretic factor (ANF) gene. Normal WKY rats had low levels of left ventricular ANF mRNA and minimally detectable ANF transcripts in the right ventricle. In contrast, BVH rats showed a sixfold greater ANF mRNA concentration in the left ventricle than age-matched WKY controls. BVH right ventricular ANF mRNA levels equaled those found in BVH left ventricles and were dramatically greater than WKY right ventricular controls. Unlike experimental models of hypertrophy, both left and right ventricles significantly increase ANF gene transcripts in the natural development of BVH. The left and right ventricles can concordantly respond to hypertrophy and increase ANF gene transcription.

  4. Unilateral hypertrophy of tensor fascia lata: a soft tissue tumor simulator

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, H. [Department of Radiology, Mayo Clinic, 200 First Street, 55905, SW Rochester, MN (United States); Department of Radiology A21, Cleveland Clinic, Cleveland, OH (United States); Wenger, D.E. [Department of Radiology, Mayo Clinic, 200 First Street, 55905, SW Rochester, MN (United States); Shives, T.C. [Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN (United States); Unni, K.K. [Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (United States)

    2003-11-01

    To describe the imaging findings in eight cases of unilateral tensor fascia lata (TFL) hypertrophy presenting as soft tissue masses. Imaging studies and medical charts of eight patients were reviewed retrospectively. The imaging studies included five radiographs, five computed tomography (CT) and six magnetic resonance imaging (MRI) examinations. The majority of patients (seven of eight) presented with a palpable proximal anterior thigh mass. One patient was asymptomatic and incidentally diagnosed. There were six females and two males. Ages ranged from 27 to 86 years old (mean 61). MRI and CT showed unilateral enlargement of the TFL muscle in all cases. TFL muscle hypertrophy is an uncommon clinical entity, which can simulate a soft tissue tumor. The characteristic appearance on CT or MRI allows a confident diagnosis of muscle hypertrophy to be made, avoiding unnecessary biopsy or surgical intervention. (orig.)

  5. Pharmacological interference of vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin.

    Science.gov (United States)

    Peiró, C; Vallejo, S; Nevado, J; Angulo, J; Llergo, J L; Cercas, E; Rodríguez-Mañas, L; Sánchez-Ferrer, C F

    1999-12-15

    Nonenzymatically glycosylated human oxyhaemoglobin induces vascular smooth muscle cell hypertrophy by releasing reactive oxygen species. We analysed the ability of drugs with antihypertrophic properties for the vascular wall and/or antioxidant activity, such as captopril, losartan, and nifedipine, or gliclazide, carvedilol, and ascorbic acid, to interfere with 10 nM glycosylated human oxyhaemoglobin-induced increase in vascular smooth muscle cell size (118+/-0.5% of basal). Vascular smooth muscle cell hypertrophy was abolished concentration-dependently, with pD(2) values over a 100-fold interval: 6.4+/-0.3, 7.7+/-0.4, 7.3+/-0.4, 7.4+/-0.6, 8. 8+/-0.2, and 9.0+/-0.2 for captopril, losartan, nifedipine, ascorbic acid, carvedilol and gliclazide, respectively. Drugs with powerful antioxidant properties, especially carvedilol and gliclazide, are particularly effective in preventing glycosylated human oxyhaemoglobin-induced vascular smooth muscle cell hypertrophy.

  6. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy

    DEFF Research Database (Denmark)

    Hinrichsen, R.; Hansen, A.H.; Busk, P.K.

    2008-01-01

    OBJECTIVES: A number of stimuli induce cardiac hypertrophy and may lead to cardiomyopathy and heart failure. It is believed that cardiomyocytes withdraw from the cell cycle shortly after birth and become terminally differentiated. However, cell cycle regulatory proteins take part in the development...... of hypertrophy, and it is important to elucidate the mechanisms of how these proteins are involved in the hypertrophic response in cardiomyocytes. MATERIALS AND METHODS, AND RESULTS: In the present study, by immunohistochemistry with a phosphorylation-specific antibody, we found that cyclin D-cdk4....../6-phosphorylated retinoblastoma protein (pRb) during hypertrophy and expression of an unphosphorylatable pRb mutant impaired hypertrophic growth in cardiomyocytes. Transcription factor E2F was activated by hypertrophic elicitors but activation was impaired by pharmacological inhibition of cyclin D-cdk4...

  7. Essential role of STIM1 in the development of cardiomyocyte hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ohba, Takayoshi [Department of Physiology, Akita University Graduate School of Medicine, Akita (Japan); Watanabe, Hiroyuki [Department of Internal Medicine Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, Akita (Japan); Murakami, Manabu [Department of Physiology, Akita University Graduate School of Medicine, Akita (Japan); Sato, Takako [Department of Internal Medicine Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, Akita (Japan); Ono, Kyoichi [Department of Physiology, Akita University Graduate School of Medicine, Akita (Japan); Ito, Hiroshi, E-mail: hitomed2@gipc.akita-u.ac.jp [Department of Internal Medicine Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, Akita (Japan)

    2009-11-06

    Store-operated Ca{sup 2+} entry (SOCE) through transient receptor potential (TRP) channels is important in the development of cardiac hypertrophy. Recently, stromal interaction molecule 1 (STIM1) was identified as a key regulator of SOCE. In this study, we examined whether STIM1 is involved in the development of cardiomyocyte hypertrophy. RT-PCR showed that cultured rat cardiomyocytes constitutively expressed STIM1. Endothelin-1 (ET-1) treatment for 48 h enhanced TRPC1 expression, SOCE, and nuclear factor of activated T cells activation without upregulating STIM1. However, the knockdown of STIM1 suppressed these effects, thereby preventing a hypertrophic response. These results suggest that STIM1 plays an essential role in the development of cardiomyocyte hypertrophy.

  8. The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy

    Science.gov (United States)

    Mohamed, Tamer M. A.; Abou-Leisa, Riham; Stafford, Nicholas; Maqsood, Arfa; Zi, Min; Prehar, Sukhpal; Baudoin-Stanley, Florence; Wang, Xin; Neyses, Ludwig; Cartwright, Elizabeth J.; Oceandy, Delvac

    2016-01-01

    The heart responds to pathological overload through myocyte hypertrophy. Here we show that this response is regulated by cardiac fibroblasts via a paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). Pmca4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out Pmca4 specifically in cardiomyocytes does not produce this effect. Mechanistically, cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes. Furthermore, we show that treatment with the PMCA4 inhibitor aurintricarboxylic acid (ATA) inhibits and reverses cardiac hypertrophy induced by pressure overload in mice. Our results reveal that PMCA4 regulates the development of cardiac hypertrophy and provide proof of principle for a therapeutic approach to treat this condition. PMID:27020607

  9. Identification of genes regulated during mechanical load-induced cardiac hypertrophy

    Science.gov (United States)

    Johnatty, S. E.; Dyck, J. R.; Michael, L. H.; Olson, E. N.; Abdellatif, M.; Schneider, M. (Principal Investigator)

    2000-01-01

    Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

  10. Frequent left ventricular hypertrophy independent of blood pressure in 1851 pre-western Inuit

    DEFF Research Database (Denmark)

    Andersen, Stig; Kjærgaard, Marie; Jørgensen, Marit Eika

    2011-01-01

    BACKGROUND: Elevated blood pressure is a risk factor for cardiovascular disease and may be detected by left ventricular hypertrophy (LVH) in electrocardiogram (ECG). Pre-western Inuit had frequent signs of LVH in ECG predominantly in the 3rd decade while a low occurrence of ischemic heart disease....... METHODS: We evaluated the association between blood pressures and ECG signs of LVH, cardiac auscultation, and symptoms related to heart disease in the recently recovered data from the survey of 1851 Inuit conducted in 1962-1964 in East Greenland. RESULTS: The participation rate was 97%. Among the 812...... only after the age of 40 years in pre-western Inuit. Left ventricular hypertrophy peaked among 30-year olds and was independent of elevated blood pressure. It may be speculated that the common left ventricular hypertrophy was due to marked physical activity that contributed to the low occurrence...

  11. PEG-coated gold nanoparticles attenuate β-adrenergic receptor-mediated cardiac hypertrophy.

    Science.gov (United States)

    Qiao, Yuhui; Zhu, Baoling; Tian, Aiju; Li, Zijian

    2017-01-01

    Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can accumulate in the heart through blood circulation. Therefore, it is very important to understand the effect of AuNPs on the heart, especially under pathological conditions. In this study, we found that PEG-coated AuNPs attenuate β-adrenergic receptor (β-AR)-mediated acute cardiac hypertrophy and inflammation. However, both isoproterenol, a non-selective β-AR agonist, and AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted an anti-cardiac hypertrophy effect by decreasing β 1 -AR expression and its downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be safe and have the potential to be used as multi-functional materials (drug carrier systems and anti-cardiac hypertrophy agents).

  12. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  13. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2.

    Science.gov (United States)

    Witting, N; Duno, M; Vissing, J

    2013-01-01

    Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. What Are the Types of Fat?

    Science.gov (United States)

    ... N09 Version 5.0 Page 2 of 3 Harmful Dietary Fats Saturated Fat High-fat cuts of meat (beef, lamb, pork) Chicken with the skin Whole-fat dairy products (cream/milk) Butter Palm and coconut oil (snack foods, non- ...

  15. Tumor Suppressor A20 Protects against Cardiac Hypertrophy and Fibrosis through Blocking TAK1-Dependent Signaling

    Science.gov (United States)

    Huang, He; Tang, Qi-Zhu; Wang, Ai-Bing; Chen, Manyin; Zhou, Heng; Liu, Chen; Jiang, Hong; Yang, Qinglin; Bian, Zhou-Yan; Bai, Xue; Zhu, Li-Hua; Wang, Lang; Li, Hongliang

    2010-01-01

    A20 or tumor necrosis factor–induced protein 3 is a negative regulator of nuclear factor κB signaling. A20 has been shown previously to attenuate cardiac hypertrophy in vitro and postmyocardial infarction remodeling in vivo. In the present study, we tested the hypothesis that overexpression of A20 in the murine heart would protect against cardiac hypertrophy in vivo. The effects of constitutive human A20 expression on cardiac hypertrophy were investigated using in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding in A20 transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by echocardiography, as well as by pathological and molecular analyses of heart samples. Constitutive overexpression of human A20 in the murine heart attenuated the hypertrophicresponse and markedly reduced inflammation, apoptosis, and fibrosis. Cardiac function was also preserved in hearts with increased A20 levels in response to hypertrophic stimuli. Western blot experiments further showed A20 expression markedly blocked transforming growth factor-β–activated kinase 1–dependent c-Jun N-terminal kinase/p38 signaling cascade but with no difference in either extracellular signal-regulated kinase 1/2 or AKT activation in vivo and in vitro. In cultured neonatal rat cardiac myocytes, [3H]proline incorporation and Western blot assays revealed that A20 expression suppressed transforming growth factor-β–induced collagen synthesis and transforming growth factor-β–activated kinase 1–dependent Smad 2/3/4 activation. In conclusion, A20 improves cardiac functions and inhibits cardiac hypertrophy, inflammation, apoptosis, and fibrosis by blocking transforming growth factor-β–activated kinase 1–dependent signaling. PMID:20585109

  16. Effect of Nigella sativa supplementation to exercise training in a novel model of physiological cardiac hypertrophy.

    Science.gov (United States)

    Al-Asoom, L I; Al-Shaikh, B A; Bamosa, A O; El-Bahai, M N

    2014-09-01

    Exercise training is employed as supplementary therapy to patients with heart failure due to its multiple beneficial cardiac effects including physiological remodeling of the heart. However, precautions might be taken for the concomitant high oxidant release. Nigella sativa (NS) has been found to induce cardiac hypertrophy and enhance cardiac function. Combination of NS supplementation and exercise training might induce a safer model of cardiac hypertrophy. Our aim was to study biomarkers associated with cardiac hypertrophy induced by NS supplementation of exercise-trained rats. Forty-five adult male Wistar rats (body weight 150-220 g) were divided equally into three groups: control, exercise-trained (ET) and NS-treated-exercise-trained (NSET) groups. Daily 800 mg/kg NS was administered orally to NSET group for 8 weeks. Rats of the ET and NSET groups were subjected to treadmill running sessions for 2 h/day for 8 weeks. By the end of the experiment, the following were recorded: body, heart and left ventricular weights (BW, HW, LVW), cardiomyocyte diameter, serum growth hormone, insulin growth factor-I (IGF-I), thyroid hormones, catecholamines, total nitrate, ICAM and antioxidant capacity. A homogenous cardiac hypertrophy was evidenced by increased HW/BW, LVW/BW ratios and cardiomyocyte diameter in the two groups of exercise-trained compared with control rats. Rats of ET group had higher growth hormone. Those of NSET group developed higher IGF-I and total antioxidant capacity, as well as lower serum thyroxin level. Simultaneous NS supplementation to an exercise training program preserves and augments exercise-induced physiological cardiac hypertrophy with step-forward adaptive signs of increased IGF-I and reduced thyroxin level, and with an added advantage of elevation of total serum antioxidant capacity. Thus, the novel model of NSET-induced cardiac hypertrophy might be introduced as a new therapeutic strategy for the treatment of heart failure with superior

  17. The effect of protein timing on muscle strength and hypertrophy: a meta-analysis.

    Science.gov (United States)

    Schoenfeld, Brad Jon; Aragon, Alan Albert; Krieger, James W

    2013-12-03

    Protein timing is a popular dietary strategy designed to optimize the adaptive response to exercise. The strategy involves consuming protein in and around a training session in an effort to facilitate muscular repair and remodeling, and thereby enhance post-exercise strength- and hypertrophy-related adaptations. Despite the apparent biological plausibility of the strategy, however, the effectiveness of protein timing in chronic training studies has been decidedly mixed. The purpose of this paper therefore was to conduct a multi-level meta-regression of randomized controlled trials to determine whether protein timing is a viable strategy for enhancing post-exercise muscular adaptations. The strength analysis comprised 478 subjects and 96 ESs, nested within 41 treatment or control groups and 20 studies. The hypertrophy analysis comprised 525 subjects and 132 ESs, nested with 47 treatment or control groups and 23 studies. A simple pooled analysis of protein timing without controlling for covariates showed a small to moderate effect on muscle hypertrophy with no significant effect found on muscle strength. In the full meta-regression model controlling for all covariates, however, no significant differences were found between treatment and control for strength or hypertrophy. The reduced model was not significantly different from the full model for either strength or hypertrophy. With respect to hypertrophy, total protein intake was the strongest predictor of ES magnitude. These results refute the commonly held belief that the timing of protein intake in and around a training session is critical to muscular adaptations and indicate that consuming adequate protein in combination with resistance exercise is the key factor for maximizing muscle protein accretion.

  18. Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy.

    Science.gov (United States)

    Moc, Courtney; Taylor, Amy E; Chesini, Gino P; Zambrano, Cristina M; Barlow, Melissa S; Zhang, Xiaoxue; Gustafsson, Åsa B; Purcell, Nicole H

    2015-02-01

    To examine the role of physiological Akt signalling in pathological hypertrophy through analysis of PHLPP1 (PH domain leucine-rich repeat protein phosphatase) knock-out (KO) mice. To investigate the in vivo requirement for 'physiological' control of Akt activation in cardiac growth, we examined the effect of deleting the Akt phosphatase, PHLPP, on the induction of cardiac hypertrophy. Basal Akt phosphorylation increased nearly two-fold in the cardiomyocytes from PHLPP1 KO mice and physiological hypertrophy induced by swimming exercise was accentuated as assessed by increased heart size and myocyte cell area. In contrast, the development of pathophysiological hypertrophy induced by pressure overload and assessed by increases in heart size, myocyte cell area, and hypertrophic gene expression was attenuated. This attenuation coincided with decreased fibrosis and cell death in the KO mice. Cast moulding revealed increased capillary density basally in the KO hearts, which was further elevated relative to wild-type mouse hearts in response to pressure overload. In vitro studies with isolated myocytes in co-culture also demonstrated that PHLPP1 deletion in cardiomyocytes can enhance endothelial tube formation. Expression of the pro-angiogenic factor VEGF was also elevated basally and accentuated in response to transverse aortic constriction in hearts from KO mice. Our data suggest that enhancing Akt activity by inhibiting its PHLPP1-mediated dephosphorylation promotes processes associated with physiological hypertrophy that may be beneficial in attenuating the development of pathological hypertrophy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  19. Polyamine Depletion Attenuates Isoproterenol-Induced Hypertrophy and Endoplasmic Reticulum Stress in Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Yan Lin

    2014-10-01

    Full Text Available Background/Aim: Polyamines (putrescine, spermidine and spermine play an essential role in cell growth, differentiation and apoptosis. Hypertrophy is accompanied by an increase in polyamine synthesis and endoplasmic reticulum stress (ERS in cardiomyocytes. The present study was undertaken to elucidate the molecular interactions between polyamines, ERS and cardiac hypertrophy. Methods: Myocardial hypertrophy was simulated by incubating cultured neonatal rat cardiomyocytes in 100 nM isoproterenol (ISO. Polyamine deletion was achieved using 0.5 mM difluoromethylornithine (DFMO. Hypertrophy was estimated using cell surface area measurements, total protein concentrations and atrial natriuretic peptide (ANP gene expression. Apoptosis was measured using flow cytometry and transmission electron microscopy. Expression of ornithine decarboxylase (ODC and spermidine/spermine N1-acetyltransferase (SSAT were analyzed via real-time PCR and Western blotting. Protein expression of ERS and apoptosis factors were analyzed using Western blotting. Results: DFMO (0.5 mM and 2 mM treatments significantly attenuated hypertrophy and apoptosis induced by ISO in cardiomyocytes. DFMO also decreased lactate dehydrogenase (LDH and malondialdehyde (MDA level in the culture medium. In addition, DFMO (0.5 mM down regulated the expression of ODC, glucose-regulated protein 78 (GRP78, C/EBP homologous protein (CHOP, cleaved caspase-12, and Bax and up regulated the expression of SSAT and Bcl-2. Finally, these changes were partly reversed by the addition of exogenous putrescine (0.5 mM. Conclusion: The data presented here suggest that polyamine depletion could inhibit cardiac hypertrophy and apoptosis, which is closely related to the ERS pathway.

  20. The histone acetyltransferase MOF overexpression blunts cardiac hypertrophy by targeting ROS in mice.

    Science.gov (United States)

    Qiao, Weiwei; Zhang, Weili; Gai, Yusheng; Zhao, Lan; Fan, Juexin

    2014-06-13

    Imbalance between histone acetylation/deacetylation critically participates in the expression of hypertrophic fetal genes and development of cardiac hypertrophy. While histone deacetylases play dual roles in hypertrophy, current evidence reveals that histone acetyltransferase such as p300 and PCAF act as pro-hypertrophic factors. However, it remains elusive whether some histone acetyltransferases can prevent the development of hypertrophy. Males absent on the first (MOF) is a histone acetyltransferase belonging to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. Here in this study, we reported that MOF expression was down-regulated in failing human hearts and hypertrophic murine hearts at protein and mRNA levels. To evaluate the roles of MOF in cardiac hypertrophy, we generated cardiac-specific MOF transgenic mice. MOF transgenic mice did not show any differences from their wide-type littermates at baseline. However, cardiac-specific MOF overexpression protected mice from transverse aortic constriction (TAC)-induced cardiac hypertrophy, with reduced radios of heart weight (HW)/body weight (BW), lung weight/BW and HW/tibia length, decreased left ventricular wall thickness and increased fractional shortening. We also observed lower expression of hypertrophic fetal genes in TAC-challenged MOF transgenic mice compared with that of wide-type mice. Mechanically, MOF overexpression increased the expression of Catalase and MnSOD, which blocked TAC-induced ROS and ROS downstream c-Raf-MEK-ERK pathway that promotes hypertrophy. Taken together, our findings identify a novel anti-hypertrophic role of MOF, and MOF is the first reported anti-hypertrophic histone acetyltransferase. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

    Science.gov (United States)

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

    2015-01-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  2. Distribution of Hypertrophy and Late Gadolinium Enhancement in Children and Adolescents with Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Windram, Jonathan D; Benson, Lee N; Dragelescu, Andreea; Yoo, Shi-Joon; Mertens, Luc; Wong, Derek; Grosse-Wortmann, Lars

    2015-01-01

    While well characterized in adult patients, the pattern of hypertrophy and the extent of myocardial scarring in hypertrophic cardiomyopathy (HCM) are insufficiently known. The aim of this study was to assess the hypertrophy patterns and the prevalence and clinical significance of scars in the hearts of young patients with HCM. A retrospective analysis of the imaging findings of 38 children (aged 12.83 ± 2 years, 30 males) with HCM who underwent cardiac magnetic resonance imaging (CMR) was performed. In addition to left ventricular mass and volumes, the examinations were assessed for the pattern of hypertrophy and presence of late gadolinium enhancement (LGE). A myocardial signal intensity ≥6 standard deviations above the mean of normal myocardium defined positive LGE. Left ventricular mass index averaged 110 ± 34 g/m(2) . Nineteen children (50%) had diffuse septal, 13 (34%) diffuse concentric and 6 (16%) isolated basal hypertrophy. Seven children (18%) had LGE. Patients with LGE had a greater left ventricular mass index than those without (136 ± 34 g/m(2) vs. 104 ± 31 g/m(2) , P = .025). The only two patients who presented with an episode of aborted sudden cardiac death had LGE (P = .03). The most common hypertrophy pattern in children with HCM was diffuse septal hypertrophy. The incidence of LGE observed is lower than that reported in adults. The presence of LGE appears to confer a risk for adverse events. © 2015 Wiley Periodicals, Inc.

  3. Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

    Science.gov (United States)

    Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

    2016-12-01

    Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights

  4. Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy.

    Science.gov (United States)

    Ames, E G; Lawson, M J; Mackey, A J; Holmes, J W

    2013-09-01

    Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (Phypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

    Science.gov (United States)

    Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

    2017-01-01

    Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

  6. C-C Motif Chemokine Receptor 9 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

    Science.gov (United States)

    Xu, Zhengxi; Mei, Fanghua; Liu, Hanning; Sun, Cheng; Zheng, Zhe

    2016-05-04

    Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide. C-C motif chemokine receptor 9 (CCR9), a subfamily of the G protein-coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune-related diseases. Recently, CCR9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that CCR9 exerts in cardiac hypertrophy remain elusive. We observed significantly increased CCR9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss- and gain-of-function experiments, we found that pressure overload-induced hypertrophy was greatly attenuated by CCR9 deficiency in cardiac-specific CCR9 knockout mice, whereas CCR9 overexpression in cardiac-specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of CCR9 were also tested in vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for CCR9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen-activated protein kinases between groups, whereas the phosphorylation of AKT/protein kinase B and downstream effectors significantly decreased in CCR9 knockout mice and increased in CCR9 transgenic mice after aortic binding surgery. The prohypertrophic effects of CCR9 were not attributable to the mitogen-activated protein kinase signaling pathway but rather to the AKT-mammalian target of rapamycin-glycogen synthase kinase 3β signaling cascade. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. The association of residential mold exposure and adenotonsillar hypertrophy in children living in damp environments.

    Science.gov (United States)

    Atan Sahin, Ozlem; Kececioglu, Nuray; Serdar, Muhittin; Ozpinar, Aysel

    2016-09-01

    There are many consequences of mold exposure related to respiratory system health of children This retrospective cohort study aims to find the association between adenoid hypertrophy and mold exposure in children living in damp environments. Children with history of recurrent respiratory tract infections were enrolled in the study between June 2012 and June 2013 and were followed up for adenoid hypertrophy from June 2013 to June 2016. One hundred and forty two children were residents of moldy houses and 242 were living in normal houses. Skin prick test results for 60 common allergens, vitamin D levels, IgE levels, age, presence of comorbidities such as urticaria, atopic dermatitis, allergic conjunctivitis, allergic rhinitis, asthma, frequency of upper respiratory tract infections and lower respiratory tract infections, were evaluated in both groups. A total of 384 children (mean age ± standard deviation = 53.37 ± 36 months; 198 males and 186 females) were included. The children were classified into 2 groups (1)Children living normal houses (n = 242) (2); Children living in damp houses (n = 142) according to mold exposure. Children with adenoid hypertrophy (p children with mold exposure (p children with recurrent lower respiratory tract infection and upper respiratory tract infection were mainly residents of damp houses (p environment group (p Children with mold exposure had significantly increased adenoid hypertrophy regardless of their atopic nature, however, they may have become more sensitized due to other environmental triggers and genetic factors. In damp environments, sensitization to dermatophagoids, was significantly increased in children with adenoid hypertrophy. During the period of infancy, when children were mostly vitamin D supplemented, they were not sensitized and had normal adenoids. As children with recurrent respiratory tract infections grow, they tend to have lower vitamin D levels, become more atopic and tend to have adenoid

  8. Inflammation, Left Ventricular Hypertrophy, and Mortality in End-stage Renal Disease.

    Science.gov (United States)

    Cafka, Majlinda; Rroji, Merita; Seferi, Saimir; Barbullushi, Myftar; Burazeri, Genc; Spahia, Nereida; Idrizi, Alma; Likaj, Erjola; Seiti, Joana; Lazaj, Jonida; Goda, Artan

    2016-07-01

    The aim of this study was to evaluate ventricular geometry, its relationship with the inflammatory markers, and mortality of patients with end-stage renal disease on peritoneal and hemodialysis treatment. We enrolled adult patients on long-term dialysis (hemodialysis and peritoneal dialysis) for more than 3 months. Two-dimensional echocardiography was performed by an experienced cardiologist who was blinded to all clinical details of patients. Cardiovascular mortality was assessed during a 2-year follow-up period. There were 129 participants, of whom 86 (66%) were on hemodialysis. Left ventricular hypertrophy was present in 86.7%; concentric hypertrophy was found in 64 (49.1%) and eccentric hypertrophy in 48 patients (37.2%). Patients with left ventricular hypertrophy were further divided into tertiles according to their left ventricular mass index. Logistic regression found pulse pressure as an independent risk factor associated with left ventricular mass index (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.01 to 1.19; P = .047). Cardiovascular mortality rate was 15.5%. Multivariable analysis showed that C-reactive protein (OR, 1.06; 95% CI, 1.01 to 1.10; P = .01), pulse pressure (OR, 1.01; 95% CI, 1.0 to 1.26; P = .046), and left ventricular mass index (OR, 1.03; 95% CI, 1.01 to 1.21; P = .03) were independent risk factors for cardiovascular mortality. Concentric hypertrophy is the most frequent left ventricular geometry model in patients with chronic kidney disease. Inflammation, pulse pressure, and  left ventricular hypertrophy are interrelated and all contribute to mortality and cardiovascular death risk among dialysis patients.

  9. Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

    Science.gov (United States)

    Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

    2015-02-01

    Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

  10. Composition and Microstructure of Commercial Full-Fat and Low-Fat Cheeses

    OpenAIRE

    Mistry, V. V.; Anderson, D. L.

    1993-01-01

    The objective of this study was to analyze the composition of commercial full-fat and low-fat cheeses and to evaluate their microstructure. Commercial cheeses evaluated included full-fat and low-fat Cheddar, Mozzarella , processed, and Swiss cheeses. Cheddar cheeses ranged from 8.2% fat and 5 1.1% moisture in the 75% low-fat product to 33.2% fat and 35.9% moisture in the full-fat cheese . Mozzarella cheeses ranged in fat from a low of 2. I% to a high of 24% with corresponding moisture content...

  11. The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy

    DEFF Research Database (Denmark)

    Bacharova, Ljuba; Estes, Harvey E; Schocken, Douglas D

    2016-01-01

    The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended...... that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed....

  12. Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Nielsen, F S

    2005-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2...... h. RESULTS: The prevalence of LVH indexed to height(2.7) was 43% (95%CI 38-50%), and was similar in men and women. BMI, HbA(1c) and log urinary albumin excretion were significantly associated with left ventricular hypertrophy in a logistic regression model, whereas sex, age, known duration...

  13. Compensatory hypertrophy of the residual small intestine after partial enterectomy. A neurohumoral feedback?

    Science.gov (United States)

    Laplace, J P

    1980-01-01

    Experiments were designed to test, using 76 pigs, 1) whether a humoral factor inducing compensatory hypertrophy is released after partial enterectomy or not, and 2) whether visceral sensitivity conducted to the central nervous system by the route of the vagus plays a role in the compensatory hypertrophy or not. Vascular parabiosis was established between pigs paired for an identical blood group and histocompatibility. A continuous blood cross circulation was maintained for 410 h either between two normal pigs or between a normal and a jejunectomized (30 per cent) pig. Their growth and food intake, and the tissue weight of their small intestine were checked. Both the jejunectomized pigs and their unoperated partners showed a significant hypertrophy of the small intestine, whether residual or intact, as compared to intact pigs cross circulated between them. The hypertrophy observed in the unoperated partners of the jejunectomized pigs was not the result of any hyperphagia. There was thus a true humoral mediation of the compensatory hypertrophy. Vagal deafferentation, i.e. a selective surgical suppression of the vagal afferent (sensory) pathways originating below the diaphragm, was performed in jejunectomized pigs. Their performances and small intestine morphology (whole tissue weight and dry weight of the mucosa) were compared to those measured in jejunectomized but vagally intact pigs. The dry weight of the mucosa of the residual small intestine in resected pigs was restored (after 28 days) at a value similar to that measured for the intact small intestine in controls. Opposite to that, the dry weight of the mucosa of the residual intestine of resected + deafferented pigs was significantly lower, due to the absence of any compensatory hypertrophy. This difference did not result from any change in the food intake level. Therefore it was concluded that vagal afferences from the digestive tract are necessary in eliciting the compensatory hypertrophy. From these results

  14. Muscular and systemic correlates of resistance training-induced muscle hypertrophy.

    Directory of Open Access Journals (Sweden)

    Cameron J Mitchell

    Full Text Available PURPOSE: To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH, insulin like grow factor 1 (IGF-1 and interleukin 6 (IL-6], or intramuscular [skeletal muscle androgen receptor (AR protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. METHODS: Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk. Muscle biopsies were obtained before and after the training period and acutely 1 and 5 h after the first training session. Serum hormones and cytokines were measured immediately, 15, 30 and 60 minutes following the first and last training sessions of the study. RESULTS: Mean fiber area increased by 20% (range: -7 to 80%; P<0.001. Protein content of the AR was unchanged with training (fold change = 1.17 ± 0.61; P=0.19; however, there was a significant correlation between the changes in AR content and fiber area (r=0.60, P=0.023. Phosphorylation of p70S6K was elevated 5 hours following exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007. There was no relationship between the magnitude of the pre- or post-training exercise-induced changes in free testosterone, GH, or IGF-1 concentration and muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6 response was correlated with muscle hypertrophy (r=0.48, P=0.019. CONCLUSION: Post-exercise increases in circulating hormones are not related to hypertrophy following training. Exercise-induced changes in IL-6 correlated with hypertrophy, but the mechanism for the role of IL-6 in hypertrophy is not known. Acute increases, in p70S6K phosphorylation and changes in muscle AR protein content correlated with muscle hypertrophy implicating intramuscular rather than systemic processes in mediating hypertrophy.

  15. Calcineurin as a marker of myocardial hypertrophy in children with valvular congenital heart diseases

    Directory of Open Access Journals (Sweden)

    A. V. Kamenshchyk

    2015-06-01

    Full Text Available Aim. To identify interrelations between the calcineurin levels in children with valvular congenital heart diseases without heart failure and the echocardiography parameters of myocardial hypertrophy. Results: It was established the significantly decreased calcineurin level in congenial valvular heart diseases in children as well as an absence of correlations of the left ventricle myocardial mass and index with negative ones to the dimensions of right ventricle in comparison to healthy children of corresponding age. Conclusion: The obtained data testifies the importance of calcineurin system activity in the formation of pathologic myocardial hypertrophy in children with valvular congenital heart diseases and without manifestation of heart failure.

  16. Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis

    OpenAIRE

    Kun Yin; Liang Zhao; Dan Feng; Wenya Ma; Yu Liu; Yang Wang; Jing Liang; Fan Yang; Chongwei Bi; Hongyang Chen; Xingda Li; Yanjie Lu; Benzhi Cai

    2015-01-01

    Background/Aims: Low ambient temperature is an important risk factor for cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In this study, we aim to investigate if Resveratrol may inhibit cold exposure-induced cardiac hypertrophy in mice, and if so to clarify its molecular mechanism. Methods: Adult male mice were randomly assigned to Control group (kept at room temperature), Cold group (kept at low air temperature range from 3°C to 5°C) and Resveratrol treatment group...

  17. Macrophage Infiltration Is a Causative Factor for Ligamentum Flavum Hypertrophy through the Activation of Collagen Production in Fibroblasts.

    Science.gov (United States)

    Saito, Takeyuki; Hara, Masamitsu; Kumamaru, Hiromi; Kobayakawa, Kazu; Yokota, Kazuya; Kijima, Ken; Yoshizaki, Shingo; Harimaya, Katsumi; Matsumoto, Yoshihiro; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Inagaki, Yutaka; Shiba, Keiichiro; Nakashima, Yasuharu; Okada, Seiji

    2017-12-01

    Ligamentum flavum (LF) hypertrophy causes lumbar spinal canal stenosis, leading to leg pain and disability in activities of daily living in elderly individuals. Although previous studies have been performed on LF hypertrophy, its pathomechanisms have not been fully elucidated. In this study, we demonstrated that infiltrating macrophages were a causative factor for LF hypertrophy. Induction of macrophages into the mouse LF by applying a microinjury resulted in LF hypertrophy along with collagen accumulation and fibroblasts proliferation at the injured site, which were very similar to the characteristics observed in the severely hypertrophied LF of human. However, we found that macrophage depletion by injecting clodronate-containing liposomes counteracted LF hypertrophy even with microinjury. For identification of fibroblasts in the LF, we used collagen type I α2 linked to green fluorescent protein transgenic mice and selectively isolated green fluorescent protein-positive fibroblasts from the microinjured LF using laser microdissection. A quantitative RT-PCR on laser microdissection samples revealed that the gene expression of collagen markedly increased in the fibroblasts at the injured site with infiltrating macrophages compared with the uninjured location. These results suggested that macrophage infiltration was crucial for LF hypertrophy by stimulating collagen production in fibroblasts, providing better understanding of the pathophysiology of LF hypertrophy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Construction of the Database of Rat Repeated-dose Toxicity Tests of Pesticides for the Toxicological Characterization of Hepatocyte Hypertrophy.

    Science.gov (United States)

    Masuda, Akane; Masuda, Miyabi; Kawano, Takuya; Kitsunai, Yoko; Nakayama, Haruka; Nakajima, Hiroyuki; Kojima, Hiroyuki; Kitamura, Shigeyuki; Uramaru, Naoto; Hosaka, Takuomi; Sasaki, Takamitsu; Yoshinari, Kouichi

    2017-01-01

    Liver and hepatocyte hypertrophy can be induced by exposure to chemical compounds, but the mechanisms and toxicological characteristics of these phenomena have not yet been investigated extensively. In particular, it remains unclear whether the hepatocyte hypertrophy induced by chemical compounds should be judged as an adaptive response or an adverse effect. Thus, understanding of the toxicological characteristics of hepatocyte hypertrophy is of great importance to the safety evaluation of pesticides and other chemical compounds. To this end, we have constructed a database of potentially toxic pesticides. Using risk assessment reports of pesticides that are publicly available from the Food Safety Commission of Japan, we extracted all observations/findings that were based on 90-day subacute toxicity tests and 2-year chronic toxicity and carcinogenicity tests in rats. Analysis of the database revealed that hepatocyte hypertrophy was observed for 37-47% of the pesticides investigated (varying depending on sex and testing period), and that centrilobular hepatocyte hypertrophy was the most frequent among the various types of hepatocyte hypertrophy in both the 90-day and 2-year studies. The database constructed in this study enables us to investigate the relationships between hepatocyte hypertrophy and other toxicological observations/findings, and thus will be useful for characterizing hepatocyte hypertrophy.

  19. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S; van Geel, PP; Willenbrock, R; Pagel, [No Value; Pinto, YM; Buikema, H; van Gilst, WH; Lindschau, C; Paul, M; Inagami, T; Ganten, D; Urata, H

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT(1) receptors. However, the role of myocardial AT(1) receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  20. Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy

    DEFF Research Database (Denmark)

    Kroeldrup, L; Kjaergaard, S; Kirchhoff, Eva Maria

    2012-01-01

    Muscular hypertrophy is a very rare finding on foetal ultrasonography. We present a case with recurrent muscular hypertrophy, liver enlargement and polyhydramnios in two pregnancies. One pregnancy was terminated due to suspicion of a storage disease, whereas the other led to delivery of a boy...

  1. Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

    DEFF Research Database (Denmark)

    Søraas, Camilla L; Wachtell, Kristian; Okin, Peter M

    2010-01-01

    Regression of left ventricular (LV) hypertrophy and albuminuria in hypertension has previously been shown to reduce clinical cardiovascular events and death. We aimed to investigate the associations of regression of electrocardiographic (ECG) LV hypertrophy and albuminuria with the incidence of r...

  2. Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

    DEFF Research Database (Denmark)

    Søraas, Camilla L; Wachtell, Kristian; Okin, Peter M

    2010-01-01

    Regression of left ventricular (LV) hypertrophy and albuminuria in hypertension has previously been shown to reduce clinical cardiovascular events and death. We aimed to investigate the associations of regression of electrocardiographic (ECG) LV hypertrophy and albuminuria with the incidence of r...... of revascularization....

  3. Prevalence of human papillomavirus and Epstein-Barr virus DNA in Chinese children with tonsillar and/or adenoidal hypertrophy.

    Science.gov (United States)

    Xue, Xiao-cheng; Chen, Xiao-ping; Yao, Wen-hao; Zhang, Yi; Sun, Guang-bin; Tan, Xue-jun

    2014-06-01

    Tonsillar and adenoidal hypertrophy are prevalent otolaryngologic disorders in children, but their pathogenesis is largely unknown. The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNA in 146 tonsil and/or adenoid tissue specimens from 104 Chinese children with tonsillar and/or adenoidal hypertrophy were screened using flow-through hybridization gene-chip technology and real-time fluorescence-based quantitative PCR. Then, the relationships between the prevalence of the viruses and other clinical characteristics of tonsillar and/or adenoidal hypertrophy were analyzed. No patient had HPV DNA. EBV DNA was detected in 19/42 (45.2%) tonsil tissues and 72/104 (69.2%) adenoid tissue specimens (P hypertrophy. Adenoid tissues might more susceptible than tonsil tissues to EBV infection. In addition, EBV infection did not aggravate snoring in patients with tonsillar and/or adenoidal hypertrophy. © 2014 Wiley Periodicals, Inc.

  4. Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.

    Science.gov (United States)

    Le Quang, Khai; Bouchareb, Rihab; Lachance, Dominic; Laplante, Marc-André; El Husseini, Diala; Boulanger, Marie-Chloé; Fournier, Dominique; Fang, Xiang Ping; Avramoglu, Rita Kohen; Pibarot, Philippe; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2014-10-01

    This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. When compared with nondiabetic LDLr(-/-)/ApoB(100/100), diabetic LDLr(-/-)/ApoB(100/100)/IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr(-/-)/ApoB(100/100)/IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr(-/-)/ApoB(100/100) mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr(-/-)/ApoB(100/100)/IGF-II mice when compared with LDLr(-/-)/ApoB(100/100). Importantly, we found that peak aortic jet velocity was significantly increased in LDLr(-/-)/ApoB(100/100)/IGF-II mice versus LDLr(-/-)/ApoB(100/100) animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes (anp, bnp, b-mhc) in myocardial tissues and of osteogenic genes (spp1, bglap, runx2) in aortic tissues of diabetic mice. We have established the diabetes mellitus -prone LDLr(-/-)/ApoB(100/100)/IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis. © 2014 American Heart Association, Inc.

  5. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

    Science.gov (United States)

    Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

    2017-06-01

    Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure

    OpenAIRE

    Marques FZ; Prestes PR; Byars SG; Ritchie SC; Würtz P; Patel SK; Booth SA; Rana I; Minoda Y; Berzins SP; Curl CL; Bell JR; Wai B; Srivastava PM; Kangas AJ

    2017-01-01

    Background Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin‐2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression ne...

  7. Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy

    Science.gov (United States)

    Huang, Shuai; Zou, Xiao; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Liang, Ye-You; Deng, Chun-Yu; Kuang, Su-Juan; Zhang, Meng-Zhen; Liao, Yu-Lin; Zheng, Xi-Long; Yu, Xi-Yong; Shan, Zhi-Xin

    2015-01-01

    Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy. PMID:25583328

  8. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    Science.gov (United States)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  9. Exercise training does not improve cardiac function in compensated or decompensated left ventricular hypertrophy induced by aortic stenosis.

    Science.gov (United States)

    van Deel, Elza D; de Boer, Martine; Kuster, Diederik W; Boontje, Nicky M; Holemans, Patricia; Sipido, Karin R; van der Velden, Jolanda; Duncker, Dirk J

    2011-06-01

    There is ample evidence that regular exercise exerts beneficial effects on left ventricular (LV) hypertrophy, remodeling and dysfunction produced by ischemic heart disease or systemic hypertension. In contrast, the effects of exercise on pathological LV hypertrophy and dysfunction produced by LV outflow obstruction have not been studied to date. Consequently, we evaluated the effects of 8 weeks of voluntary wheel running in mice (which mitigates post-infarct LV dysfunction) on LV hypertrophy and dysfunction produced by mild (mTAC) and severe (sTAC) transverse aortic constriction. mTAC produced ~40% LV hypertrophy and increased myocardial expression of hypertrophy marker genes but did not affect LV function, SERCA2a protein levels, apoptosis or capillary density. Exercise had no effect on global LV hypertrophy and function in mTAC but increased interstitial collagen, and ANP expression. sTAC produced ~80% LV hypertrophy and further increased ANP expression and interstitial fibrosis and, in contrast with mTAC, also produced LV dilation, systolic as well as diastolic dysfunction, pulmonary congestion, apoptosis and capillary rarefaction and decreased SERCA2a and ryanodine receptor (RyR) protein levels. LV diastolic dysfunction was likely aggravated by elevated passive isometric force and Ca(2+)-sensitivity of myofilaments. Exercise training failed to mitigate the sTAC-induced LV hypertrophy and capillary rarefaction or the decreases in SERCA2a and RyR. Exercise attenuated the sTAC-induced increase in passive isometric force but did not affect myofilament Ca(2+)-sensitivity and tended to aggravate interstitial fibrosis. In conclusion, exercise had no effect on LV function in compensated and decompensated cardiac hypertrophy produced by LV outflow obstruction, suggesting that the effect of exercise on pathologic LV hypertrophy and dysfunction depends critically on the underlying cause. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Angiotensin II Facilitates Matrix Metalloproteinase-9-Mediated Myosin Light Chain Kinase Degradation in Pressure Overload-Induced Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Shun Wang

    2017-12-01

    Full Text Available Background/Aims: Angiotensin II (Ang II has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK, a specific kinase for the phosphorylation of myosin light chain 2 (MLC2, plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9 inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2, myosin phosphatase 2 (MYPT2, and calmodulin (CaM were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.

  11. Influence of dark phase restricted high fat feeding on myocardial adaptation in mice.

    Science.gov (United States)

    Tsai, Ju-Yun; Villegas-Montoya, Carolina; Boland, Brandon B; Blasier, Zachary; Egbejimi, Oluwaseun; Gonzalez, Raquel; Kueht, Michael; McElfresh, Tracy A; Brewer, Rachel A; Chandler, Margaret P; Bray, Molly S; Young, Martin E

    2013-02-01

    Prolonged high fat feeding is associated with myocardial contractile dysfunction in rodents. However, epidemiological data do not necessarily support the concept that fat-enriched diets adversely affect cardiac function in humans. When fed in an ad libitum manner, laboratory rodents consume chow throughout the day. In contrast, humans typically consume food only during the awake phase. Discrepancies between rodent and human feeding behaviors led us to hypothesize that the time of day at which dietary lipids are consumed significantly influences myocardial adaptation. In order to better mimic feeding behavior in humans, mice were fed (either a control or high fat diet) only during the 12-hour dark phase (i.e., no food was provided during the light phase). We report that compared to dark phase restricted control diet fed mice, mice fed a high fat diet during the dark phase exhibit: 1) essentially normal body weight gain and energy balance; 2) increased fatty acid oxidation at whole body, as well as skeletal and cardiac muscle (in the presence of insulin and/or at high workloads) levels; 3) induction of fatty acid responsive genes, including genes promoting triglyceride turnover in the heart; 4) no evidence of cardiac hypertrophy; and 5) persistence/improvement of myocardial contractile function, as assessed ex vivo. These data are consistent with the hypothesis that ingestion of dietary fat only during the more active/awake period allows adequate metabolic adaptation, thereby preserving myocardial contractile function. This article is part of a Special Issue entitled "Focus on cardiac metabolism". Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Augmented cardiac hypertrophy in response to pressure overload in mice lacking ELTD1.

    Directory of Open Access Journals (Sweden)

    Jinfeng Xiao

    Full Text Available BACKGROUND: Epidermal growth factor (EGF, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1 is developmentally upregulated in the heart. Little is known about the relationship between ELTD1 and cardiac diseases. Therefore, we aimed to clarify the role of ELTD1 in pressure overload-induced cardiac hypertrophy. METHODS AND RESULTS: C57BL/6J wild-type (WT mice and ELTD1-knockout (KO mice were subjected to left ventricular pressure overload by descending aortic banding (AB. KO mice exhibited more unfavorable cardiac remodeling than WT mice 28 days post AB; this remodeling was characterized by aggravated cardiomyocyte hypertrophy, thickening of the ventricular walls, dilated chambers, increased fibrosis, and blunted systolic and diastolic cardiac function. Analysis of signaling pathways revealed enhanced extracellular signal-regulated kinase (ERK and the c-Jun amino-terminal kinase (JNK phosphorylation in response to ELTD1 deletion. CONCLUSIONS: ELTD1 deficiency exacerbates cardiac hypertrophy and cardiac function induced by AB-induced pressure overload by promoting both cardiomyocyte hypertrophy and cardiac fibrosis. These effects are suggested to originate from the activation of the ERK and JNK pathways, suggesting that ELTD1 is a potential target for therapies that prevent the development of cardiac disease.

  13. The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling.

    Science.gov (United States)

    Ji, Yan-Xiao; Zhang, Peng; Zhang, Xiao-Jing; Zhao, Yi-Chao; Deng, Ke-Qiong; Jiang, Xi; Wang, Pi-Xiao; Huang, Zan; Li, Hongliang

    2016-06-01

    Tumour necrosis factor receptor-associated factor 6 (TRAF6) is a ubiquitin E3 ligase that regulates important biological processes. However, the role of TRAF6 in cardiac hypertrophy remains unknown. Here, we show that TRAF6 levels are increased in human and murine hypertrophied hearts, which is regulated by reactive oxygen species (ROS) production. Cardiac-specific Traf6 overexpression exacerbates cardiac hypertrophy in response to pressure overload or angiotensin II (Ang II) challenge, whereas Traf6 deficiency causes an alleviated hypertrophic phenotype in mice. Mechanistically, we show that ROS, generated during hypertrophic progression, triggers TRAF6 auto-ubiquitination that facilitates recruitment of TAB2 and its binding to transforming growth factor beta-activated kinase 1 (TAK1), which, in turn, enables the direct TRAF6-TAK1 interaction and promotes TAK1 ubiquitination. The binding of TRAF6 to TAK1 and the induction of TAK1 ubiquitination and activation are indispensable for TRAF6-regulated cardiac remodelling. Taken together, we define TRAF6 as an essential molecular switch leading to cardiac hypertrophy in a TAK1-dependent manner.

  14. Clenbuterol induces cardiac myocyte hypertrophy via paracrine signalling and fibroblast-derived IGF-1.

    Science.gov (United States)

    Bhavsar, Pankaj K; Brand, Nigel J; Felkin, Leanne E; Luther, Pradeep K; Cullen, Martin E; Yacoub, Magdi H; Barton, Paul J R

    2010-12-01

    The β(2)-selective adrenoreceptor agonist clenbuterol promotes both skeletal and cardiac muscle hypertrophy and is undergoing clinical trials in the treatment of muscle wasting and heart failure. We have previously demonstrated that clenbuterol induces a mild physiological ventricular hypertrophy in vivo with normal contractile function and without induction of α-skeletal muscle actin (αSkA), a marker of pathological hypertrophy. The mechanisms of this response remain poorly defined. In this study, we examine the direct action of clenbuterol on cardiocyte cultures in vitro. Clenbuterol treatment resulted in increased cell size of cardiac myocytes with increased protein accumulation and myofibrillar organisation characteristic of hypertrophic growth. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed elevated mRNA expression of ANP and brain natriuretic peptide (BNP) but without change in αSkA, consistent with physiological hypertrophic growth. Clenbuterol-treated cultures also showed elevated insulin-like growth factor I (IGF-1) mRNA and activation of the protein kinase Akt. Addition of either IGF-1 receptor-blocking antibodies or LY294002 in order to inhibit phosphatidylinositol 3-kinase, a downstream effector of the IGF-1 receptor, inhibited the hypertrophic response indicating that IGF-1 signalling is required. IGF-1 expression localised primarily to the minor population of cardiac fibroblasts present in the cardiocyte cultures. Together these data show that clenbuterol acts to induce mild cardiac hypertrophy in cardiac myocytes via paracrine signalling involving fibroblast-derived IGF-1.

  15. [A swollen, painless calf caused by neurogenic muscle (pseudo)-hypertrophy

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Zwarts, M.J.; Engelen, B.G.M. van

    2003-01-01

    Neurogenic muscle (pseudo) hypertrophy of the calf was diagnosed in a 60-year-old man, who presented with chronic, painless and unilateral calf enlargement caused by a chronic S1 radiculopathy due to a lumbar disc hernia in the L5-S1 interspace. The differential diagnosis of a swelling of the calf

  16. Dynamics of the salivary gland hypertrophy virus in laboratory colonies of Glossina pallidipes (Diptera: Glossinidae)

    NARCIS (Netherlands)

    Abd-Alla, A.M.M.; Kariithi, H.M.; Parker, A.G.; Robinson, A.S.; Kiflom, M.; Bergoin, M.; Vreysen, M.J.B.

    2010-01-01

    Many species of tsetse flies are infected by a virus that causes salivary gland hypertrophy (SGH) and the virus isolated from Glossina pallidipes (GpSGHV) has recently been sequenced. Flies with SGH have a reduced fecundity and fertility. To better understand the impact of this virus in a laboratory

  17. Eccentric Left Ventricular Hypertrophy and Sudden Death in Patients with End-Stage Kidney Disease

    NARCIS (Netherlands)

    De Roij Van Zuijdewijn, Camiel L M; Hansildaar, Romy; Bots, Michiel L.; Blankestijn, Peter J.; Van Den Dorpel, Marinus A.; Grooteman, Muriel P C; Kamp, Otto; Ter Wee, Piet M.; Nubé, Menso J.

    2015-01-01

    Background/Aims: Both all-cause and cardiovascular mortality risks are extremely high in patients with end-stage kidney disease (ESKD). Sudden death accounts for approximately one-quarter of all fatal events. Left ventricular hypertrophy (LVH) is a known risk factor for mortality and can be divided

  18. [Sexual problems in patients with prostate cancer and those with benign prostatic hypertrophy].

    Science.gov (United States)

    Danilin, J E; Marilov, V V; Brukhin, A E

    2011-03-23

    We use the word "tumour" both for a benign prostatic hypertrophy and for a prostatic cancer. The psycho-emotional reactions from a man suffering from these illnesses could be different depending on the kind of tumour, but could be similar especially concerning sexual problems connected with the specific affliction. Hence the necessity also to consider beneficial a psychotherapeutic and sexotherapeutic intervention.

  19. TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

    NARCIS (Netherlands)

    MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

    1993-01-01

    The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

  20. TRANSURETHRAL RADIOFREQUENCY HEATING OR THERMOTHERAPY FOR BENIGN PROSTATIC HYPERTROPHY - A PROSPECTIVE TRIAL ON 65 CONSECUTIVE CASES

    NARCIS (Netherlands)

    MEIER, AHP; WEIL, EHJ; VANDOORN, ESCV; VERHAEGH, GTCM; JANKNEGT, RA

    1992-01-01

    65 consecutive cases with symptomatic benign prostate hypertrophy were treated with transurethral radiowave thermotherapy (TURF) using the Thermex-II at a temperature of 44.5-degrees-C. We report uroflowmetry and symptom scores after a follow-up of 6 months. The mean age was 63 years, the mean

  1. Salivary gland hypertrophy viruses (SGHVs): a novel group of insect pathogenic viruses

    Science.gov (United States)

    Salivary gland hypertrophy viruses (SGHVs) are a unique, unclassified group of entomopathogenic, double-stranded DNA viruses that have been reported from three genera of Diptera. These viruses replicate in nuclei of salivary gland cells in adult flies, inducing gland enlargement with little obvious ...

  2. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Nielsen, Mette Lundgren; Pareek, Manan; Gerke, O

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population...

  3. Classification of Hypertrophy of Labia Minora: Consideration of a Multiple Component Approach.

    Science.gov (United States)

    González, Pablo I

    2015-11-01

    Labia minora hypertrophy of unknown and under-reported incidence in the general population is considered a variant of normal anatomy. Its origin is multi-factorial including genetic, hormonal, and infectious factors, and voluntary elongation of the labiae minorae in some cultures. Consults with patients bothered by this condition have been increasing with patients complaining of poor aesthetics and symptoms such as difficulty with vaginal secretions, vulvovaginitis, chronic irritation, and superficial dyspareunia, all of which can have a negative effect on these patients' sexuality and self esteem. Surgical management of labial hypertrophy is an option for women with these physical complaints or aesthetic issues. Labia minora hypertrophy can consist of multiple components, including the clitoral hood, lateral prepuce, frenulum, and the body of the labia minora. To date, there is not a consensus in the literature with respect to the classification and definition of varying grades of hypertrophy, aside from measurement of the length in centimeters. In order to offer patients the most appropriate surgical technique, an objective and understandable classification that can be used as part of the preoperative evaluation is necessary. Such a classification should have the aim of offering patients the best cosmetic and functional results with the fewest complications.

  4. Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy : Magnetic resonance imaging versus echocardiography

    NARCIS (Netherlands)

    Posma, JL; Blanksma, PK; vanderWall, EE; Hamer, HPM; Mooyaart, EL; Lie, KI

    1996-01-01

    To compare the diagnostic value of spin-echo magnetic resonance (MR) imaging and transthoracic echocardiography in quantitative assessment of the extent of hypertrophy in patients with hypertrophic cardiomyopathy (HCM), we examined 52 consecutive patients with HCM. The Spirito-Maron and Wigle

  5. Localised hypertrophy of semimembranous muscle. A report of two cases in athletes.

    Science.gov (United States)

    Carrozza, M; Giombini, A; Dragoni, S; De Carolis, M; Bizzarri, F

    2001-09-01

    We report two cases of localised hypertrophy of semimembranous muscle in young athletes diagnosed with ultrasonography, flow color-Doppler and MRI. The symptomatic case had the resolution of the pain after one month rest. At one year follow-up both cases are still asymptomatic, without any further increase of the hypertrophyc masses.

  6. Low-load bench press and push-up induce similar muscle hypertrophy and strength gain

    National Research Council Canada - National Science Library

    Naoki Kikuchi; Koichi Nakazato

    2017-01-01

    ...) bench press on muscle hypertrophy and strength gain in men. Methods: Eighteen male participants (age, 20.2 ± 0.73 years, range: 19−22 years, height: 169.8 ± 4.4 cm, weight: 64.5 ± 4.7 kg...

  7. Effects of chronic treprostinil treatment on experimental right heart hypertrophy and failure.

    Science.gov (United States)

    Axelgaard, Sofie; Holmboe, Sarah; Ringgaard, Steffen; Hillgaard, Thomas K; Andersen, Stine; Hansen, Mona S; Andersen, Asger; Nielsen-Kudsk, Jens E

    2017-01-01

    Right heart function is an important predictor of morbidity and mortality in pulmonary arterial hypertension and many CHD. We investigated whether treatment with the prostacyclin analogue treprostinil could prevent pressure overload-induced right ventricular hypertrophy and failure. Male Wistar rats were randomised to severe pulmonary trunk banding with a 0.5-mm banding clip (n=41), moderate pulmonary trunk banding with a 0.6-mm banding clip (n=36), or sham procedure (n=10). The banded rats were randomised to 6 weeks of treatment with a moderate dose of treprostinil (300 ng/kg/minute), a high dose of treprostinil (900 ng/kg/minute), or vehicle. Pulmonary trunk banding effectively induced hypertrophy, dilatation, and decreased right ventricular function. The severely banded animals presented with decompensated heart failure with extracardial manifestations. Treatment with treprostinil neither reduced right ventricular hypertrophy nor improved right ventricular function. In the pulmonary trunk banding model of pressure overload-induced right ventricular hypertrophy and failure, moderate- and high-dose treatment with treprostinil did not improve right ventricular function neither in compensated nor in decompensated right heart failure.

  8. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  9. [Obstructive sleep apnea-hypopnea syndrome in children: beyond adenotonsillar hypertrophy].

    Science.gov (United States)

    Esteller, Eduard

    2015-01-01

    The prevalence of obstructive sleep apnea-hypopnea syndrome in the general childhood population is 1-2% and the most common cause is adenotonsillar hypertrophy. However, beyond adenotonsillar hypertrophy, there are other highly prevalent causes of this syndrome in children. The causes are often multifactorial and include muscular hypotonia, dentofacial abnormalities, soft tissue hypertrophy of the airway, and neurological disorders). Collaboration between different specialties involved in the care of these children is essential, given the wide variability of conditions and how frequently different factors are involved in their genesis, as well as the different treatments to be applied. We carried out a wide literature review of other causes of obstructive sleep apnea-hypopnea syndrome in children, beyond adenotonsillar hypertrophy. We organised the prevalence of this syndrome in each pathology and the reasons that cause it, as well as their interactions and management, in a consistent manner. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  10. Uni- or bi-ventricular hypertrophy and susceptibility to drug-induced torsades de pointes.

    Science.gov (United States)

    Panyasing, Yaowalak; Kijtawornrat, Anusak; Del Rio, Carlos; Carnes, Cynthia; Hamlin, Robert L

    2010-01-01

    Cardiac hypertrophy is an independent risk factor for torsades de pointes (TdP), a polymorphic ventricular tachycardia that is often drug-induced, that may evolve into ventricular fibrillation and sudden death. Therefore this study was designed to determine if right (RVH), left (LVH), or biventricular (BVH) hypertrophy increases susceptibility to drug-induced TdP. Rabbits were separated into 4 groups: control or RVH, LVH, BVH (studied 8weeks after banding of one or both great arteries). ECGs were recorded continuously under anesthesia after baseline and after rabbits received escalating doses of torsadogens (dofetilide, clofilium and terfenadine) or non-torsadogens (cilobradine, diltiazem and vehicle). The following parameters were measured [RR, PQ, QRS and QT] or calculated [QTc (F), short term variability of QT interval]. Generally, torsadogenicity for the compounds tested was dofetilide>clofilium>terfenadine, and there was no TdP following cilobradine, diltiazem or vehicle. In general the susceptibility to TdP was RVH>BVH>LVH>control. Rabbits with RVH developed TdP much more prevalently than for those with either LVH or BVH (p<0.05). At the low dose of dofetilide, LVH was actually protective. Rabbits with any form of hypertrophy develop prolongation of QT, QTc and increased QT instability. Rabbits with any form of hypertrophy are more prone to arrhythmia than normals in response to known torsadogens. 2010 Elsevier Inc. All rights reserved.

  11. Possibility of leg muscle hypertrophy by ambulation in older adults: a brief review.

    Science.gov (United States)

    Ozaki, Hayao; Loenneke, Jeremy P; Thiebaud, Robert S; Stager, Joel M; Abe, Takashi

    2013-01-01

    It is known that ambulatory exercises such as brisk walking and jogging are potent stimuli for improving aerobic capacity, but it is less understood whether ambulatory exercise can increase leg muscle size and function. The purpose of this brief review is to discuss whether or not ambulatory exercise elicits leg muscle hypertrophy in older adults. Daily ambulatory activity with moderate (>3 metabolic equivalents [METs], which is defined as the ratio of the work metabolic rate to the resting metabolic rate) intensity estimated by accelerometer is positively correlated with lower body muscle size and function in older adults. Although there is conflicting data on the effects of short-term training, it is possible that relatively long periods of walking, jogging, or intermittent running for over half a year can increase leg muscle size among older adults. In addition, slow-walk training with a combination of leg muscle blood flow restriction elicits muscle hypertrophy only in the blood flow restricted leg muscles. Competitive marathon running and regular high intensity distance running in young and middle-aged adults may not produce leg muscle hypertrophy due to insufficient recovery from the damaging running bout, although there have been no studies that have investigated the effects of running on leg muscle morphology in older subjects. It is clear that skeletal muscle hypertrophy can occur independently of exercise mode and load.

  12. Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation

    DEFF Research Database (Denmark)

    Ravn, Nathja; Zois, Nora Elisabeth; Moesgaard, Sophia Gry

    2014-01-01

    traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. RESULTS: Eight...

  13. Long Non-Coding RNA-ROR Mediates the Reprogramming in Cardiac Hypertrophy.

    Science.gov (United States)

    Jiang, Feng; Zhou, Xiangyu; Huang, Jing

    2016-01-01

    Cardiac hypertrophy associated with various cardiovascular diseases results in heart failure and sudden death. A clear understanding of the mechanisms of hypertrophy will benefit the development of novel therapies. Long non-coding RNAs (lncRNAs) have been shown to play essential roles in many biological process, however, whether lncRNA-ROR plays functional roles in the reprogramming of cardiomyocyte remains unclear. Here we show that lncRNA-ROR plays important roles in the pathogenesis of cardiac hypertrophy. In hypertrophic heart and cardiomyocytes, the expression of lncRNA-ROR is dramatically increased, downregulation of which attenuates the hypertrophic responses. Furthermore, the expression of lncRNA-ROR negatively correlates with miR-133, whose expression is increased when lncRNA-ROR is knocked down. In line with this, overexpression of miR-133 prevents the elevation of lncRNA-ROR and re-expression of ANP and BNP in cardiomyocytes subject to phenylephrine treatment. Taken together, our study demonstrates that lncRNA-ROR promotes cardiac hypertrophy via interacting with miR-133, indicating that lncRNA-ROR could be targeted for developing novel antihypertrophic therapeutics.

  14. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

    Science.gov (United States)

    Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

    2015-09-01

    The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

  15. Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ming Xu

    2007-02-01

    Full Text Available Pressure overload-induced hypertrophy is a key step leading to heart failure. The Ca(2+-induced Ca(2+ release (CICR process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca(2+ channel (LCC and ryanodine receptors (RyRs in aortic stenosis rat models of compensated (CHT and decompensated (DHT hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of "intermolecular failure." Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca(2+ release, visualized as "Ca(2+ spikes," became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca(2+ transients in CHT. These data suggested that, within a certain limit, termed the "stability margin," mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of "hidden" intermolecular failure in CHT has important clinical implications.

  16. Long-Term Prognosis after Myectomy in Hypertrophic Obstructive Cardiomyopathy with Severe Left Ventricular Hypertrophy.

    Science.gov (United States)

    An, Shuoyan; Fan, Chaomei; Yang, Yinjian; Hang, Fei; Wang, Zhimin; Zhang, Yuhui; Zhang, Jian

    2018-01-05

    Patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular hypertrophy (maximal left ventricular wall thickness ≥30 mm) are at high risk of sudden cardiac death (SCD). In this study, we aimed to determine whether HOCM patients with severe hypertrophy had a lower incidence of SCD after myectomy. HOCM patients with severe hypertrophy were consecutively enrolled from Fuwai Hospital in China between 2000 and 2013. Long-term outcomes were retrospectively compared between the 2 groups, namely the myectomy group and medical group. A total of 244 patients (118 in the myectomy group and 126 in the medical group) were involved. The mean follow-up durations for the myectomy and medical groups were 5.07 ± 3.73 and 6.23 ± 4.15 years, respectively. During the follow-up period, the annual cardiovascular mortality rate was 0.84% in the myectomy group and 2.04% in the medical group (p = 0.041). The annual SCD rate was 0.33% in the myectomy group and 1.40% in the medical group (p = 0.040). Multivariate Cox regression analysis showed that myectomy was independently associated with lower rates of cardiovascular death and SCD. In HOCM patients with severe hypertrophy, those that underwent myectomy had a lower risk of cardiovascular death and SCD than those treated with medicines only. © 2018 S. Karger AG, Basel.

  17. Exobasidium ferrugineae sp. nov., associated with hypertrophied flowers of Lyonia ferruginea in the southeastern USA

    Science.gov (United States)

    Aaron H. Kennedy; Nisse A. Goldberg; Anderw M. Minnis

    2012-01-01

    Exobasidium ferrugineae, associated with hypertrophied flowers and less commonly leaves of Lyonia ferruginea (rusty staggerbush), is formally described here as a new species. Morphological and DNA sequence (ITS, nLSU) data are provided. Phylogenetic analyses confirm that it is not conspecific with any species of ...

  18. Electrophysiological characteristics of pressure overload-induced cardiac hypertrophy and its influence on ventricular arrhythmias.

    Science.gov (United States)

    Chen, Xiaowei; Qin, Mu; Jiang, Weifeng; Zhang, Yu; Liu, Xu

    2017-01-01

    To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias. Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation. Using the Langendorff method of isolated heart perfusion, monophasic action potentials (MAPs) and the effective refractory period (ERP) at different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) were measured, and the induction rate of ventricular tachyarrhythmias was observed under programmed electrical stimulus (PES) and burst stimulus. Whole-cell patch-clamp was used to obtain the I-V characteristics of voltage-gated potassium channels in cardiomyocytes of different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) as well as the channels' properties of steady-state inactivation and recovery from inactivation. The ratio of heart weight to body weight and the ratio of left ventricular weight to body weight in the surgery group were significantly higher than those in the control group (P cardiac hypertrophy, and the spatially heterogeneous changes of the channels may increase the occurrence of ventricular arrhythmias that accompany cardiac hypertrophy.

  19. Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy in vivo

    NARCIS (Netherlands)

    Kuipers, Irma; Li, Jiang; Vreeswijk-Baudoin, Inge; Koster, Johan; van der Harst, Pim; Sillje, Herman H. W.; Kuipers, Folkert; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; de Boer, Rudolf A.

    2010-01-01

    Liver X receptor (LXR) is a nuclear receptor regulating cholesterol metabolism. Liver X receptor has also been shown to exert anti-proliferative and anti-inflammatory properties. In this study, we evaluated the effect of LXR activation on cardiac hypertrophy in vitro and in vivo. Treatment with the

  20. Long Non-Coding RNA-ROR Mediates the Reprogramming in Cardiac Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    Full Text Available Cardiac hypertrophy associated with various cardiovascular diseases results in heart failure and sudden death. A clear understanding of the mechanisms of hypertrophy will benefit the development of novel therapies. Long non-coding RNAs (lncRNAs have been shown to play essential roles in many biological process, however, whether lncRNA-ROR plays functional roles in the reprogramming of cardiomyocyte remains unclear.Here we show that lncRNA-ROR plays important roles in the pathogenesis of cardiac hypertrophy. In hypertrophic heart and cardiomyocytes, the expression of lncRNA-ROR is dramatically increased, downregulation of which attenuates the hypertrophic responses. Furthermore, the expression of lncRNA-ROR negatively correlates with miR-133, whose expression is increased when lncRNA-ROR is knocked down. In line with this, overexpression of miR-133 prevents the elevation of lncRNA-ROR and re-expression of ANP and BNP in cardiomyocytes subject to phenylephrine treatment.Taken together, our study demonstrates that lncRNA-ROR promotes cardiac hypertrophy via interacting with miR-133, indicating that lncRNA-ROR could be targeted for developing novel antihypertrophic therapeutics.

  1. Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats

    NARCIS (Netherlands)

    Tian, Xiao-Li; Pinto, Yigal Martin; Costerousse, Olivier; Franz, Wolfgang M.; Lippoldt, Andrea; Hoffmann, Sigrid; Unger, Thomas; Paul, Martin

    2004-01-01

    Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains

  2. Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice.

    Science.gov (United States)

    Pei, Jian-Fei; Yan, Yun-Fei; Tang, Xiaoqiang; Zhang, Yang; Cui, Shen-Shen; Zhang, Zhu-Qin; Chen, Hou-Zao; Liu, De-Pei

    2016-11-01

    Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene (PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type (WT) control. The same protective tendency was also observed with an Apoe -/- background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.

  3. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy

    Science.gov (United States)

    Deng, Ke-Qiong; Wang, Aibing; Ji, Yan-Xiao; Zhang, Xiao-Jing; Fang, Jing; Zhang, Yan; Zhang, Peng; Jiang, Xi; Gao, Lu; Zhu, Xue-Yong; Zhao, Yichao; Gao, Lingchen; Yang, Qinglin; Zhu, Xue-Hai; Wei, Xiang; Pu, Jun; Li, Hongliang

    2016-01-01

    Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID:27249321

  4. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C

    1993-01-01

    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients ...

  5. Airway evaluation by indirect laryngoscopy in patients with lingual tonsillar hypertrophy.

    Science.gov (United States)

    Sánchez-Morillo, Jorge; Gómez-Diago, Lorena; Rodríguez-Gimillo, Pablo; Herrera-Collado, Raúl; Puchol-Castillo, Jorge; Mompó-Romero, Luis

    2013-01-01

    Prevalence of the lingual tonsillar hypertrophy is unknown but it is believed that its presence is associated with the difficult airway. To investigate this, indirect laryngoscopy was performed on patients in the preoperative evaluation and this pathology was diagnosed. The relationship with difficulty of viewing the larynx, intubation and ventilation, under general anaesthesia and using direct laryngoscopy, was then studied. We performed the demographic variable checks and tests for predicting difficult intubation (mouth opening, thyromental distance, cervical flexion-extension, neck thickness and Mallampati test), in the preoperative step on 300 patients who were going to be submitted to general anaesthesia. We then performed indirect laryngoscopy on them using a 70° rigid laryngoscope to ascertain the frequency of appearance of lingual tonsillar hypertrophy. Next, under general anaesthesia, we carried out direct laryngoscopy to verify whether there was difficulty in viewing the larynx and intubation and ventilation. We then investigated the association of demographic predictors of difficult intubation, including indirect laryngoscopy, with the presence of this condition. Prevalence of lingual tonsillar hypertrophy was 2%. No relationship between the appearance of this entity and the difficulty of viewing the larynx, intubation and ventilation was found. Only indirect laryngoscopy was linked to the appearance of this pathology. Lingual tonsillar hypertrophy is a relatively frequent disorder, whose presence is not usually associated with difficult airway. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  6. Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model

    Directory of Open Access Journals (Sweden)

    Andrew D. Vigotsky

    2015-11-01

    Full Text Available Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.

  7. Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model.

    Science.gov (United States)

    Vigotsky, Andrew D; Contreras, Bret; Beardsley, Chris

    2015-01-01

    Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA) lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA) of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.

  8. Nuclear Factor of Activated T cells (NFAT): key regulator of cardiac hypertrophy and skeletal muscle adaptation

    NARCIS (Netherlands)

    Bourajjaj, M.

    2008-01-01

    Despite significant progress in the prevention and treatment of cardiovascular diseases, heart failure is still a leading cause of morbidity and mortality in industrial countries. Sustained cardiac hypertrophy, which is defined as an increase in heart size resulting from an increase in cardiomyocyte

  9. Inhibition of Cardiomyocytes Hypertrophy by Resveratrol Is Associated with Amelioration of Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Yan Lin

    2016-07-01

    Full Text Available Background/Aims: Resveratrol (Res, a polyphenol antioxidant found in red wine, has been shown to play a cardioprotective role. This study was undertaken to investigate whether Res can protect the heart suffering from hypertrophy injuries induced by isoproterenol (ISO, and whether the protective effect is mediated by endoplasmic reticulum (ER stress. Methods: Cardiomyocytes were randomly assigned to the control group, ISO group (100 nM ISO for 48 h, Res + ISO group (50 μM Res and 100 nM ISO for 48 h and Res group (50 μM Res for 48h only. Hypertrophy was estimated by measuring the cell surface area and the atrial natriuretic peptide (ANP gene expression. Apoptosis was measured using Hoechst 33258 staining and transmission electron microscopy. Protein expression of ER stress and apoptosis factors was analyzed using Western Blot analysis. Results: Res effectively suppress the cardiomyocytes hypertrophy and apoptosis induced by ISO, characterized by the reduction of the myocardial cell surface area, the ANP gene expression, the LDH and MDA leakage amount and the rate of cell apoptosis, while decrease of the protein expression of GRP78, GRP94 and CHOP, and reverse the expression of Bcl-2 and Bax. Conclusion: In summary, Res treatment effectively suppressed myocardial hypertrophy and apoptosis at least partially via inhibiting ER stress.

  10. Hypertrophy in port-wine stains: Prevalence and patient characteristics in a large patient cohort

    NARCIS (Netherlands)

    van Drooge, Anne Margreet; Beek, Johan F.; van der Veen, J. P. Wietze; van der Horst, Chantal M. A. M.; Wolkerstorfer, Albert

    2012-01-01

    Background: Port-wine stains (PWS) may thicken and darken with age. Little is known about the pathogenesis and epidemiology of PWS hypertrophy because of the lack of large studies. Objective: We sought to assess the prevalence and characteristics of patients with hypertrophic PWS. Methods: Medical

  11. Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study

    Directory of Open Access Journals (Sweden)

    Yongbo Wang

    2016-01-01

    Full Text Available Selenium (Se is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%–27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile.

  12. Oral insulin improves metabolic parameters in high fat diet fed rats

    Directory of Open Access Journals (Sweden)

    LEANDRO C. LIPINSKI

    2017-08-01

    Full Text Available ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL standard chow group; high fat diet low carbohydrates group (HFD and HFD plus daily oral 20U insulin gavage (HFD+INS. Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001, fasting glucose and triglycerides serum levels (p<0,05 an increased intestinal weight of distal ileum (P<0,05. Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05 in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

  13. GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Javier Duran

    Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

  14. Vascular Endothelial Growth Factor Prevents Endothelial-to-Mesenchymal Transition in Hypertrophy.

    Science.gov (United States)

    Illigens, Ben M-W; Casar Berazaluce, Alejandra; Poutias, Dimitrios; Gasser, Robert; Del Nido, Pedro J; Friehs, Ingeborg

    2017-09-01

    In hypertrophy, progressive loss of function caused by impaired diastolic compliance correlates with advancing cardiac fibrosis. Endothelial cells contribute to this process through endothelial-to-mesenchymal transition (EndMT) resulting from inductive signals such as transforming growth factor (TGF-β). Vascular endothelial growth factor (VEGF) has proven effective in preserving systolic function and delaying the onset of failure. In this study, we hypothesize that VEGF inhibits EndMT and prevents cardiac fibrosis, thereby preserving diastolic function. The descending aorta was banded in newborn rabbits. At 4 and 6 weeks, hypertrophied animals were treated with intrapericardial VEGF protein and compared with controls (n = 7 per group). Weekly transthoracic echocardiography measured peak systolic stress. At 7 weeks, diastolic stiffness was determined through pressure-volume curves, fibrosis by Masson trichrome stain and hydroxyproline assay, EndMT by immunohistochemistry, and activation of TGF-β and SMAD2/3 by quantitative real-time polymerase chain reaction. Peak systolic stress was preserved during the entire observation period, and diastolic compliance was maintained in treated animals (hypertrophied: 20 ± 1 vs treated: 11 ± 3 and controls: 12 ± 2; p Masson trichrome (hypertrophied: 3.1 ± 0.9 vs treated: 1.8 ± 0.6) and by hydroxyproline assay (hypertrophied: 2.8 ± 0.6 vs treated: 1.4 ± 0.4; p < 0.05). Fluorescent immunostaining showed active EndMT in the hypertrophied group but significantly less in treated hearts, which was directly associated with a significant increase in TGF-β/SMAD-2 messenger RNA expression. EndMT contributes to cardiac fibrosis in hypertrophied hearts. VEGF treatment inhibits EndMT and prevents the deposition of collagen that leads to myocardial stiffness through TGF-β/SMAD-dependent activation. This presents a therapeutic opportunity to prevent diastolic failure and preserve cardiac function in pressure-loaded hearts

  15. Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.

    Science.gov (United States)

    Luckey, Stephen W; Haines, Chris D; Konhilas, John P; Luczak, Elizabeth D; Messmer-Kratzsch, Antke; Leinwand, Leslie A

    2017-12-01

    A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1 -/- ), and mice deficient in cyclin D2 (cyclin D2 -/- ). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2 -/- mice. Cardiac function was not impacted in the cyclin D2 -/- mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2 -/- mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise

  16. Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?

    Science.gov (United States)

    Seneff, Stephanie; Wainwright, Glyn; Mascitelli, Luca

    2011-02-01

    The metabolic syndrome (MetS) is manifested by a lipid triad which includes elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol, by central obesity (central adiposity), insulin resistance, glucose intolerance and elevated blood pressure, and it is associated with an increased risk of type 2 diabetes and coronary heart disease. We have developed a new hypothesis regarding MetS as a consequence of a high intake in carbohydrates and food with a high glycemic index, particularly fructose, and relatively low intake of cholesterol and saturated fat. We support our arguments through animal studies which have shown that exposure of the liver to increased quantities of fructose leads to rapid stimulation of lipogenesis and accumulation of triglycerides. The adipocytes store triglycerides in lipid droplets, leading to adipocyte hypertrophy. Adipocyte hypertrophy is associated with macrophage accumulation in adipose tissue. An important modulator of obesity-associated macrophage responses in white adipose tissue is the death of adipocytes. Excess exposure to fructose intake determines the liver to metabolize high doses of fructose, producing increased levels of fructose end products, like glyceraldehyde and dihydroxyacetone phosphate, that can converge with the glycolytic pathway. Fructose also leads to increased levels of advanced glycation end products. The macrophages exposed to advanced glycation end products become dysfunctional and, on entry into the artery wall, contribute to plaque formation and thrombosis.

  17. Splice variants of enigma homolog, differentially expressed during heart development, promote or prevent hypertrophy.

    Science.gov (United States)

    Yamazaki, Tomoko; Wälchli, Sébastien; Fujita, Toshitsugu; Ryser, Stephan; Hoshijima, Masahiko; Schlegel, Werner; Kuroda, Shun'ichi; Maturana, Andrés D

    2010-06-01

    Proteins with a PDZ (for PSD-95, DLG, ZO-1) and one to three LIM (for Lin11, Isl-1, Mec-3) domains are scaffolding sarcomeric and cytoskeletal elements that form structured muscle fibres and provide for the link to intracellular signalling by selectively associating protein kinases, ion channels, and transcription factors with the mechanical stress-strain sensors. Enigma homolog (ENH) is a PDZ-LIM protein with four splice variants: ENH1 with an N-terminal PDZ domain and three C-terminal LIM domains and ENH2, ENH3, and ENH4 without LIM domains. We addressed the functional role of ENH alternative splicing. We studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal, and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3, and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy, producing an ENH isoform pattern similar to that of neonatal heart. Next, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When overexpressed in rat neonatal cardiomyocytes, ENH1 promoted the expression of hypertrophy markers and increased cell volume, whereas, on the contrary, ENH4 overexpression prevented these changes. Antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signalling occurring during embryonic development and/or heart hypertrophy.

  18. Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

    Directory of Open Access Journals (Sweden)

    Liming Pan

    Full Text Available This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418 on cardiac hypertrophy caused by aortic banding (AB, phenylephrine (PE or angiotensin II (Ang II in vivo and in vitro.The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM or hypertrophic cardiomyopathy (HCM and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting.ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro.ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

  19. Myocardial hypertrophy and intracardial hemodynamics in children with bicuspid aortic valve

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    А. V. Kamenshchyk

    2017-08-01

    Full Text Available Bicuspid aortic valve is one of the most common congenital heart diseases with low manifestation in childhood and severe consequences in adults that determines the importance in early diagnostics of myocardial changes in this anomaly. According to the literature the polymorphisms in the genes of NFATC family could result both in impaired embriogenetic valves formation and development of postnatal myocardial hypertrophy. The aim of the study was to detect the early changes of intracardial hemodynamics at aortic valve in children with bicuspid aortic valve (BAV and establish their interrelations to the signs of myocardial hypertrophy in these children. Materials and methods: Dopplerograhphic study of basic intracardiac hemodynamics parameters in 38 children with BAV and in 28 children of control group was conducted. The results were processed statistically by Student’s t-test, correlation analysis and multiple regression. Results: In the result of study the moderate concentric left ventricle myocardial hypertrophy development was detected in 62 % of children with BAV which is accompanying to significant increasing of blood flow velocity and pressure gradient at aortic valve. There were not established significant correlations between the parameters of hemodynamics at valve and left ventricle’s posterior wall depth and septum depth whereas the highest inputs of these values were obtained in the left ventricle systolic dimension and volume and less in the hypertrophic signs. Conclusions: In children with BAV the moderate concentric myocardial hypertrophy with significant changes of intracardial hemodynamics at aortic valve takes place with the highest inputs in left ventricle volumetric values The obtained data serves as a substantiation for the treatment and prevention of it further development. bicuspid aortic valve; children; heart hypertrophy; dopplerechocardiography; hemodynamics; regression analysis

  20. NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.

    Science.gov (United States)

    Liao, Xing-Hua; Wang, Nan; Zhao, Dong-Wei; Zheng, De-Liang; Zheng, Li; Xing, Wen-Jing; Zhou, Hao; Cao, Dong-Sun; Zhang, Tong-Cun

    2014-12-01

    Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-κB (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1. Copyright © 2014 Elsevier Inc. All rights reserved.