Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.

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Ma, Xiaojuan; Feng, Yingmei

2016-07-19

As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein receptors to control cholesterol homeostasis. Deficiency of these receptors abrogates cellular cholesterol efflux, resulting in HSPC proliferation and differentiation in hypercholesterolemic mice. Reduction of the cholesterol level in the lipid rafts by infusion of reconstituted high-density lipoprotein (HDL) or its major apolipoprotein, apoA-I, reverses hypercholesterolemia-induced HSPC expansion. Apart from impaired cholesterol metabolism, inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis. These data indicate that the mechanisms underlying the effects of hypercholesterolemia on HSPC proliferation and differentiation could be multifaceted. Furthermore, dyslipidemia also regulates HSPC-neighboring cells, resulting in HSPC mobilization. In the article, we review how hypercholesterolemia evokes HSPC activation and mobilization directly or via its modification of BM microenvironment. We hope this review will bring light to finding key molecules to control HSPC expansion, inflammation, and atherosclerosis for the treatment of CVD.

Inflammation of vertebral bone associated with acute calcific tendinitis of the longus colli muscle

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Mihmanli, I.; Kanberoglu, K. [Dept. of Radiology, Istanbul Univ. (Turkey); Karaarslan, E. [Intermed Medical Center, Nisantasi, Istanbul (Turkey)

2001-12-01

We present a case of acute retropharyngeal calcific tendinitis with characteristic findings on radiographic, computed tomography, and magnetic resonance imaging (MRI). To our knowledge, this is the first acute retropharyngeal calcific tendinitis report having inflammation of both the vertebra itself and the longus colli muscle diagnosed on MRI. In patients with neck pain, acute retropharyngeal calcific tendinitis should be kept in mind in the differential diagnosis, even if these patients had vertebral pathological signals on MRI. (orig.)

Inflammation of vertebral bone associated with acute calcific tendinitis of the longus colli muscle

International Nuclear Information System (INIS)

Mihmanli, I.; Kanberoglu, K.; Karaarslan, E.

2001-01-01

We present a case of acute retropharyngeal calcific tendinitis with characteristic findings on radiographic, computed tomography, and magnetic resonance imaging (MRI). To our knowledge, this is the first acute retropharyngeal calcific tendinitis report having inflammation of both the vertebra itself and the longus colli muscle diagnosed on MRI. In patients with neck pain, acute retropharyngeal calcific tendinitis should be kept in mind in the differential diagnosis, even if these patients had vertebral pathological signals on MRI. (orig.)

Intracranial atherosclerosis and inflammation: Lessons from the East and the West

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Juan F Arenillas

2015-01-01

Full Text Available Intracranial atherosclerosis (ICAS is a major cause of ischemic stroke worldwide. Patients affected by this disease have a high risk of suffering further ischemic strokes and other major vascular events despite the best medical therapy available. However, identification of factors that characterize a high-risk ICAS patient is a clinical problem that is yet to be solved. Inflammation is known to play a crucial role in all the stages of atherosclerosis affecting extracranial arterial beds but its role in ICAS is not firmly established. Circulating inflammatory biomarkers may represent a valuable tool to assess the importance of systemic and local (intraplaque inflammation in ICAS pathogenesis. In this article, we have reviewed studies with inflammatory biomarkers performed in symptomatic and asymptomatic ICAS patients published in the recent literature. Their findings strongly support the hypothesis that inflammation determines the risk of progression and complication of symptomatic ICAS.

Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice

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Daniel A. Giles

2016-11-01

Full Text Available Objectives: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease. The lack of a physiologically relevant experimental model of atherosclerosis has hindered the understanding of mechanisms regulating disease development and progression as well as the development of translational therapies. Recent evidence suggests that housing mice within their thermoneutral zone profoundly alters murine physiology, including both metabolic and immune processes. We hypothesized that thermoneutral housing would allow for augmentation of atherosclerosis induction and progression in mice. Methods: ApoE−/− and WT mice were housed at either standard (TS or thermoneutral (TN temperatures and fed either a chow or obesogenic “Western” diet. Analysis included quantification of (i obesity and obesity-associated downstream sequelae, (ii the development and progression of atherosclerosis, and (iii inflammatory gene expression pathways related to atherosclerosis. Results: Housing mice at TN, in combination with an obesogenic “Western” diet, profoundly augmented obesity development, exacerbated atherosclerosis in ApoE−/− mice, and initiated atherosclerosis development in WT mice. This increased disease burden was associated with altered lipid profiles, including cholesterol levels and fractions, and increased aortic plaque size. In addition to the mild induction of atherosclerosis, we similarly observed increased levels of aortic and white adipose tissue inflammation and increased circulating immune cell expression of pathways

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

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Cohoon, Kevin P; Criqui, Michael H; Budoff, Matthew J; Lima, Joao A; Blaha, Michael J; Decker, Paul A; Durazo, Ramon; Liu, Kiang; Kramer, Holly

2018-05-01

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease

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Thomsen, Stine B; Rathcke, Camilla N; Zerahn, Bo

2010-01-01

. In the present study levels of markers of calcification (MGP) and inflammation (YKL-40, hsCRP) were evaluated in patients with T2 D and/or ischemic heart disease (IHD). MATERIALS AND METHODS: The study population consisted of 1) patients with T2D (n = 45); 2) patients with IHD (n = 37); patients with both T2D......OBJECTIVE AND DESIGN: Low grade inflammation is of pathogenic importance in atherosclerosis and in the development of cardiovascular disease (CVD) and type 2 diabetes (T2D). Matrix GLA protein (MGP), an inhibitor of medial calcification of arteries, is increased in patients with atherosclerosis...... and IHD (n = 20) and 4) healthy controls (n = 20). Biochemical parameters were measured in venous blood samples. RESULTS: Levels of MGP, YKL-40 and hsCRP were increased in patients with IHD and/or T2D (p T2D and IHD had higher MGP levels (p

Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis.

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Cavaco, Sofia; Viegas, Carla S B; Rafael, Marta S; Ramos, Acácio; Magalhães, Joana; Blanco, Francisco J; Vermeer, Cees; Simes, Dina C

2016-03-01

Osteoarthritis (OA) is a whole-joint disease characterized by articular cartilage loss, tissue inflammation, abnormal bone formation and extracellular matrix (ECM) mineralization. Disease-modifying treatments are not yet available and a better understanding of osteoarthritis pathophysiology should lead to the discovery of more effective treatments. Gla-rich protein (GRP) has been proposed to act as a mineralization inhibitor and was recently shown to be associated with OA in vivo. Here, we further investigated the association of GRP with OA mineralization-inflammation processes. Using a synoviocyte and chondrocyte OA cell system, we showed that GRP expression was up-regulated following cell differentiation throughout ECM calcification, and that inflammatory stimulation with IL-1β results in an increased expression of COX2 and MMP13 and up-regulation of GRP. Importantly, while treatment of articular cells with γ-carboxylated GRP inhibited ECM calcification, treatment with either GRP or GRP-coated basic calcium phosphate (BCP) crystals resulted in the down-regulation of inflammatory cytokines and mediators of inflammation, independently of its γ-carboxylation status. Our results strengthen the calcification inhibitory function of GRP and strongly suggest GRP as a novel anti-inflammatory agent, with potential beneficial effects on the main processes responsible for osteoarthritis progression. In conclusion, GRP is a strong candidate target to develop new therapeutic approaches.

Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: A combined transcriptomics and metabolomics analysis

NARCIS (Netherlands)

Kleemann, R.; Verschuren, L.; Erk, M.J. van; Nikolsky, Y.; Cnubben, N.H.P.; Verheij, E.R.; Smilde, A.K.; Hendriks, H.F.J.; Zadelaar, A.S.M.; Smith, G.J.; Kaznacheev, V.; Nikolskaya, T.; Melnikov, A.; Hurt-Camejo, E.; Greef, J. van der; Ommen, B. van; Kooistra, T.

2007-01-01

Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we

Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5.

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Kurnatowska, Ilona; Grzelak, Piotr; Masajtis-Zagajewska, Anna; Kaczmarska, Magdalena; Stefańczyk, Ludomir; Vermeer, Cees; Maresz, Katarzyna; Nowicki, Michał

2015-01-01

Observational studies have shown that high dietary intake of vitamin K2 is associated with reduced risk of coronary vascular disease and vascular calcification. We assessed the effect of vitamin K2 substitution on the progression of atherosclerosis and calcification in nondialyzed patients with CKD stages 3-5. The study included 42 nondialyzed patients with CKD. The following measurements were taken at baseline and after 270 ±12 days of supplementation with vitamin K2 at a dose of 90 μg (menaquinone, MK-7) together with 10 μg of cholecalciferol (K+D group) or 10 μg of cholecalciferol (group D): common carotid intima-media thickness (CCA-IMT), coronary artery calcification score (CACS), basic biochemical parameters, lipids, and calcification modulators: matrix Gla protein (MGP), desphosphorylated-uncarboxylated MGP (dp-ucMGP), osteoprotegerin (OPG), fetuin A, osteocalcin (OC), and fibroblast growth factor 23. The increase of CCA-IMT was significantly lower in the K+D group compared with the D group: from 0.95 ±0.2 mm to 1.01 ±0.3, P = 0.003 vs from 1.02 ±0.2 mm to 1.16 ±0.3, P = 0.003 (ΔCCA-IMT, 0.06 ±0.08 vs 0.136 ±0.05 mm, P = 0.005, respectively). The increase in CACS was slightly lower in the K+D group than in the D group (ΔCACS, 58.1 ±106.5 AU vs 74.4 ±127.1 AU, P = 0.7). In the K+D group, a significant decrease in the level of dp-ucMGP and total OC was observed. A 270-day course of vitamin K2 administration in patients with CKD stages 3-5 may reduce the progression of atherosclerosis, but does not significantly affect the progression of calcification. Vitamin K2 significantly changes the levels of calcification promoters and inhibitors: dp-ucMGP, OC, and OPG.

Serum phosphate is associated with aortic valve calcification in the Multi-ethnic Study of Atherosclerosis (MESA).

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Linefsky, Jason P; O'Brien, Kevin D; Sachs, Michael; Katz, Ronit; Eng, John; Michos, Erin D; Budoff, Matthew J; de Boer, Ian; Kestenbaum, Bryan

2014-04-01

This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC). Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease. We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1 mg/dL increment, 95% confidence incidence: 1.1 to 1.5, pAVC. Average follow-up CT evaluation was 2.4 years (range 0.9-4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile. Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted. Published by Elsevier Ireland Ltd.

Atorvastatin Protects Vascular Smooth Muscle Cells From TGF-β1-Stimulated Calcification by Inducing Autophagy via Suppression of the β-Catenin Pathway

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Demin Liu

2014-01-01

Full Text Available Background: Arterial calcification is a major event in the progression of atherosclerosis. It is reported that statins exhibit various protective effects against vascular smooth muscle cell (VSMC inflammation and proliferation in cardiovascular remodeling. Although statins counteract atherosclerosis, the molecular mechanisms of statins on the calcium release from VSMCs have not been clearly elucidated. Methods: Calcium content of VSMCs was measured using enzyme-linked immunosorbent assay (ELISA. The expression of proteins involved in cellular transdifferentiation was analyzed by western blot. Cell autophagy was measured by fluorescence microscopic analysis for acridine orange staining and transmission electron microscopy analysis. The autophagic inhibitors (3-MA, chloroquine, NH4Cl and bafilomycin A1 and β-catenin inhibitor JW74 were used to assess the effects of atorvastatin on autophagy and the involvement of β-catenin on cell calcification respectively. Furthermore, cell transfection was performed to overexpress β-catenin. Results: In VSMCs, atorvastatin significantly suppressed transforming growth factor-β1 (TGF-β1-stimulated calcification, accompanied by the induction of autophagy. Downregulation of autophagy with autophagic inhibitors significantly suppressed the inhibitory effect of atorvastatin on cell calcification. Moreover, the beneficial effect of atorvastatin on calcification and autophagy was reversed by β-catenin overexpression. Conversely, JW74 supplement enhanced this effect. Conclusion: These data demonstrated that atorvastatin protect VSMC from TGF-β1-stimulated calcification by inducing autophagy through suppression of the β-catenin pathway, identifying autophagy induction might be a therapeutic strategy for use in vascular calcification.

A novel ultrasound-based vascular calcification score (CALCS) to detect subclinical atherosclerosis.

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Flore, R; Zocco, M A; Ainora, M E; Fonnesu, C; Nesci, A; Gasbarrini, A; Ponziani, F R

2018-02-01

To quantify non-coronary vascular calcifications (VC) in asymptomatic patients at low-intermediate cardiovascular risk by a new color Doppler ultrasound (DUS)-based score (the carotid, aortic, lower limbs calcium score, CALCs), and to correlate this score with classical parameters associated with cardiovascular risk [carotid intima media thickness (IMT), and arterial stiffness (AS)]. All consecutive asymptomatic patients who underwent a screening DUS of non-coronary circulation were evaluated and patients at low-intermediate cardiovascular risk were selected according to Framingham risk score (FRS). Among them, we enrolled 70 patients with US evidence of VC and 71 age, sex and FRS matched controls. The presence of VC was correlated with classical markers of cardiovascular risk, such as AS and intima-media thickness (IMT). AS, expressed as pulse wave velocity (PWV) and arterial distensibility, carotid IMT and CALCs were measured for both groups. AS and c-IMT were assessed by a new Radio-Frequency (RF) DUS-based method. CALCs was generated by our previously described B-mode DUS-based method according to number/size of VC in 11 non-coronary segments (range 0-33). Patients with VC presented higher AS and IMT values than controls (PWV 8.34±0.98 m/s vs. 6.74±0.68 m/s, p<0.0001; arterial distensibility 267±12 mm vs. 315±65 mm, p=0.001; IMT 687±132 mm vs. 572±91 mm, p<0.0001). Mean CALCs of patients with VC was 8.41±7.78. CALCs were significantly correlated with c-IMT (p<0.0001; r=0.3), PWV (p<0.0001; r=0.4) and arterial distensibility (p=0.002; r=-0.1). DUS-based CALCs is highly correlated with other validated markers of subclinical atherosclerosis, such as c-IMT and AS. Our results demonstrated the ability of CALCs to identify individual predictive factors beyond the traditional risk factors by quantifying an interesting and novel step of the atherogenic process. Future studies on larger series and with adequate follow up are necessary to confirm these results and

Decreased naive and increased memory CD4(+ T cells are associated with subclinical atherosclerosis: the multi-ethnic study of atherosclerosis.

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Nels C Olson

Full Text Available Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4(+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.We examined cross-sectional relationships of circulating CD4(+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA. Circulating CD4(+ naive cells were higher in women than men and decreased with age (all p-values <0.0001. European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005. Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05. Higher memory cells were associated with coronary artery calcification (CAC level in the overall population [β-Coefficient (95% confidence interval (CI  = 0.20 (0.03, 0.37]. Memory and naive (inversely cells were associated with common carotid artery intimal media thickness (CC IMT in European-Americans [memory: β =  0.02 (0.006, 0.04; naive: β = -0.02 (-0.004, -0.03].These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4(+ T cells, and with innate immunity (inflammation, in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate

Insights From Pre-Clinical and Clinical Studies on the Role of Innate Inflammation in Atherosclerosis Regression

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Karishma Rahman

2018-05-01

Full Text Available Atherosclerosis, the underlying cause of coronary artery (CAD and other cardiovascular diseases, is initiated by macrophage-mediated immune responses to lipoprotein and cholesterol accumulation in artery walls, which result in the formation of plaques. Unlike at other sites of inflammation, the immune response becomes maladaptive and inflammation fails to resolve. The most common treatment for reducing the risk from atherosclerosis is low density lipoprotein cholesterol (LDL-C lowering. Studies have shown, however, that while significant lowering of LDL-C reduces the risk of heart attacks to some degree, there is still residual risk for the majority of the population. We and others have observed “residual inflammatory risk” of atherosclerosis after plasma cholesterol lowering in pre-clinical studies, and that this phenomenon is clinically relevant has been dramatically reinforced by the recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS trial. This review will summarize the role of the innate immune system, specifically macrophages, in atherosclerosis progression and regression, as well as the pre-clinical and clinical models that have provided significant insights into molecular pathways involved in the resolution of plaque inflammation and plaque regression. Partnered with clinical studies that can be envisioned in the post-CANTOS period, including progress in developing targeted plaque therapies, we expect that pre-clinical studies advancing on the path summarized in this review, already revealing key mechanisms, will continue to be essential contributors to achieve the goals of dampening plaque inflammation and inducing its resolution in order to maximize the therapeutic benefits of conventional risk factor modifications, such as LDL-C lowering.

Cardiovascular calcification. An inflammatory disease

International Nuclear Information System (INIS)

New, S.E.P.; Aikawa, E.

2011-01-01

Cardiovascular calcification is an independent risk factor for cardiovascular morbidity and mortality. This disease of dysregulated metabolism is no longer viewed as a passive degenerative disease, but instead as an active process triggered by pro-inflammatory cues. Furthermore, a positive feedback loop of calcification and inflammation is hypothesized to drive disease progression in arterial calcification. Both calcific aortic valve disease and atherosclerotic arterial calcification may possess similar underlying mechanisms. Early histopathological studies first highlighted the contribution of inflammation to cardiovascular calcification by demonstrating the accumulation of macrophages and T lymphocytes in 'early' lesions within the aortic valves and arteries. A series of in vitro work followed, which gave a mechanistic insight into the stimulation of smooth muscle cells to undergo osteogenic differentiation and mineralization. The emergence of novel technology, in the form of animal models and more recently molecular imaging, has enabled accelerated progression of this field, by providing strong evidence regarding the concept of this disorder as an inflammatory disease. Although there are still gaps in our knowledge of the mechanisms behind this disorder, this review discusses the various studies that have helped form the concept of the inflammation-dependent cardiovascular calcification paradigm. (author)

Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice

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Bisgaard, Line S; Bosteen, Markus H; Fink, Lisbeth N

2016-01-01

Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosc......Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis...... aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX)). Uremic (n = 29) and sham-operated (n = 14) atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.......c. once daily) or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-), CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation...

Increased arterial inflammation in individuals with stage 3 chronic kidney disease

International Nuclear Information System (INIS)

Takx, Richard A.P.; MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Lavender, Zachary R.; Singh, Parmanand; Di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney; Mann, Jessica; Comley, Robert A.; Weber, Chek Ing Kiu; Tawakol, Ahmed

2016-01-01

While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using 18 F-FDG PET/CT in patients with CKD and in matched controls. This retrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed. Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 ± 0.49 vs. 2.16 ± 0.43; p = 0.002). Arterial SUV correlated inversely with eGFR (r = -0.299, p = 0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC). Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of cardiovascular

Increased arterial inflammation in individuals with stage 3 chronic kidney disease

Energy Technology Data Exchange (ETDEWEB)

Takx, Richard A.P. [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Lavender, Zachary R. [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Singh, Parmanand [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); New York Presbyterian Hospital, Weill Cornell Medical College, Division of Cardiology, New York, NY (United States); Di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney [Brigham and Women' s Hospital and Harvard Medical School, Division of Radiology, Department of Medicine, Boston, MA (United States); Mann, Jessica; Comley, Robert A.; Weber, Chek Ing Kiu [F. Hoffmann-La Roche Ltd., Basel (Switzerland); Tawakol, Ahmed [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Massachusetts General Hospital and Harvard Medical School, Cardiology Division, Boston, MA (United States); Massachusetts General Hospital, Boston, MA (United States)

2016-02-15

While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using {sup 18}F-FDG PET/CT in patients with CKD and in matched controls. This retrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed. Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 ± 0.49 vs. 2.16 ± 0.43; p = 0.002). Arterial SUV correlated inversely with eGFR (r = -0.299, p = 0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC). Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of

The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

DEFF Research Database (Denmark)

Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel

Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional......SUV) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree...

The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

DEFF Research Database (Denmark)

Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

2013-01-01

Objectives: Aging is an important independent determinant of plaque biology. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and calcification metabolism. Methods: Thirteen healthy volunteers without traditional cardiovascular risk factors were...... and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18-FDG and aortic Na-18F avidity. A second order polynomial regression established that aging is a predictor of the degree of aortic plaque inflammation (R = 0.524; F statistic = 4.93; P = 0...... data, a quadratic relationship appears to exist between aging and plaque inflammation. Furthermore, a quadratic relationship was observed between aging and plaque calcification metabolism. In line with these observations, a linear relationship was observed between atherosclerotic plaque inflammation...

Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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P Padmini S J Khedoe

Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

Molecular Imaging of Inflammation in Atherosclerosis

Science.gov (United States)

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

Periodontal disease is an independent predictor of intracardiac calcification.

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Pressman, Gregg S; Qasim, Atif; Verma, Nitin; Miyamae, Masami; Arishiro, Kumiko; Notohara, Yasuhiro; Crudu, Vitalie; Figueredo, Vincent M

2013-01-01

Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P = 0.024). There was no significant interaction by study site, race, or gender. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification.

Dietary fatty acids on aortic root calcification in mice with metabolic syndrome.

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Naranjo, Maria C; Bermudez, Beatriz; Garcia, Indara; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G; Montserrat-de la Paz, Sergio

2017-04-19

Metabolic syndrome (MetS) is associated with obesity, dyslipidemia, type 2 diabetes, and chronic low-grade inflammation. The aim of this study was to determine the role of high-fat low-cholesterol diets (HFLCDs) rich in SFAs (HFLCD-SFAs), MUFAs (HFLCD-MUFAs) or MUFAs plus omega-3 long-chain PUFAs (HFLCD-PUFAs) on vascular calcification by the modulation of the RANKL/RANK/OPG system in the aortic roots of Lep ob/ob LDLR -/- mice. Animals fed with HFLCD-SFAs had increased weight and a greater atheroma plaque size, calcification, and RANKL/CATHK expression in the aortic root than mice on MUFA-enriched diets, with an increasing OPG expression in the aortic roots of the latter. Our study demonstrates that compared to dietary SFAs, MUFAs from olive oil protect against atherosclerosis by interfering with vascular calcification via the RANKL/RANK/OPG system in the setting of MetS. These findings open opportunities for developing novel nutritional strategies with olive oil as the most important dietary source of MUFAs (notably oleic acid) to prevent cardiovascular complications in MetS.

Coronary atherosclerosis in sudden cardiac death: An autopsy study

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Sudha M

2009-10-01

Full Text Available Background: The incidence of ischemic heart disease (IHD has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. Materials and Methods: Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000um 2 were assessed. The statistical significance was estimated. Results and Conclusions: Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

Non-invasive assessment of coronary calcification

International Nuclear Information System (INIS)

Vliegenthart, Rozemarijn; Oei, Hok-Hay S.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jackqueline C. M.

2004-01-01

Electron-beam tomography (EBT) and multi-detector computed tomography (MDCT) enable the noninvasive assessment of coronary calcification. The amount of coronary calcification, as detected by EBT, has a close relation with the amount of coronary atherosclerosis, which is the substrate for the occurrence of myocardial infarction and sudden cardiac death. Calcification of the coronary arteries can be seen as a cumulative measure of life-time exposure to cardiovascular risk factors. Several studies have shown that the amount of coronary calcification is associated with the risk of coronary heart disease. Therefore, coronary calcification is a promising method for non-invasive detection of asymptomatic subjects at high risk of developing coronary heart disease. Whether measurement of coronary calcification also increases the predictive power of coronary events based on cardiovascular risk factors is topic of current research

Periodontal Disease Is an Independent Predictor of Intracardiac Calcification

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Gregg S. Pressman

2013-01-01

Full Text Available Background. Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. Hypothesis. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Methods. Cross-sectional study at two sites (USA and Japan involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Results. Fifty-six of 73 subjects (77% had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2. In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P=0.001 was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P=0.024. There was no significant interaction by study site, race, or gender. Conclusions. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification.

Calcific aortic valve damage as a risk factor for cardiovascular events

International Nuclear Information System (INIS)

Wasilewski, Jarosław; Mirota, Kryspin; Wilczek, Krzysztof; Głowacki, Jan; Poloński, Lech

2012-01-01

Aortic valve calcification (AVC) is a common disease of the elderly. It is a progressive disease ranging from mild valve thickening to severe calcification with aortic valve stenosis. Risk factors for AVC are similar to those for atherosclerosis: age, gender, hypercholesterolemia, diabetes, hypertension, smoking and renal failure. AVC shares many similarities to atherosclerosis, including inflammatory cells and calcium deposits, and correlates with coronary plaque burden. Presence of AVC is associated with increased risk of adverse cardiovascular events. The objective for this review is to discuss the clinical features, natural history and prognostic significance of aortic valve calcifications, including mechanical and hemodynamic factors of flow distribution

Breast arterial calcification and risk of carotid atherosclerosis: Focusing on the preferentially affected layer of the vessel wall

International Nuclear Information System (INIS)

Sedighi, Nahid; Radmard, Amir Reza; Radmehr, Ali; Hashemi, Pari; Hajizadeh, Abdolmahmoud; Taheri, Amir Pejman Hashemi

2011-01-01

Objective: To assess the relationship between breast arterial calcification (BAC) detected on screening mammography and atherosclerosis of carotid arteries considering the most likely involved layer of the arterial wall. Materials and methods: A total of 537 consecutive women who underwent screening mammography were enrolled in this study. Seventy-nine subjects having BAC, aged 46-75 years, and 125 age-matched controls from those without BAC were selected for ultrasound examination of carotid arteries assessing intima-media thickness (IMT) and plaque presence. Participants were divided into three groups of risk including, low-risk: IMT 0.8 mm and/or plaque. Risk factors for atherosclerosis were obtained from medical records for independent effects. Results: BAC was present in 14.7% of mammograms. According to multivariable logistic regression analyses, significant association was identified between the carotid atherosclerosis risk and presence of BAC. Compared to women with IMT 0.8 mm had OR (95% CI) of 4.88 (1.47-16.16) and 23.36 (4.54-120.14), respectively. The OR (95% CI) for carotid plaque was 3.13 (1.3-7.57). There was no interaction between IMT category and plaque. Significant associations were also detected with postmenopausal duration (P = 0.02) and hypertension (P = 0.004). Conclusion: The risk of carotid atherosclerosis increases with the presence of BAC. Women with BAC are more likely to have thicker IMT than plaque, which could be attributed to the preferentially similar affected layer of media causing thick IMT rather than plaque.

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

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Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

2018-01-01

Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

Science.gov (United States)

Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

2015-01-28

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The relationship between aortic calcification on chest radiography and ionizing radiation in RERF's Adult Health Study

International Nuclear Information System (INIS)

Yamada, M.; Suzuki, G.; Masunari, N.; Kasagi, F.

2003-01-01

Aortic calcification has been reported to be an indicator of atherosclerosis and a predictor of coronary heart disease. However, the relationship between aortic calcification and conventional coronary risk factors or recently reported coronary risk factors including ionizing radiation, which is one kind of oxidative stress, has not been established. Objective: To investigate the relationship between aortic calcification and ionizing radiation in a longitudinal study design. The study cohort comprises the Radiation Effects Research Foundation's Adult Health Study participants which include atomic-bomb survivors and sex- and age-matched controls. A total of 522 men and 938 women identified as not having aortic calcification based on plain chest X-ray examinations at baseline examination between 1991 and 1993 were assessed regarding the presence of aortic calcification (mild/ severe calcification) about 10 years later. The relationship between cumulative incidence of aortic calcification and atomic-bomb radiation was analyzed using logistic regression analysis after adjusting for sex, age, and other coronary risk factors such as blood pressure, total cholesterol, and inflammation markers. Age-adjusted cumulative incidence of aortic calcification showed a possible increase with atomic-bomb radiation dose for both total aortic calcification and severe aortic calcification. But after adjusting for other coronary risk factors such as smoking, SBP, total cholesterol, HDL-cholesterol, hemoglobin A1c, and leukocyte neutropils, radiation dose was not a significant predictor of cumulative incidence of severe aortic calcification. Age-adjusted increase of cumulative incidence of aortic calcification with atomic-bomb radiation dose suggests ionizing radiation is one predictor of atheroscelerosis. Nevertheless, its predictive impact may not be as significant as conventional coronary risk factors

A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis.

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Takashi K Ito

Full Text Available Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-κB signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-κB suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses.

Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification

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Sinee Disthabanchong

2018-01-01

Full Text Available Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23 which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs. In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.

Association of mitral annulus calcification, aortic valve calcification with carotid intima media thickness

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Scuteri Angelo

2004-10-01

Full Text Available Abstract Background Mitral annular calcification (MAC and aortic annular calcification (AVC may represent a manifestation of generalized atherosclerosis in the elederly. Alterations in vascular structure, as indexed by the intima media thickness (IMT, are also recognized as independent predictors of adverse cardiovascular outcomes. Aim To examine the relationship between the degree of calcification at mitral and/or aortic valve annulus and large artery structure (thickness. Methods We evaluated 102 consecutive patients who underwent transthoracic echocardiography and carotid artery echoDoppler for various indications; variables measured were: systemic blood pressure (BP, pulse pressure (PP=SBP-DBP, body mass index (BMI, fasting glucose, total, HDL, LDL chlolesterol, triglycerides, cIMT. The patients were divided according to a grading of valvular/annular lesions independent scores based on acoustic densitometry: 1 = annular/valvular sclerosis/calcification absence; 2 = annular/valvular sclerosis; 3 = annular calcification; 4 = annular-valvular calcification; 5 = valvular calcification with no recognition of the leaflets. Results Patient score was the highest observed for either valvular/annulus. Mean cIMT increased linearly with increasing valvular calcification score, ranging from 3.9 ± 0.48 mm in controls to 12.9 ± 1.8 mm in those subjects scored 5 (p 0.0001. Conclusion MAC and AVC score can identify subgroups of patients with different cIMT values which indicate different incidence and prevalence of systemic artery diseases. This data may confirm MAC-AVC as a useful important diagnostic parameter of systemic atherosclerotic disease.

Arterial calcification: friend or foe?

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Nicoll, Rachel; Henein, Michael Y

2013-07-31

There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Breast arterial calcification and risk of carotid atherosclerosis: Focusing on the preferentially affected layer of the vessel wall

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Sedighi, Nahid, E-mail: nsedighi@sina.tums.ac.ir [Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences. North Kargar Ave., Tehran 14114 (Iran, Islamic Republic of); Radmard, Amir Reza, E-mail: radmard@ams.ac.ir [Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences. North Kargar Ave., Tehran 14114 (Iran, Islamic Republic of); Radmehr, Ali, E-mail: radmehr@sina.tums.ac.ir [Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences. North Kargar Ave., Tehran 14114 (Iran, Islamic Republic of); Hashemi, Pari, E-mail: phtums@yahoo.com [Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences. North Kargar Ave., Tehran 14114 (Iran, Islamic Republic of); Hajizadeh, Abdolmahmoud, E-mail: mroomezi@yahoo.com [Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences. North Kargar Ave., Tehran 14114 (Iran, Islamic Republic of); Taheri, Amir Pejman Hashemi, E-mail: hashemip@sina.tums.ac.ir [Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences. North Kargar Ave., Tehran 14114 (Iran, Islamic Republic of)

2011-08-15

Objective: To assess the relationship between breast arterial calcification (BAC) detected on screening mammography and atherosclerosis of carotid arteries considering the most likely involved layer of the arterial wall. Materials and methods: A total of 537 consecutive women who underwent screening mammography were enrolled in this study. Seventy-nine subjects having BAC, aged 46-75 years, and 125 age-matched controls from those without BAC were selected for ultrasound examination of carotid arteries assessing intima-media thickness (IMT) and plaque presence. Participants were divided into three groups of risk including, low-risk: IMT < 0.6 mm without plaque, medium-risk: 0.6 mm {<=} IMT {<=} 0.8 mm without plaque and high-risk: IMT > 0.8 mm and/or plaque. Risk factors for atherosclerosis were obtained from medical records for independent effects. Results: BAC was present in 14.7% of mammograms. According to multivariable logistic regression analyses, significant association was identified between the carotid atherosclerosis risk and presence of BAC. Compared to women with IMT < 0.6 mm, those with 0.6 mm {<=} IMT{<=} 0.8 mm and IMT > 0.8 mm had OR (95% CI) of 4.88 (1.47-16.16) and 23.36 (4.54-120.14), respectively. The OR (95% CI) for carotid plaque was 3.13 (1.3-7.57). There was no interaction between IMT category and plaque. Significant associations were also detected with postmenopausal duration (P = 0.02) and hypertension (P = 0.004). Conclusion: The risk of carotid atherosclerosis increases with the presence of BAC. Women with BAC are more likely to have thicker IMT than plaque, which could be attributed to the preferentially similar affected layer of media causing thick IMT rather than plaque.

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery

OpenAIRE

Kockelkoren, Remko; Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L. A. W.; Verdoorn, Daphne; Mali, Willem P. Th. M.; Hendrikse, Jeroen; Koek, Huiberdina L.; de Jong, Pim A.; De Vis, Jill B.

2017-01-01

BACKGROUND: Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore...

Thoracic aorta calcification but not inflammation is associated with increased cardiovascular disease risk: results of the CAMONA study

Energy Technology Data Exchange (ETDEWEB)

Blomberg, Bjoern A. [Odense University Hospital, Department of Nuclear Medicine, Odense C (Denmark); University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Jong, Pim A. de; Lam, Marnix G.E.; Mali, Willem P.T.M. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Thomassen, Anders [Odense University Hospital, Department of Nuclear Medicine, Odense C (Denmark); Vach, Werner [University Medical Center Freiburg, Clinical Epidemiology, Institute of Medical Biometry and Medical Informatics, Freiburg (Germany); Olsen, Michael H. [Odense University Hospital, The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology, Center for Individualized Medicine in Arterial Diseases, Odense (Denmark); Narula, Jagat [Mount Sinai Hospital, Icahn School of Medicine, New York, NY (United States); Alavi, Abass [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Hoeilund-Carlsen, Poul F. [Odense University Hospital, Department of Nuclear Medicine, Odense C (Denmark); University of Southern Denmark, Institute of Clinical Research, Odense (Denmark)

2017-02-15

Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease (CVD). In this study we investigated the relationship between CVD risk and arterial inflammation ({sup 18}F-FDG PET/CT imaging), vascular calcification metabolism (Na{sup 18}F PET/CT imaging), and vascular calcium burden (CT imaging) of the thoracic aorta in a population at low CVD risk. Study participants underwent blood pressure measurements, blood analyses, and {sup 18}F-FDG and Na{sup 18}F PET/CT imaging. In addition, the 10-year risk for development of CVD, based on the Framingham risk score (FRS), was estimated. CVD risk was compared across quartiles of thoracic aorta {sup 18}F-FDG uptake, Na{sup 18}F uptake, and calcium burden on CT. A total of 139 subjects (52 % men, mean age 49 years, age range 21 - 75 years, median FRS 6 %) were evaluated. CVD risk was, on average, 3.7 times higher among subjects with thoracic aorta Na{sup 18}F uptake in the highest quartile compared with those in the lowest quartile of the distribution (15.5 % vs. 4.2 %; P < 0.001). CVD risk was on average, 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution (18.0 % vs. 4.9 %; P < 0.001). CVD risk was similar in subjects in all quartiles of thoracic aorta {sup 18}F-FDG uptake. Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta, but not with arterial inflammation. (orig.)

Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection

Science.gov (United States)

Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

2016-01-01

Vascular calcification results in stiffening of the aorta and is associated with hypertension and atherosclerosis. Atherogenesis is a complex, multifactorial, and systemic process; the result of a number of factors, each operating simultaneously at several spatial and temporal scales. The ability to predict sites of atherogenesis would be of great use to clinicians in order to improve diagnostic and treatment planning. In this paper, we present a mathematical model as a tool to understand why atherosclerotic plaque and calcifications occur in specific locations. This model is then used to analyze vascular calcification and atherosclerotic areas in an aortic dissection patient using a mechanistic, multi-scale modeling approach, coupling patient-specific, fluid-structure interaction simulations with a model of endothelial mechanotransduction. A number of hemodynamic factors based on state-of-the-art literature are used as inputs to the endothelial permeability model, in order to investigate plaque and calcification distributions, which are compared with clinical imaging data. A significantly improved correlation between elevated hydraulic conductivity or volume flux and the presence of calcification and plaques was achieved by using a shear index comprising both mean and oscillatory shear components (HOLMES) and a non-Newtonian viscosity model as inputs, as compared to widely used hemodynamic indicators. The proposed approach shows promise as a predictive tool. The improvements obtained using the combined biomechanical/biochemical modeling approach highlight the benefits of mechanistic modeling as a powerful tool to understand complex phenomena and provides insight into the relative importance of key hemodynamic parameters. PMID:27445834

Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography.

Science.gov (United States)

Utsunomiya, Hiroto; Yamamoto, Hideya; Kunita, Eiji; Kitagawa, Toshiro; Ohashi, Norihiko; Oka, Toshiharu; Yamazato, Ryo; Horiguchi, Jun; Kihara, Yasuki

2010-11-01

We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (pNCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of tocopherol on atherosclerosis, vascular function, and inflammation in apolipoprotein E knockout mice with subtotal nephrectomy.

Science.gov (United States)

Shing, Cecilia M; Fassett, Robert G; Peake, Jonathan M; Coombes, Jeff S

2014-12-01

Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E(-/-) mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease. Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol). Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10(-7) M to 3 × 10(-5) M (P tocopherol reduced systemic concentrations of IL-6 (P tocopherol also reduced MCP-1 (P tocopherol supplementation when compared to normal chow (P Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E(-/-) mouse with CKD. © 2014 John Wiley & Sons Ltd.

A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

Science.gov (United States)

Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2016-02-01

Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

Inflammasomes and Atherosclerosis

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S. Vallurupalli, MD

2016-09-01

Full Text Available Inflammation plays an important role in atherosclerosis. Inflammasomes play a crucial role in innate immunity, which mediates the body’s response to various pathogens. Of the different types of inflammasomes, NLRP3 has been implicated in atherosclerosis through the production of proinflammatory cytokines, IL-1β and IL-18. This review describes the role of the NLRP3 inflammasome in atherosclerosis and discusses potential therapeutic targets in the inflammasome pathway.

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery

NARCIS (Netherlands)

Kockelkoren, Remko; Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L A W; Verdoorn, Daphne; Mali, Willem P Th M; Hendrikse, Jeroen; Koek, Huiberdina L; de Jong, Pim A; De Vis, Jill B

2017-01-01

BACKGROUND: Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial

Periodontal Pathogens and Atherosclerosis: Implications of Inflammation and Oxidative Modification of LDL

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Tomoko Kurita-Ochiai

2014-01-01

Full Text Available Inflammation is well accepted to play a crucial role in the development of atherosclerotic lesions, and recent studies have demonstrated an association between periodontal disease and cardiovascular disease. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, causative agents of destructive chronic inflammation in the periodontium, can accelerate atheroma deposition in animal models. Emerging evidence suggests that vaccination against virulence factors of these pathogens and anti-inflammatory therapy may confer disease resistance. In this review, we focus on the role of inflammatory mechanisms and oxidative modification in the formation and activation of atherosclerotic plaques accelerated by P. gingivalis or A. actinomycetemcomitans in an ApoE-deficient mouse model and high-fat-diet-fed mice. Furthermore, we examine whether mucosal vaccination with a periodontal pathogen or the anti-inflammatory activity of catechins can reduce periodontal pathogen-accelerated atherosclerosis.

Relationship of aortic valve calcification with coronary artery calcium severity: the Multi-Ethnic Study of Atherosclerosis (MESA).

Science.gov (United States)

Nasir, Khurram; Katz, Ronit; Al-Mallah, Mouaz; Takasu, Junichiro; Shavelle, David M; Carr, Jeffery J; Kronmal, Richard; Blumenthal, Roger S; O'Brien, Kevin; Budoff, Matthew J

2010-01-01

Aortic valve calcification (AVC) and atherosclerosis share causative and pathologic features. We evaluated the relationship between AVC and coronary artery calcium (CAC) severity in the Multi-Ethnic Study of Atherosclerosis (MESA). Men and women aged 45-84 years (n=6809; mean age, 62 years) were studied. The presence and burden of AVC and CAC were determined by noncontrast cardiac computed tomography. Relative risk regression was used to model the probability of AVC as a function of CAC > 0 as well as CAC categories (0, 1-99, 100-399, and > or = 400) with the reference group being CAC=0. The prevalence of AVC and CAC was 13% and 50%, respectively. Among those without CAC, the prevalence of AVC was 5% and increased across levels of CAC severity such that 14%, 25%, and 38% had AVC with increasing CAC scores of 1-99, 100-399, and > or = 400, respectively (P for trendAVC among those with mild CAC (1-99) was 1.83 (95% CI, 1.45-2.31) and increased to 3.36 (95% CI, 2.56-4.42) for CAC > or = 400. Similar statistically significant increased risk of AVC was found when CAC was assessed as a continuous variable. Our study shows that AVC is independently associated with increasing severity of CAC. 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Inflammation and immune system interactions in atherosclerosis

NARCIS (Netherlands)

Legein, Bart; Temmerman, Lieve; Biessen, Erik A. L.; Lutgens, Esther

2013-01-01

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall.

Associations of Cigarette Smoking With Subclinical Inflammation and Atherosclerosis: ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health).

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Kianoush, Sina; Yakoob, Mohammad Yawar; Al-Rifai, Mahmoud; DeFilippis, Andrew P; Bittencourt, Marcio S; Duncan, Bruce B; Bensenor, Isabela M; Bhatnagar, Aruni; Lotufo, Paulo A; Blaha, Michael J

2017-06-24

There is a need to identify sensitive biomarkers of early tobacco-related cardiovascular disease. We examined the association of smoking status, burden, time since quitting, and intensity, with markers of inflammation and subclinical atherosclerosis. We studied 14 103 participants without clinical cardiovascular disease in ELSA-Brasil (Brazilian Longitudinal Study of Adult Health). We evaluated baseline cross-sectional associations between smoking parameters and inflammation (high-sensitivity C-reactive protein [hsCRP]) and measures of subclinical atherosclerosis (carotid intima-media thickness, ankle-brachial index, and coronary artery calcium [CAC]). The cohort included 1844 current smokers, 4121 former smokers, and 8138 never smokers. Mean age was 51.7±8.9 years; 44.8% were male. After multivariable adjustment, compared with never smokers, current smokers had significantly higher levels of hsCRP (β=0.24, 0.19-0.29 mg/L; P media thickness (β=0.03, 0.02-0.04 mm; P 0 (odds ratio: 1.83; 95% confidence interval, 1.46-2.30; P media thickness levels and odds of ankle-brachial index ≤1.0 and CAC >0 were lower with increasing time since quitting ( P 0 ( P =0.03) after adjusting for duration of smoking. Strong associations were observed between smoking status, burden, and intensity with inflammation (hsCRP) and subclinical atherosclerosis (carotid intima-media thickness, ankle-brachial index, CAC). These markers of early cardiovascular disease injury may be used for the further study and regulation of traditional and novel tobacco products. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort

DEFF Research Database (Denmark)

Fernández-Friera, Leticia; Peñalvo, José L; Fernández-Ortiz, Antonio

2015-01-01

age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque...

Heme oxygenase-1, oxidation, inflammation and atherosclerosis

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Jesus A Araujo

2012-07-01

Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

Alloxan-induced diabetes exacerbates coronary atherosclerosis and calcification in Ossabaw miniature swine with metabolic syndrome.

Science.gov (United States)

Badin, Jill K; Kole, Ayeeshik; Stivers, Benjamin; Progar, Victor; Pareddy, Anisha; Alloosh, Mouhamad; Sturek, Michael

2018-03-09

There is a preponderance of evidence implicating diabetes with increased coronary artery disease (CAD) and calcification (CAC) in human patients with metabolic syndrome (MetS), but the effect of diabetes on CAD severity in animal models remains controversial. We investigated whether diabetes exacerbates CAD/CAC and intracellular free calcium ([Ca 2+ ] i ) dysregulation in the clinically relevant Ossabaw miniature swine model of MetS. Sixteen swine, eight with alloxan-induced diabetes, were fed a hypercaloric, atherogenic diet for 6 months. Alloxan-induced pancreatic beta cell damage was examined by immunohistochemical staining of insulin. The metabolic profile was confirmed by body weight, complete blood panel, intravenous glucose tolerance test (IVGTT), and meal tolerance test. CAD severity was assessed with intravascular ultrasound and histology. [Ca 2+ ] i handling in coronary smooth muscle (CSM) cells was assessed with fura-2 ratiometric imaging. Fasting and post-prandial blood glucose, total cholesterol, and serum triglycerides were elevated in MetS-diabetic swine. This group also exhibited hypoinsulinemia during IVGTT and less pancreatic beta cell mass when compared to lean and MetS-nondiabetic swine. IVUS analysis revealed that MetS-diabetic swine had greater percent wall coverage, percent plaque burden, and calcium index when compared to lean and MetS-nondiabetic swine. Fura-2 imaging of CSM [Ca 2+ ] i revealed that MetS-nondiabetic swine exhibited increased sarcoplasmic reticulum Ca 2+ store release and Ca 2+ influx through voltage-gated Ca 2+ channels compared to lean swine. MetS-diabetic swine exhibited impaired Ca 2+ efflux. Diabetes exacerbates coronary atherosclerosis and calcification in Ossabaw miniature swine with MetS, accompanied by progression of [Ca 2+ ] i dysregulation in advanced CAD/CAC. These results recapitulate increased CAD in humans with diabetes and establish Ossabaw miniature swine as an animal model for future Met

The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

DEFF Research Database (Denmark)

Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

2013-01-01

prospectively assessed by 18-FDG (inflammation) and Sodium 18-Fluoride (Na-18F) (calcification metabolism) PET CT imaging. Global aortic uptake of 18-FDG and Na-18F was quantified by subtracting the blood pool SUVmean from the aortic SUVmax (cSUV) [maximum SUVaorta - mean SUVblood pool]. Calculating regression...

Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region

International Nuclear Information System (INIS)

Dragano, Nico; Hoffmann, Barbara; Stang, Andreas; Moebus, Susanne; Verde, Pablo E.; Weyers, Simone; Moehlenkamp, Stefan; Schmermund, Axel; Mann, Klaus; Joeckel, Karl-Heinz; Erbel, Raimund; Siegrist, Johannes

2009-01-01

Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45-75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease

Calcific Uremic Arteriolopathy: Pathophysiology, Reactive Oxygen Species and Therapeutic Approaches

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Kurt M. Sowers

2010-01-01

Full Text Available Calcific uremic arteriolopathy (CUA/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.

Ten-year trends in coronary calcification in individuals without clinical cardiovascular disease in the multi-ethnic study of atherosclerosis.

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Diane E Bild

Full Text Available Coronary heart disease (CHD incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known.To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC prevalence in a population over 10 years, we measured CAC using computed tomography (CT and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55-84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000-02, 50.4% in 2003-04, 60.0% is 2005-06, 57.4% in 2007-08, and 61.3% in 2010-12 (p for trend <0.001. The trend was strongest among African Americans aged 55-64 [prevalence ratio for 2010-12 vs. 2000-02, 1.59 (95% confidence interval 1.06, 2.39; p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence.There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

Science.gov (United States)

Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

Incidental internal carotid artery calcifications on temporal bone CT in children

International Nuclear Information System (INIS)

Koch, Bernadette; Jones, Blaise; Blackham, Aaron

2007-01-01

Incidental internal carotid artery (ICA) calcifications are occasionally noted on CT images of the brain and temporal bone. In adults, incidental calcifications have been correlated with increased incidence of hypercholesterolemia, cardiac disease, diabetes and carotid stenosis. To determine the incidence of incidental calcifications of the carotid siphon on temporal bone CT in children. We retrospectively reviewed 24 months of consecutive temporal bone CT examinations in children aged 18 years and younger. CT examinations on 663 patients were reviewed and the presence or absence of ICA calcifications was ranked as absent, questionable or definitive. In patients in whom definitive calcifications were identified, hospital charts were reviewed for evidence of diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia and chronic renal disease as potential causes of early atherosclerosis. Of the 663 patients, 25% had definitive calcifications within the wall of the ICA: 6% of children younger than 2 years and 28% of children 12-19 years of age. Incidentally noted ICA calcifications are a common finding on temporal bone CT in children, most likely a physiologic response to turbulent flow at natural bends in the artery rather than secondary to underlying disease predisposing to early atherosclerotic calcification. (orig.)

Incidental internal carotid artery calcifications on temporal bone CT in children

Energy Technology Data Exchange (ETDEWEB)

Koch, Bernadette; Jones, Blaise [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Blackham, Aaron [University of Cincinnati College of Medicine, Cincinnati, OH (United States)

2007-02-15

Incidental internal carotid artery (ICA) calcifications are occasionally noted on CT images of the brain and temporal bone. In adults, incidental calcifications have been correlated with increased incidence of hypercholesterolemia, cardiac disease, diabetes and carotid stenosis. To determine the incidence of incidental calcifications of the carotid siphon on temporal bone CT in children. We retrospectively reviewed 24 months of consecutive temporal bone CT examinations in children aged 18 years and younger. CT examinations on 663 patients were reviewed and the presence or absence of ICA calcifications was ranked as absent, questionable or definitive. In patients in whom definitive calcifications were identified, hospital charts were reviewed for evidence of diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia and chronic renal disease as potential causes of early atherosclerosis. Of the 663 patients, 25% had definitive calcifications within the wall of the ICA: 6% of children younger than 2 years and 28% of children 12-19 years of age. Incidentally noted ICA calcifications are a common finding on temporal bone CT in children, most likely a physiologic response to turbulent flow at natural bends in the artery rather than secondary to underlying disease predisposing to early atherosclerotic calcification. (orig.)

Aluminum Chloride Pretreatment of Elastin Inhibits Elastolysis by Matrix Metalloproteinases and Leads to Inhibition of Elastin-Oriented Calcification

OpenAIRE

Bailey, Michael; Xiao, Hui; Ogle, Matthew; Vyavahare, Naren

2001-01-01

Calcification of elastin occurs in many pathological cardiovascular diseases including atherosclerosis. We have previously shown that purified elastin when subdermally implanted in rats undergoes severe calcification and aluminum chloride (AlCl3) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl3 pretreatment. Subdermal implantation of AlCl3-pretreated elas...

Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?

Science.gov (United States)

Azarsız, Elif; Karaca, Neslihan; Levent, Erturk; Kutukculer, Necil; Sozmen, Eser

2017-11-01

Background Common variable immunodeficiency is a rare clinically symptomatic primary immunodeficiency disorder which manifests a wide variability of symptoms, complications. Atherosclerosis in common variable immunodeficiency patients has not been investigated yet contrary to other severe clinical complications. We aimed to investigate the chitotriosidase enzyme's role as an inflammation and atherosclerosis marker in paediatric common variable immunodeficiency patients. Methods Common variable immunodeficiency patients (n = 24) and healthy controls (n = 23) evaluated for chitotriosidase activity with other inflammation markers (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and echocardiographic findings (carotid artery intima media thickness - cIMT, brachial artery flow-mediated vazodilatation - FMD%). Results In patients, the mean chitotriosidase activity (8.98 ± 6.28) was significantly higher than the controls (5.17 ± 3.42) ( P = 0.014). Chitotriosidase showed positive relation with hs-CRP ( P = 0.011) and SAA ( P = 0.011) but had no relation with ferritin ( P = 0.155), HDL ( P = 0.152) or LDL-cholesterol ( P = 0.380). Mean cIMT increased in patients compared with the controls ( P variable immunodeficiency patients demonstrated in vivo the presence of activated macrophages indicating ongoing inflammation. Echocardiographic diastolic functional deficiency, increased cIMT and decreased FMD% may be accepted as early atherosclerotic findings, but none of them showed relationship with chitotriosidase activities.

Cell Phenotype Transitions in Cardiovascular Calcification

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Luis Hortells

2018-03-01

Full Text Available Cardiovascular calcification was originally considered a passive, degenerative process, however with the advance of cellular and molecular biology techniques it is now appreciated that ectopic calcification is an active biological process. Vascular calcification is the most common form of ectopic calcification, and aging as well as specific disease states such as atherosclerosis, diabetes, and genetic mutations, exhibit this pathology. In the vessels and valves, endothelial cells, smooth muscle cells, and fibroblast-like cells contribute to the formation of extracellular calcified nodules. Research suggests that these vascular cells undergo a phenotypic switch whereby they acquire osteoblast-like characteristics, however the mechanisms driving the early aspects of these cell transitions are not fully understood. Osteoblasts are true bone-forming cells and differentiate from their pluripotent precursor, the mesenchymal stem cell (MSC; vascular cells that acquire the ability to calcify share aspects of the transcriptional programs exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a fully-differentiated vascular cell directly acquires the ability to calcify by the upregulation of osteogenic genes or, whether these vascular cells first de-differentiate into an MSC-like state before obtaining a “second hit” that induces them to re-differentiate down an osteogenic lineage. Addressing these questions will enable progress in preventative and regenerative medicine strategies to combat vascular calcification pathologies. In this review, we will summarize what is known about the phenotypic switching of vascular endothelial, smooth muscle, and valvular cells.

Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel.

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Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-08-19

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into "pieces of the puzzle" in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature.

Seasonal variation in thoracic vessel calcifications: Evidence from a chest computed tomography study

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Vehmas, Tapio; Leino-Arjas, Paeivi (Health and Work Ability, Finnish Inst. of Occupational Health, Helsinki (Finland)), e-mail: tapio.vehmas@ttl.fi; Hiltunen, Asta (Dept. of Radiology, Central Hospital of Laensi-Pohja, Kemi (Finland))

2010-01-15

Background: Cardiovascular disease incidence and mortality exhibit a winter peak and a summer trough, a fact that could have radiological manifestations. Purpose: To identify possible seasonal trends in the occurrence of thoracic vessel calcifications. Material and Methods: 505 male construction workers (aged 39-80 years) were each imaged once with chest spiral computed tomography (CT) during a 2-year period. Based on visual assessment of calcified plaques (0=no, 1=slight, 2=moderate, 3=extensive calcification), sum scores of atherosclerosis in coronary arteries, in the thoracic aorta, in the pre-cervical artery bases, and overall were constructed. The scores were regressed on the annual rank number of the CT day. Results: By using the cubic regression model, seasonal variation in calcified plaques in coronary arteries (P=0.003), in pre-cervical artery origins (P=0.015), and in the overall sum score (P=0.004) was observed. The peak occurred in January-February and the nadir in August. Depending on the model, about 2-3% of the variation in atherosclerotic calcifications could be explained by the season of imaging. Conclusion: The observed seasonal trend in calcifications parallels with mortality reports. Seasonal variations should be considered in atherosclerosis treatment studies. Confirmatory studies using modern imaging technology are needed in different countries and geographical locations, preferably with repeat imaging of the same individuals

Tortuosity and calcification of the splenic artery. More than an additional finding

International Nuclear Information System (INIS)

Golder, W.A.

2008-01-01

Tortuosity of the splenic artery and calcification of the vessel wall are typical additional findings on plain abdominal x-ray. The combination of both anomalies is common in elderly persons presenting without symptoms of splenic ischemia. Its pathogenesis is thought to be multifactorial. In infancy and childhood, the splenic artery is stretched in its entire course. A growing difference between the length of the vessel and the distance between its origin and the splenic hilum gives rise to tortuosity. The artery's proximal segment is involved more frequently and more severely than the distal one. The tortuous route of the vessel is accentuated by the direction of its major branches, which is roughly perpendicular to the main trajectory. Neither tortuosity nor calcification should be taken to be risk factors for the comparatively common splenic artery aneurysm. Calcific deposits are not confined to the media but are also detected in the intima of the vascular wall. Critical narrowings of the lumen arising on the calcium deposits are not observed. Calcifying atherosclerosis of the splenic artery is comparable to medial sclerosis of the peripheral arteries frequently noticed in diabetics and dialysis patients. Only the less important calcification of the intima may be attributed to mechanisms of the hydrohemodynamic theory of atherosclerosis. The spleen's blood storage capacity may contribute to the characteristic age-dependent alterations of the shape and course of the splenic artery. (orig.) [de

[Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

Science.gov (United States)

Kohara, Katsuhiko

2014-10-01

Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice

DEFF Research Database (Denmark)

Madsen, Marie; Hansen, Peter Riis; Nielsen, Lars Bo

2016-01-01

BACKGROUND: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought...... to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation. METHODS: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice. RESULTS: TPA led to localized...

Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

Science.gov (United States)

Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

2014-01-31

Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

Induction of calcification by serum depletion in cell culture: a model for focal calcification in aortas related to atherosclerosis

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Villar Maria T

2008-01-01

Full Text Available Abstract Background Since aortic calcification has been shown to initiate in the lower zone of well-thickened plaques (LZP adjacent to the aortic media of rabbits fed supplemental cholesterol diets, a restricted supply of serum to vascular cells could play a role in vascular calcification. This study was designed to use a cell culture model to support this hypothesis. Results Rabbit aortic smooth muscle cells were grown to confluence in a culture media containing 10 % fetal bovine serum (FBS. The confluent cells were then exposed to the media for 2 hrs with or without serum at a Ca × P ion product range of 4.5–9.4 mM2. In contrast to the cells cultured in the presence of FBS, confluent cells in its absence displayed marked mineral-positive alizarin red staining and infrared absorption of mineral phosphate. A kinetic parameter C1/2 was used to designate the concentration of serum or its protein constituents needed to reduce the deposition of Ca and P by half. The C1/2 for FBS and rabbit serum was 0.04–0.07 % The C1/2 value for rabbit serum proteins was 13.5 μg/ml corresponding to the protein concentration in 0.06 % of serum. This C1/2 was markedly smaller than 86.2 μg/ml for bovine serum albumin present in 0.37 % serum (p Conclusion The aortic smooth muscle cell culture model suggests that serum depletion may play a role in the initiation of aortic calcification. The serum exhibits remarkable ability to inhibit cell-mediated calcification.

Associations of Triiodothyronine Levels with Carotid Atherosclerosis and Arterial Stiffness in Hemodialysis Patients

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Kircelli, Fatih; Asci, Gulay; Carrero, Juan Jesus; Gungor, Ozkan; Demirci, Meltem Sezis; Ozbek, Suha Sureyya; Ceylan, Naim; Ozkahya, Mehmet; Toz, Huseyin; Ok, Ercan

2011-01-01

Summary Background and objectives End-stage renal disease is linked to alterations in thyroid hormone levels and/or metabolism, resulting in a high prevalence of subclinical hypothyroidism and low triiodothyronine (T3) levels. These alterations are involved in endothelial damage, cardiac abnormalities, and inflammation, but the exact mechanisms are unclear. In this study, we investigated the relationship between serum free-T3 (fT3) and carotid artery atherosclerosis, arterial stiffness, and vascular calcification in prevalent patients on conventional hemodialysis. Design, setting, participants, & measurements 137 patients were included. Thyroid-hormone levels were determined by chemiluminescent immunoassay, carotid artery–intima media thickness (CA-IMT) by Doppler ultrasonography, carotid-femoral pulse wave velocity (c-f PWV), and augmentation index by Sphygmocor device, and coronary artery calcification (CAC) scores by multi-slice computerized tomography. Results Mean fT3 level was 3.70 ± 1.23 pmol/L. Across decreasing fT3 tertiles, c-f PWV and CA-IMT values were incrementally higher, whereas CACs were not different. In adjusted ordinal logistic regression analysis, fT3 level (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97), age, and interdialytic weight gain were significantly associated with CA-IMT. fT3 level was associated with c-f PWV in nondiabetics but not in diabetics. In nondiabetics (n = 113), c-f PWV was positively associated with age and systolic BP but negatively with fT3 levels (odds ratio = 0.57, 95% confidence interval 0.39 to 0.83). Conclusions fT3 levels are inversely associated with carotid atherosclerosis but not with CAC in hemodialysis patients. Also, fT3 levels are inversely associated with surrogates of arterial stiffness in nondiabetics. PMID:21836150

Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

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Mainous, Arch G; Everett, Charles J; Diaz, Vanessa A; Player, Marty S; Gebregziabher, Mulugeta; Smith, Daniel W

2010-01-01

To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45-84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80-1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

Connective tissue diseases and noninvasive evaluation of atherosclerosis

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Ardita G

2014-06-01

Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

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Sivasubramaniyam, Tharini; Schroer, Stephanie A; Li, Angela; Luk, Cynthia T; Shi, Sally Yu; Besla, Rickvinder; Dodington, David W; Metherel, Adam H; Kitson, Alex P; Brunt, Jara J; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P; Bendeck, Michelle P; Robbins, Clinton S; Woo, Minna

2017-07-20

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

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Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Immune Response to Lipoproteins in Atherosclerosis

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Sonia Samson

2012-01-01

Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

International Nuclear Information System (INIS)

Qiao, Wang; Chaoshu, Tang; Hongfang, Jin; Junbao, Du

2010-01-01

Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H 2 S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H 2 S and inflammatory processes. The role of H 2 S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H 2 S in atherosclerosis.

Calcium intake is not associated with increased coronary artery calcification: the Framingham Study.

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Samelson, Elizabeth J; Booth, Sarah L; Fox, Caroline S; Tucker, Katherine L; Wang, Thomas J; Hoffmann, Udo; Cupples, L Adrienne; O'Donnell, Christopher J; Kiel, Douglas P

2012-12-01

Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors. This was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who attended clinic visits and completed food-frequency questionnaires in 1998-2001 and underwent computed tomography scans 4 y later in 2002-2005. The mean age-adjusted coronary artery-calcification Agatston score decreased with increasing total calcium intake, and the trend was not significant after adjustment for age, BMI, smoking, alcohol consumption, vitamin D-supplement use, energy intake, and, for women, menopause status and estrogen use. Multivariable-adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74) with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use. Our study does not support the hypothesis that high calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk.

A quantitative approach of abdominal aortic atherosclerosis with x-ray computed tomography

International Nuclear Information System (INIS)

Watanabe, Hiromi; Kubota, Kazuo; Ito, Kengo; Ono, Shuichi; Matsuzawa, Taiju

1983-01-01

Currently epidemiologic studies of aortic atherosclerosis are most commonly done by the conventional roentgenological or pathological methods before and after death respectively. Pathological method is difficult and only possible after death. Roentgenological method is simple and useful before death, but its inability to evaluate atherosclerosis in a constant manner is serious drawback. A simple and quantitative method for epidemiological and clinical study of atherosclerosis has been needed. It this study, we examined the usefulness of Calcification Index (C.I.) caliculated from CT films for the evaluation of abdominal aortic atherosclerosis. We analysed 42 patients (32 males, 10 females). They recieved abdominal CT examination and died within a year. First, we got C.I. from their CT films. Then we got Surface Involved (S.I.) of atherosclerotic lesion from their autopsied abdominal aorta with pathological observation. The correlation coefficient between C.I. and S.I. was 0.83 (p<0.001). So we may use C.I. for the evaluation of abdominal aortic atherosclerosis. (author)

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery.

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Kockelkoren, Remko; Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L A W; Verdoorn, Daphne; Mali, Willem P Th M; Hendrikse, Jeroen; Koek, Huiberdina L; de Jong, Pim A; De Vis, Jill B

2017-01-01

Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. First, CT features of the score were circularity (absent, dot(s), medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification.

Myocardial blood flow reserve is impaired in patients with aortic valve calcification and unobstructed epicardial coronary arteries.

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Nel, Karen; Nam, Michael C Y; Anstey, Chris; Boos, Christopher J; Carlton, Edward; Senior, Roxy; Kaski, Juan Carlos; Khattab, Ahmed; Shamley, Delva; Byrne, Christopher D; Stanton, Tony; Greaves, Kim

2017-12-01

Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation. 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay. Mean (±SD) participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6 (22.2) mm, and median coronary calcification score was 43.5AU. Mean MBFR was 2.20 (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression modelling incorporating demographics, coronary plaque characteristics, MBFR, and inflammatory markers, demonstrated that age (β=0.05, 95% CI: 0.02, 0.08, P=0.007), hs-CRP (β=0.09, CI: 0.02, 0.16, P=0.010) and diabetes (β=1.03, CI: 0.08, 1.98, P=0.033), were positively associated with AVCS. MBFR (β=-0.87, CI: -1.44, -0.30, P=0.003), BMI (β=-0.11, CI: -0.21, -0.01, P=0.033), and LDL (β=-0.32, CI: -0.61, -0.03, P=0.029) were negatively associated with AVCS. TPL and coronary calcium score were not independently associated with AVCS when included in the regression model. Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation. Copyright © 2017 Elsevier B.V. All rights

Differential expression of TRAIL and its receptors relative to calcification in AAA

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Liu, Xun; Winrow, Vivienne R.; Horrocks, Michael; Stevens, Cliff R.

2007-01-01

Abdominal aortic aneurysm (AAA) is commonly associated with atherosclerosis. Human AAA tissue displays cells undergoing all stages of apoptosis. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumour cells but not in normal cells. It has death receptors and decoy receptors. An inhibitor of TRAIL, osteoprotegerin (OPG), is involved in osteogenesis and vascular calcification. We investigated TRAIL and its receptors in AAA compared within normal aorta (NA). Both qualitative and quantitative analyses of calcification in AAA walls were determined using Von Kossa staining and pre-operation computer tomography (CT) scans. There was a significant difference in calcification level at different locations in the AAA wall (p < 0.05). Apoptosis was confirmed in AAA by TUNEL assay. A significant difference in TRAIL and its receptor expression was observed between normal aortae and AAA (p < 0.05). Significant differences were also observed between tissues displaying different extents of calcification for TRAIL mRNA (p < 0.05) by RT-PCR examination and OPG protein (p < 0.01) by protein blotting examination. We propose that this pattern of expression of TRAIL and its receptors may contribute to AAA formation and calcification in the AAA wall

Vitamin K status and vascular calcification: evidence from observational and clinical studies.

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Shea, M Kyla; Holden, Rachel M

2012-03-01

Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.

Alcohol and atherosclerosis

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DA LUZ PROTASIO L.

2001-01-01

Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

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Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

2013-01-01

Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

Intraosseous migration of tendinous calcifications: two case reports

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Marinetti, A.; Sessa, M.; Falzone, A.; Della Sala, S.W. [Santa Maria del Carmine Hospital, Department of Radiology, Rovereto, TN (Italy)

2018-01-15

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations. (orig.)

Intraosseous migration of tendinous calcifications: two case reports

International Nuclear Information System (INIS)

Marinetti, A.; Sessa, M.; Falzone, A.; Della Sala, S.W.

2018-01-01

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations. (orig.)

Proliferating macrophages prevail in atherosclerosis.

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Randolph, Gwendalyn J

2013-09-01

Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

A Review of the Effect of Diet on Cardiovascular Calcification

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Rachel Nicoll

2015-04-01

Full Text Available Cardiovascular (CV calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day and phylloquinone (500 μg/day proved protective, as did a serum 25(OHD concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

Calcific periarthritis of the elbow presenting as acute tennis elbow.

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Jawad, F; Jawad, A S M

2014-01-01

A 28-year-old woman presented with sudden acute lateral epicondylitis. There was no history of preceding trauma or repetitive use of the arm. Because of the acute onset and signs of acute inflammation, an X-ray was arranged. The X-ray showed a hyperdense calcified elongated globule distal to the lateral epicondyle. A diagnosis of calcific periarthritis (calcium apatite) of the elbow was made. Calcific periarthritis has rarely been reported as a cause of acute elbow pain.

Prevalence, Impact, and Predictive Value of Detecting Subclinical Coronary and Carotid Atherosclerosis in Asymptomatic Adults

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Baber, Usman; Mehran, Roxana; Sartori, Samantha

2015-01-01

BACKGROUND: Although recent studies suggest that measuring coronary artery calcification (CAC) may be superior to indirect atherosclerotic markers in predicting cardiac risk, there are limited data evaluating imaging-based biomarkers that directly quantify atherosclerosis in different vascular beds...

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery.

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Remko Kockelkoren

Full Text Available Intracranial internal carotid artery (iICA calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification. Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo.First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides. Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort.First, CT features of the score were circularity (absent, dot(s, <90°, 90-270° or 270-360°, thickness (absent, ≥1.5mm, or <1.5mm, and morphology (indistinguishable, irregular/patchy or continuous. A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82 between the categories intimal, medial or absent/indistinguishable.The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological studies on iICA calcification.

An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).

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Liang, C Jason; Budoff, Matthew J; Kaufman, Joel D; Kronmal, Richard A; Brown, Elizabeth R

2012-07-02

Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA

Directory of Open Access Journals (Sweden)

Liang C

2012-07-01

Full Text Available Abstract Background Extent of atherosclerosis measured by amount of coronary artery calcium (CAC in computed tomography (CT has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS. These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA. Methods Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA. The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Results Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26 and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179. Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224. The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. Conclusions The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

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Lisa R. Hoving; Margreet R. de Vries; Rob C. M. de Jong; Saeed Katiraei; Amanda Pronk; Paul H. A. Quax; Vanessa van Harmelen; Ko Willems van Dijk

2018-01-01

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce...

Box-Cox transformation of left-censored data with application to the analysis of coronary artery calcification and pharmacokinetic data.

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Han, Cong; Kronmal, Richard

2004-12-15

Box-Cox transformation is investigated for regression models for left-censored data. Examples are provided using coronary calcification data from the Multi-Ethnic Study of Atherosclerosis and pharmacokinetic data of a nicotine nasal spray. Copyright 2004 John Wiley & Sons, Ltd.

Oral microbiota in patients with atherosclerosis

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Fåk, Frida; Tremaroli, Valentina; Bergström, Göran

2015-01-01

BACKGROUND AND AIMS: Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested...... to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. METHODS: To elucidate whether the oral microbiota composition differed between...... patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. RESULTS...

Neutrophils in atherosclerosis. A brief overview

NARCIS (Netherlands)

Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

2015-01-01

Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

Non-invasive diagnostic methods for atherosclerosis and use in assessing progression and regression in hypercholesterolemia

International Nuclear Information System (INIS)

Tsushima, Motoo; Fujii, Shigeki; Yutani, Chikao; Yamamoto, Akira; Naitoh, Hiroaki.

1990-01-01

We evaluated the wall thickening and stenosis rate (ASI), the calcification rate (ACI), and the wall thickening and calcification stenosis rate (SCI) of the lower abdominal aorta calculated by the 12 sector method from simple or enhanced computed tomography. The intra-observer variation of the calculation of ASI was 5.7% and that of ACI was 2.4%. In 9 patients who underwent an autopsy examination, ACI was significantly correlated with the rate of the calcification dimension to the whole objective area of the abdominal aorta (r=0.856, p<0.01). However, there were no correlations between ASI and the surface involvement or the atherosclerotic index obtained by the point-counting method of the autopsy materials. In the analysis of 40 patients with atherosclerotic vascular diseases, ASI and ACI were also highly correlated with the percentage volume of the arterial wall in relation to the whole volume of the observed artery (r=0.852, p<0.0001) and also the percentage calcification volume (r=0.913, p<0.0001) calculated by the computed method, respectively. The percentage of atherosclerotic vascular diseases increased in the group of both high ASI (over 10%) and high ACI (over 20%). We used SCI as a reliable index when the progression and regression of atherosclerosis was considered. Among patients of hypercholesterolemia consisting of 15 with familial hypercholesterolemia (FH) and 6 non-FH patients, the change of SCI (d-SCI) was significantly correlated with the change of total cholesterol concentration (d-TC) after the treatment (r=0.466, p<0.05) and the change of the right Achilles' tendon thickening (d-ATT) was also correlated with d-TC (r=0.634, p<0.005). However, no correlation between d-SCI and d-ATT was observed. In conclusion, CT indices of atherosclerosis were useful as a noninvasive quantitative diagnostic method and we were able to use them to assess the progression and regression of atherosclerosis. (author)

Function and Therapeutic Potential of Mesenchymal Stem Cells in Atherosclerosis

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Feifei Li

2017-05-01

Full Text Available Atherosclerosis is a complicated disorder and largely attributable to dyslipidaemia and chronic inflammation. Despite therapeutic advances over past decades, atherosclerosis remains the leading cause of mortality worldwide. Due to their capability of immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs have evolved as an attractive therapeutic agent in various diseases including atherosclerosis. Accumulating evidences support the protective role of MSCs in all stages of atherosclerosis. In this review, we highlight the current understanding of MSCs including their characteristics such as molecular markers, tissue distribution, migratory property, immune-modulatory competence, etc. We also summarize MSC functions in animal models of atherosclerosis. MSC transplantation is able to modulate cytokine and chemokine secretion, reduce endothelial dysfunction, promote regulatory T cell function, decrease dyslipidemia, and stabilize vulnerable plaques during atherosclerosis development. In addition, MSCs may migrate to lesions where they develop into functional cells during atherosclerosis formation. Finally, the perspectives of MSCs in clinical atherosclerosis therapy are discussed.

Oral microbiota in patients with atherosclerosis.

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Fåk, Frida; Tremaroli, Valentina; Bergström, Göran; Bäckhed, Fredrik

2015-12-01

Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A review of plant-based compounds and medicinal plants effective on atherosclerosis

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Mehrnoosh Sedighi

2017-01-01

Full Text Available Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice.

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Hoving, Lisa R; de Vries, Margreet R; de Jong, Rob C M; Katiraei, Saeed; Pronk, Amanda; Quax, Paul H A; van Harmelen, Vanessa; Willems van Dijk, Ko

2018-02-03

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden ( E3L ) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

Directory of Open Access Journals (Sweden)

Lisa R. Hoving

2018-02-01

Full Text Available The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L mice. Male E3L mice were fed a high-cholesterol (1% diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype.

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Leon J Schurgers

Full Text Available Vitamin K-antagonists (VKA are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/- model of atherosclerosis.A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD. VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/- mice (10 weeks received a Western type diet (WTD for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1 (VK(1, 1.5 mg/g or vitamin K(1 and warfarin (VK(1&W; 1.5 mg/g & 3.0 mg/g for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/- mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.

Inflammation: a trigger for acute coronary syndrome

International Nuclear Information System (INIS)

SAGER, Hendrik B.; NAHRENDORF, Matthias

2016-01-01

Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis’ most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes.

Acute calcific retropharyngeal tendinitis

International Nuclear Information System (INIS)

Gonzalez, I.; Mendoza, M.; Aperribay, M.; Recondo, J.A.

1998-01-01

Acute calcific tendinitis results from the deposition of calcium hydroxyapatite crystals in peri articular muscular attachments. It usually develops in extremities, most often in shoulders and hips. Although the incidence is much lower, it has been reported to occur in the neck region, where it involves the tendons insertion of the longs colli muscle. We present a case of acute neck pain caused by a calcareous deposition in the tendon of the longs colli muscle, producing inflammation. We describe the clinical and radiologic features (plain radiography, CT,MRI) associated with this entire. (Author) 7 refs

NMR imaging of human atherosclerosis

International Nuclear Information System (INIS)

Toussaint, J.F.

1995-01-01

Diagnosis and prognosis of atherosclerosis can no longer be evaluated with morphological parameters only. A description of atherosclerotic plaque composition is necessary to study the mechanisms of plaque rupture, which depends on collagenous cap and lipid core thicknesses. NMR, as a biochemical imaging technique, allows visualization of these components using T1 contrast (mobile lipids), T2 contrast (cap vs. core), spin density (calcifications), diffusion imaging, 1H and 13C spectroscopy. Today, these imaging sequences allow to study in vitro the effects of interventional techniques such as angioplasty or atherectomy. Clinical investigations begin, which will attempt to develop in vivo microscopy and test the ability of NMR to predict plaque rupture. (author). 13 refs., 7 figs

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

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Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitamin K2 can suppress the expression of Toll-like receptor 2 (TLR2) and TLR4, and inhibit calcification of aortic intima in ApoE-/- mice as well as smooth muscle cells.

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Wang, Zhaojun; Wang, Zhongqun; Zhu, Jie; Long, Xinguang; Yan, Jinchuan

2018-02-01

Background and objectives Vascular calcification is a common complication in atherosclerosis. Accumulating evidence showed that Toll-like receptors (TLRs) mediate pro-inflammatory and atherosclerosis. Recent studies demonstrated that vascular calcification is one of the detrimental effects of vitamin K (Vit K) antagonists. However, the effects of Vit K on the expression of TLR2 and 4 and intimal calcification in artery remained unidentified. Methods and results Eighteen ApoE -/- mice were randomly divided into model group, Vit K-treated group, and control group. The mice of model and Vit K-treated group were fed with high-fat diet, while control group mice were fed with normal diet. Mice of Vit K-treated group were administered orally with vitamin K2 (40 mg.kg -1 .day -1 ) for 12 weeks. Twelve weeks later the aortic sections of mice were acquired and stained with hematoxylin and eosin and von Kossa, respectively. Calcium content and activity of alkaline phosphatase (ALP) at aortic tissues were measured. The expression levels of TLR2 and TLR4 in aorta sections were detected by immunohistochemisty and RT-PCR, respectively. The effects of Vit K on cellular calcification were further studied in A7r5 SMCs. Results demonstrated that high-fat diet induced typical atherosclerosis with intimal calcification in ApoE -/- mice, while in Vit K-treated group atherosclerosis and calcium deposits were not serious; Vit K2 also inhibited cellular calcification in A7r5 SMCs. Quantitative analysis showed that calcium and ALP activity at aortic tissues in the Vit K-treated mice were significantly lower than that of the model group ( P < 0.01); Compared to the control group, the expression levels of TLR2 and TLR4 in the model group were significantly higher ( P < 0.05), while in Vit K-treated group the levels of TLR2 and 4 were significantly lower than that in the model group. Furthermore, the content of calcium was positively related to the expression levels of TLR2 and TLR4

Endothelial GPR124 Exaggerates the Pathogenesis of Atherosclerosis by Activating Inflammation

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Dong-Mei Gong

2018-01-01

Full Text Available Background/Aims: Endothelial cell dysfunction is the principal pathological process underlying atherosclerotic cardiovascular disease. G protein-coupled receptor 124 (GPR124, an orphan receptor in the adhesion GPCR subfamily, promotes angiogenesis in the brain. In the present study, we explored the role of endothelial GPR124 in the development and progression of atherosclerosis in adult mice. Methods: Using tetracycline-inducible transgenic systems, we generated mice expressing GPR124 specifically under control of the Tie-2 promoter. The animal model of atherosclerosis was constructed by intravenously injecting AAV-PCSK9DY into tetracycline-regulated mice and feeding the mice a high-fat diet for 16 consecutive weeks. Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of GPR124 in the pathological process of atherosclerosis. Results: Higher TC (total cholesterol and LDL-C (low density lipoprotein cholesterol levels in serum and greater lipid deposition in the aortic sinus were found in atherosclerotic mice with GPR124 overexpression, coincident with the elevated proliferation of smooth muscle cells. We observed an elevation of ONOO- in the aortic sinus in this model by using immunofluorescence, and the experiments showed that the specific overexpression of GPR124 in the endothelium induced the up-regulation of CD68, NLRP3 and caspase-1 levels in the aortic sinus. Conclusion: The above results indicate that manipulating GPR124 in the endothelium may contribute to delayed pathological progression of atherosclerosis.

Addition of Aspirin to a Fish Oil Rich Diet Decreases Inflammation and Atherosclerosis in ApoE-Null Mice

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Sorokin, Alexander V.; Yang, Zhi-Hong; Vaisman, Boris L.; Thacker, Seth; Yu, Zu-Xi; Sampson, Maureen; Serhan, Charles N.; Remaley, Alan T.

2016-01-01

Aspirin (ASA) is known to alter the production of potent inflammatory lipid mediators, but whether it interacts with omega-3 fatty acids (FA) from fish oil to affect atherosclerosis has not been determined. The goal was to investigate the impact of a fish oil enriched diet alone and in combination with ASA on the production of lipid mediators and atherosclerosis. ApoE−/− female mice were fed for 13 weeks one of the four following diets: Omega-3 FA deficient (OD), Omega-3 FA Rich (OR) (1.8 g Omega-3 FAs/kg • diet per day), Omega-3 FA Rich plus ASA (ORA) (0.1 g ASA/kg • diet per day), or an Omega-3 FA deficient plus ASA (ODA) with supplement levels equivalent to human doses. Plasma lipids, atherosclerosis, markers of inflammation, hepatic gene expression and aortic lipid mediators were determined. Hepatic omega-3 FAs were markedly higher in OR (9.9-fold) and ORA (7-fold) groups. Mice in both OR and ORA groups had 40% less plasma cholesterol in VLDL and LDL fractions, but aortic plaque area formation was only significantly lower in the ORA group (5.5%) compared to the OD group (2.5%). Plasma PCSK9 protein levels were approximately 70% lower in the OR and ORA groups. Pro-inflammatory aortic lipid mediators were 50–70% lower in the ODA group than in the OD group and more than 50% lower in the ORA group. In summary, less aortic plaque lesions and aortic pro-inflammatory lipid mediators were observed in mice on the fish oil diet plus ASA versus just the fish oil diet. PMID:27394692

The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients.

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Lo, Janet; Plutzky, Jorge

2012-06-01

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

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Santilli, S; Kast, D R; Grozdev, I; Cao, L; Feig, R L; Golden, J B; Debanne, S M; Gilkeson, R C; Orringer, C E; McCormick, T S; Ward, N L; Cooper, K D; Korman, N J

2016-07-22

Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. A tertiary care cohort of psoriasis patients have a high prevalence of early

[¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

DEFF Research Database (Denmark)

Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

2015-01-01

[(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...

Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

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While animal studies found vitamin K treatment reduced vascular calcification, human data are limited. Using a case-cohort design, we determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-ethnic Study of Atherosclerosis. Serum phylloquinone (v...

Lower Extremity Arterial Calcification as a Predictor of Coronary Atherosclerosis in Patients with Peripheral Arterial Disease

International Nuclear Information System (INIS)

Shin, Hwa Seon; Jung Park, Mi; Nyeo Jeon, Kyung; Min Cho, Jae; Soo Bae, Kyung; Seob Choi, Dae; Boem Na, Jae; Cheol Choi, Ho; Young Choi, Hye; Eun Kim, Ji; Bueum Cho, Soo; Eun Park, Sung

2016-01-01

Until now, there has been no study on the relationship between the calcification of the lower extremity arteries and significant coronary arterial disease (CAD). To evaluate whether lower extremity calcium scores (LECS) are associated with CAD and whether this can predict multivessel-CAD in patients with peripheral arterial disease (PAD). We retrospectively enrolled 103 PAD patients without cardiac symptoms or known CAD. All patients underwent cardiac computed tomography (CT) and lower extremity CT within 1 month and were categorized as nonsignificant CAD, single-CAD, or multivessel-CAD. The coronary calcium scores (CCS) were quantitatively measured according to the Agatston method and LECS were semi-quantitatively measured according to the presence of lower extremity calcification in the segment. The extent of CAD was evaluated according to the presence of ≥ 50% luminal diameter stenosis in the segment of CAD. LECS in multivessel-CAD were significantly higher than those in nonsignificant CAD (10.0 ± 5.8 versus 4.0 ± 3.1, P < 0.001). LECS significantly correlated with CCS (r = 0.831, P < 0.001) and the extent of CAD (r = 0.631, P < 0.001). Multivariate regression analysis demonstrated LECS and log-transformed CCS were independent predictors for multivessel-CAD. In receiver operating characteristic curve analysis, the diagnostic performance of LECS was 0.807 (95% confidence interval = 0.724-0.891, P < 0.001) for predicting multivessel-CAD. Peripheral arterial calcification is significantly correlated with CAD extent in patients with PAD. Peripheral arterial calcification can be a useful marker for predicting multivessel-CAD

Are air pollution and traffic noise independently associated with atherosclerosis: the Heinz Nixdorf Recall Study.

Science.gov (United States)

Kälsch, Hagen; Hennig, Frauke; Moebus, Susanne; Möhlenkamp, Stefan; Dragano, Nico; Jakobs, Hermann; Memmesheimer, Michael; Erbel, Raimund; Jöckel, Karl-Heinz; Hoffmann, Barbara

2014-04-01

Living close to high traffic has been linked to subclinical atherosclerosis, however it is not clear, whether fine particulate matter (PM) air pollution or noise, two important traffic-related exposures, are responsible for the association. We investigate the independent associations of long-term exposure to fine PM and road traffic noise with thoracic aortic calcification (TAC), a reliable measure of subclinical atherosclerosis. We used baseline data (2000-2003) from the German Heinz Nixdorf Recall Study, a population-based cohort of 4814 randomly selected participants. We assessed residential long-term exposure to PM with a chemistry transport model, and to road traffic noise using façade levels from noise models as weighted 24 h mean noise (Lden) and night-time noise (Lnight). Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. We used multiple linear regression to estimate associations of environmental exposures with ln(TAC+1), adjusting for each other, individual, and neighbourhood characteristics. In 4238 participants (mean age 60 years, 49.9% male), PM2.5 (aerodynamic diameter ≤2.5 µm) and Lnight are both associated with an increasing TAC-burden of 18.1% (95% CI: 6.6; 30.9%) per 2.4 µg/m(3) PM2.5 and 3.9% (95% CI 0.0; 8.0%) per 5dB(A) Lnight, respectively, in the full model and after mutual adjustment. We did not observe effect measure modification of the PM2.5 association by Lnight or vice versa. Long-term exposure to fine PM and night-time traffic noise are both independently associated with subclinical atherosclerosis and may both contribute to the association of traffic proximity with atherosclerosis.

A CT study of the prevalence of carotid artery calcification in dental patients

International Nuclear Information System (INIS)

Yoon, Suk Ja; Lee, Jae Seo; Yoon, Woong

2006-01-01

Stroke is one of the leading causes of death in Korea. Atherosclerotic disease in the carotid artery bifurcation is the most common cause of stroke. The carotid artery calcification is easily appreciated by CT(Computed tomography). CT is often taken in a dental hospital for the diagnosis of inflammation. injury, cyst or tumor on maxillofacial region. However, there was no report of carotid artery calcification on CT in dental patients. The presence of carotid artery calcification was evaluated by an experienced radiologist on CT scans of 287 patients (166 males, 121 females, average age 42, range 6 to 86 years) and the medical history of the patient and the interpretation of CT were reviewed. Carotid artery calcification was detected on CT scans of 57 patients (19.8%; 35 males, 22 females). All the male patients with carotid artery calcification were older than 50, and all the female patients with carotid artery calcification were older than 60. Among the 57 patients, 10 had Diabetes mellitus, 20 had cardiovascular disease, 3 had history of stroke and 3 underwent radiation therapy for head and neck cancer. Carotid artery calcification was not included in the interpretation of CT of dental patients except one patient. The prevalence of carotid artery calcification on CT of dental patients was about 20% in this study. Carotid artery calcification should be included in the interpretation of CT of dental patients

Recent advances in pathogenesis, assessment, and treatment of atherosclerosis [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

J. David Spence

2016-07-01

Full Text Available In recent years, there have been a number of advances in the pathogenesis and treatment of atherosclerosis and in assessing prognosis in carotid atherosclerosis. Risk stratification to improve vascular prevention by identifying patients most likely to benefit from intensive therapy is much improved by measuring carotid plaque burden. In patients with asymptomatic carotid stenosis, a number of modalities can be used to identify the 10-15% who could benefit from endarterectomy or stenting. Transcranial Doppler embolus detection, echolucency and ulceration on 3D ultrasound, intraplaque hemorrhage on magnetic resonance imaging (MRI, and reduced cerebrovascular reserve are useful already; new approaches including plaque texture on ultrasound and imaging of plaque inflammation and early calcification on positron emission tomography/computed tomography (PET/CT are in development. The discovery that the intestinal microbiome produces vasculotoxic metabolites from dietary constituents such as carnitine in meat (particularly red meat and phosphatidylcholine from egg yolk and other sources has revolutionized nutritional aspects of vascular prevention. Because many of these vasculotoxic metabolites are removed by the kidney, it is particularly important in patients with renal failure to limit their intake of red meat and egg yolk. A new approach to lowering low-density lipoprotein (LDL cholesterol by blocking the action of an enzyme that destroys LDL receptors promises to revolutionize vascular prevention once less costly treatments are developed, and a new approach to vascular prevention—“treating arteries instead of risk factors”—shows promise but requires randomized trials. These advances all promise to help in the quest to prevent strokes in high-risk patients.

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

Science.gov (United States)

Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2014-01-01

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

Science.gov (United States)

Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

2013-05-24

Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

Science.gov (United States)

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

Pericardial and thoracic peri-aortic adipose tissues contribute to systemic inflammation and calcified coronary atherosclerosis independent of body fat composition, anthropometric measures and traditional cardiovascular risks

International Nuclear Information System (INIS)

Yun, Chun-Ho; Lin, Tin-Yu; Wu, Yih-Jer; Liu, Chuan-Chuan; Kuo, Jen-Yuan; Yeh, Hung-I.; Yang, Fei-Shih; Chen, Su-Chiu; Hou, Charles Jia-Yin; Bezerra, Hiram G.; Hung, Chung-Lieh; Cury, Ricardo C.

2012-01-01

Background: Coronary atherosclerosis has traditionally been proposed to be associated with several cardiovascular risk factors and anthropometric measures. However, clinical data regarding the independent value of visceral adipose tissue in addition to such traditional predictors remains obscure. Materials and methods: We subsequently studied 719 subjects (age: 48.1 ± 8.3 years, 25% females) who underwent multidetector computed tomography (MDCT) for coronary calcium score (CCS) quantification. Baseline demographic data and anthropometric measures were taken with simultaneous body fat composition estimated. Visceral adipose tissue of pericardial and thoracic peri-aortic fat was quantified by MDCT using TeraRecon Aquarius workstation (San Mateo, CA). Traditional cardiovascular risk stratification was calculated by metabolic (NCEP ATP III) and Framingham (FRS) scores and high-sensitivity CRP (Hs-CRP) was taken to represent systemic inflammation. The independent value of visceral adipose tissue to systemic inflammation and CCS was assessed by utilizing multivariable regression analysis. Results: Of all subjects enrolled in this study, the mean values for pericardial and peri-aortic adipose tissue were 74.23 ± 27.51 and 7.23 ± 3.69 ml, respectively. Higher visceral fat quartile groups were associated with graded increase of risks for cardiovascular diseases. Both adipose burdens strongly correlated with anthropometric measures including waist circumference, body weight and body mass index (all p < 0.001). In addition, both visceral amount correlates well with ATP and FRS scores, all lipid profiles and systemic inflammation marker in terms of Hs-CRP (all p < 0.001). After adjustment for baseline variables, both visceral fat were independently related to Hs-CRP levels (all p < 0.05), but only pericardial fat exerted independent role in coronary calcium deposit. Conclusion: Both visceral adipose tissues strongly correlated with systemic inflammation beyond traditional

C-reactive protein in relation to early atherosclerosis and periodontitis.

Science.gov (United States)

Yakob, Maha; Meurman, Jukka H; Jogestrand, Tomas; Nowak, Jacek; Söder, Per-Östen; Söder, Birgitta

2012-02-01

Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

Incidence of Deflux® calcification masquerading as distal ureteric calculi on ultrasound.

Science.gov (United States)

Yankovic, Francisca; Swartz, Robert; Cuckow, Peter; Hiorns, Melanie; Marks, Stephen D; Cherian, Abraham; Mushtaq, Imran; Duffy, Patrick; Smeulders, Naima

2013-12-01

Dextranomer-hyaluronic acid (Deflux(®)), the most widely used compound in the endoscopic treatment of vesico-ureteric reflux (VUR) today, is believed to provoke only minimal inflammation. Reports of calcification of Deflux(®) are increasing. We ascertain the incidence of Deflux(®) calcification appearing as distal ureteric calculi on ultrasound. Three cases (2 external patients) of ureteroscopy for calcified submucosal Deflux(®) prompted a retrospective review of the notes and imaging of all children treated with Deflux(®) for VUR between December 2000 and January 2011 at Great Ormond Street Hospital. 232 children (M:F = 5:3) received Deflux(®) for VUR at median age 2 years (range 2 months-12 years). Follow-up annual ultrasound, performed in all, identified calcification in 2. The interval between Deflux(®) injection and presentation of its calcification was 4 years. 104 of the 232 children had been followed up for 4-10 years. Considering the observed lag-period, after 4 years the incidence of calcification of Deflux(®) on ultrasound was 2% (2/104). Patients should be warned that calcification of Deflux(®) can occur. Misinterpretation as ureteric stones is common and may lead to unnecessary ureteroscopy. In this series, the incidence of calcification of Deflux(®) on ultrasound after 4 years was 2%. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Inflammatory markers and extent and progression of early atherosclerosis

DEFF Research Database (Denmark)

Willeit, Peter; Thompson, Simon G; Agewall, Stefan

2016-01-01

BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT)...

Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings

OpenAIRE

Madan, Monika; Amar, Salomon

2008-01-01

Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed eit...

Influence of Erythrocyte Membrane Stability in Atherosclerosis.

Science.gov (United States)

da Silva Garrote-Filho, Mario; Bernardino-Neto, Morun; Penha-Silva, Nilson

2017-04-01

The purpose of this study is to show how an excess of cholesterol in the erythrocyte membrane contributes stochastically to the progression of atherosclerosis, leading to damage in blood rheology and O 2 transport, deposition of cholesterol (from trapped erythrocytes) in an area of intraplaque hemorrhage, and local exacerbation of oxidative stress. Cholesterol contained in the membrane of erythrocytes trapped in an intraplaque hemorrhage contributes to the growth of the necrotic nucleus. There is even a relationship between the amount of cholesterol in the erythrocyte membrane and the severity of atherosclerosis. In addition, the volume variability among erythrocytes, measured by RDW, is predictive of a worsening of this disease. Erythrocytes contribute to the development of atherosclerosis in several ways, especially when trapped in intraplate hemorrhage. These erythrocytes are oxidized and phagocytosed by macrophages. The cholesterol present in the membrane of these erythrocytes subsequently contributes to the growth of the atheroma plaque. In addition, when they rupture, erythrocytes release hemoglobin, which leads to the generation of free radicals. Finally, increased RDW may predict the worsening of atherosclerosis, due to the effects of inflammation and oxidative stress on erythropoiesis and erythrocyte volume. A better understanding of erythrocyte participation in atherosclerosis may contribute to the improvement of the prevention and treatment strategies of this disease.

Oxyradical Stress, Endocannabinoids, and Atherosclerosis

Directory of Open Access Journals (Sweden)

Anberitha T. Matthews

2015-12-01

Full Text Available Atherosclerosis is responsible for most cardiovascular disease (CVD and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG. Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.

Medial arterial calcification, calcific aortic stenosis and mitral annular calcification in a diabetic patient with severe autonomic neuropathy.

LENUS (Irish Health Repository)

Cronin, C C

2012-02-03

Medial arterial calcification (Monckeberg\\'s arteriosclerosis) is well described in diabetic patients with autonomic neuropathy. There is also a high prevalence of diabetes mellitus among subjects with calcific aortic stenosis and mitral annular calcification. We describe a diabetic patient with autonomic neuropathy and extensive medial arterial calcification who also had calcification of the aortic valve and of the mitral valve annulus. We propose that autonomic neuropathy may play a role in calcification of these structures at the base of the heart.

Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges.

Science.gov (United States)

Arenillas, Juan F; Alvarez-Sabín, José

2005-01-01

Intracranial large-artery atherosclerosis is a major cause of ischemic stroke worldwide. Patients affected by this disease are at a high risk of suffering recurrent ischemic events despite antithrombotic therapy. Progression and a greater extent of intracranial atherosclerosis imply a higher risk for recurrence. Studies performed by our group in patients with symptomatic intracranial large-artery atherosclerosis have shown that: (1) C-reactive protein predicts its progression and recurrence, suggesting that inflammation may play a deleterious role in this condition; (2) a high level of the anti-angiogenic endostatin is also associated with a progressive and recurrent intracranial atherosclerosis, which might support a beneficial role for angiogenesis in this group of patients; and (3) elevated lipoprotein(a) concentration and diabetes mellitus characterize those patients with a higher number of intracranial stenoses. 2005 S. Karger AG, Basel

Probiotics and atherosclerosis – a new challenge?

Directory of Open Access Journals (Sweden)

Chan Yee Kwan

2012-06-01

Full Text Available Background Atherosclerosis is the major cause of cardiovascular disease and stroke, which are among the top 10 leading causes of death worldwide. Pathogen-associated molecular patterns (PAMPs can activate toll-like receptors (TLRs and activate nuclear factor kappa B (NFκB signaling, a central pathway in inflammation, which regulates genes that encode proinflammatory molecules essential in atherogenesis. Lipopolysaccharides (LPS, which is unique to gram negative bacteria, as well as peptidoglycan (PGN, which is found in gram positive bacteria are PAMPS and ligands of TLR4 and TLR2, respectively, both of which are essential in plaque progression in atherosclerosis. Gastrointestinal tract is suggested to be the major site for absorption and translocation of TLR2 and TLR4 stimulants. Inflammation can result in a ‘leaky gut’ that leads to higher bacterial translocation, eventually the accumulation of LPS and PGN would activate TLRs and trigger inflammation through NFκB and promote further systemic complication like atherosclerosis. Probiotics, can protect the intestinal barrier to reduce bacterial translocation and have potential systemic anti-inflammatory properties.To evaluate whether probiotics can help reduce atherosclerotic development using in vivo study.Apolipoprotein E knockout (ApoE−/ −  mice were fed on high fat diet alone, with telmisartan (Tel (1 or 5 mg/kg/day, positive controls or with probiotics (VSL#3/LGG with or without Tel (1 mg/kg/day for 12 weeks.Probiotics, Tel, or a combination of both reduced lesion size at the aortic root significantly; VSL#3 reduced serum inflammatory adhesion molecules soluble E- (sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1, soluble vascular cell adhesion molecule 1 (sVCAM-1, and plaque disrupting factor matrix metalloproteinase (MMP-9 significantly; probiotics and Tel at 5 mg/kg/day could induce changes in gut microbiota population; the efficiency of lesion reduction seemed

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

International Nuclear Information System (INIS)

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-01-01

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

Energy Technology Data Exchange (ETDEWEB)

Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

2013-05-10

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

Usefulness of detecting atherosclerosis by computed tomography. A relation to coronary artery stenosis

International Nuclear Information System (INIS)

Takasu, Junichiro; Yamamoto, Rie; Yokoyama, Kenichi

1999-01-01

Reports evaluating coronary artery calcification detection by nonenhanced computed tomography (CT) have verified the usefulness for diagnosis of coronary artery disease. In the condition of a mobile CT scanning at a public health examination, however, determination of coronary calcification remains unclear. We investigated, under this scanning condition, a relation between the characteristic of coronary artery calcification determined by conventional CT and coronary disease on arteriogram. The quantification of aortic wall thickening by enhanced CT was examined on the usefulness of detecting coronary artery disease. The CT density score and the characteristics of aortic atherosclerosis for 159 male patients 30 year-old or more (average age 60.7 years) were examined the relation to coronary artery stenoses. The CT density score was the strongest independent variable for determining the existence of coronary disease. The CT density cutoff score for detection of coronary disease was 50 equal to 50 HU the maximal CT density in the coronary arteries. The maximal aortic wall thickness was the strongest significant variable independent of the noted coronary risk factors for the severity of coronary stenosis on arteriogram. (author)

MITRAL ANNULAR CALCIFICATION IN ELDERLY PATIENTS: RELATIONSHIP WITH CLINICAL MANIFESTATIONS AND RISK FACTORS OF CARDIOVASCULAR DISEASES CAUSED BY ATHEROSCLEROSIS

Directory of Open Access Journals (Sweden)

G. M. Urvacheva

2011-01-01

Full Text Available The aim – to study the association of the mitral annular calcification (MAC with traditional risk factors and clinical manifestations of atherosclerosisin patients aged over 65 years without diabetes.Materials and methods. The prospective study included 100 patients over 65 years with MAC consistently identified among 910 ambulatory patients after transthoracic Doppler echocardiography in relation to the symptoms of cardiovascular disease. The comparison group consisted of 65 consecutively examined patients aged over 65 with no MAC.Results. When comparing risk factors in patients with and without MAC, MAC statistically significant differences was found with age (72,4 ± 5,4 and 70,2 ± 4,3 years, respectively; p = 0,006, the incidence of hypertension of moderate and severe degree (99 % and 90.8 % of patients, p = 0.012, levels of total cholesterol – TC (6,91 ± 0,92 and 6,2 ± 0,90 mmol / l, p = 0.0008 and lipoproteinlow density (3,57 ± 0,95 and 2,96 ± 0,96 mmol / l, p = 0.004 in subgroups of patients aged 65 to 70 years. In multivariate analysis remained statistically significant association of MAC only with age (p = 0,025, β = 0,173 and total cholesterol levels (p = 0,040; β = 0,160. Averages of the coefficient of atherogenicity of blood lipids, systolic and diastolic blood pressure, C-reactive protein, body mass index, waist circumference, the frequency of smoking, and risk assessment on a scale of SCORE in groups of patients with and without MAC did not differ significantly. In patients with MAC was higher incidence of myocardial infarction (p = 0.024 and more often than in patients without MAC, diagnosed coronary heart disease (p = 0.029. In the multivariate analysis adjusted for age and total cholesterol level is set significantly associated with the presence and extent of MAC with symptomatic atherosclerotic peripheral arterial disease (p < 0,00001; β = 0,410.Conclusion. In patients with MAC older than 65 years without diabetes

Metabonomics-based omics study and atherosclerosis

OpenAIRE

Wu, Duo-jiao; Zhu, Bi-jun; Wang, Xiang-dong

2011-01-01

Atherosclerosis results from dyslipidemia and systemic inflammation, associated with the strong metabolism and interaction between diet and disease. Strategies based on the global profiling of metabolism would be important to define the mechanisms involved in pathological alterations. Metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. Metabonomics has been used in combination w...

An essential role for diet in exercise-mediated protection against dyslipidemia, inflammation and atherosclerosis in ApoE⁻/⁻ mice.

Directory of Open Access Journals (Sweden)

Liliana Cesar

2011-02-01

Full Text Available Diet and exercise promote cardiovascular health but their relative contributions to atherosclerosis are not fully known. The transition from a sedentary to active lifestyle requires increased caloric intake to achieve energy balance. Using atherosclerosis-prone ApoE-null mice we sought to determine whether the benefits of exercise for arterial disease are dependent on the food source of the additional calories.Mice were fed a high-fat diet (HF for 4.5 months to initiate atherosclerosis after which time half were continued on HF while the other half were switched to a high protein/fish oil diet (HP. Half of each group underwent voluntary running. Food intake, running distance, body weight, lipids, inflammation markers, and atherosclerotic plaque were quantified. Two-way ANOVA tests were used to assess differences and interactions between groups. Exercised mice ran approximately 6-km per day with no difference between groups. Both groups increased food intake during exercise and there was a significant main effect of exercise F((1,44 = 9.86, p<0.01 without interaction. Diet or exercise produced significant independent effects on body weight (diet: F(1,52 = 6.85, p = 0.012; exercise: F(1,52 = 9.52, p<0.01 with no significant interaction. The combination of HP diet and exercise produced a greater decrease in total cholesterol (F(1, 46 = 7.9, p<0.01 and LDL (F(1, 46 = 7.33, p<0.01 with a large effect on the size of the interaction. HP diet and exercise independently reduced TGL and VLDL (p<0.05 and 0.001 respectively. Interleukin 6 and C-reactive protein were highest in the HF-sedentary group and were significantly reduced by exercise only in this group. Plaque accumulation in the aortic arch, a marker of cardiovascular events was reduced by the HP diet and the effect was significantly potentiated by exercise only in this group resulting in significant plaque regression (F1, 49 = 4.77, p<0.05.In this model exercise is

Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFNγ+ Th1/Tregs.

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Butcher, Matthew J; Filipowicz, Adam R; Waseem, Tayab C; McGary, Christopher M; Crow, Kevin J; Magilnick, Nathaniel; Boldin, Mark; Lundberg, Patric S; Galkina, Elena V

2016-11-11

Forkhead box P3 + T regulatory cells (Tregs) are key players in maintaining immune homeostasis. Evidence suggests that Tregs respond to environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-driven inflammation affects Treg homeostasis, but the mechanisms governing this phenomenon are unclear. Here, we address whether atherosclerosis impacts Treg plasticity and functionality in Apoe - /- mice, and what effect Treg plasticity might have on the pathology of atherosclerosis. We demonstrate that atherosclerosis promotes Treg plasticity, resulting in the reduction of CXCR3 + Tregs and the accumulation of an intermediate Th1-like interferon (IFN)-γ + CCR5 + Treg subset (Th1/Tregs) within the aorta. Importantly, Th1/Tregs arise in atherosclerosis from bona fide Tregs, rather than from T-effector cells. We show that Th1/Tregs recovered from atherosclerotic mice are dysfunctional in suppression assays. Using an adoptive transfer system and plasticity-prone Mir146a -/- Tregs, we demonstrate that elevated IFNγ + Mir146a -/- Th1/Tregs are unable to adequately reduce atherosclerosis, arterial Th1, or macrophage content within Apoe -/- mice, in comparison to Mir146a +/+ Tregs. Finally, via single-cell RNA-sequencing and real-time -polymerase chain reaction, we show that Th1/Tregs possess a unique transcriptional phenotype characterized by coexpression of Treg and Th1 lineage genes and a downregulation of Treg-related genes, including Ikzf2, Ikzf4, Tigit, Lilrb4, and Il10. In addition, an ingenuity pathway analysis further implicates IFNγ, IFNα, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), T-cell receptor, and Csnk2b-related pathways in regulating Treg plasticity. Atherosclerosis drives Treg plasticity, resulting in the accumulation of dysfunctional IFNγ + Th1/Tregs that may permit further arterial inflammation and atherogenesis. © 2016 American Heart Association, Inc.

Association between asymptomatic inflammatory prostatitis NIH category IV and prostatic calcification in patients with obstructive benign prostatic hyperplasia.

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Engelhardt, Paul F; Seklehner, Stephan; Brustmann, Herman; Riedl, Claus R; Lusuardi, Lukas

2016-06-01

The aim of this study was to evaluate the incidence of prostatic calcification and prostatitis NIH category IV in patients with obstructive BPH. Ninety-six patients with obstructive BPH who had undergone transurethral electroresection of the prostate gland were evaluated. In accordance with a preoperative transrectal ultrasound examination, patients were divided into one group with prostatic calcification (N.=31) and one without (N.=65). Prostatitis NIH category IV was classified according to the grading system by Irani. Correlations between the incidence of prostatic calcification, histological prostatitis, PSA, uric acid, cholesterol, triglycerides, CRP, IPSS, IIEF-25, and NIC-CPSI were analyzed. A stone analysis of prostatic calcification was performed using X-ray powder diffraction. Sixty-nine (71.9%) patients had NIH category IV prostatitis, accounting for 83.9% of those with prostatic calcification versus 66.1% of those without (Pprostatic calcification and the severity of inflammation (Pprostatic calcifications were elevated levels of uric acid. Such patients were 1.4times more likely of having calcifications in the prostate gland (OR=1.4, Pprostatic calcification. These were significantly more common in patients with NIH category IV prostatitis.

Suppression of atherosclerosis by synthetic REV-ERB agonist

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Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

Proinflammatory Status, Genetics and Atherosclerosis

Czech Academy of Sciences Publication Activity Database

Poledne, R.; Lorenzová, A.; Stávek, P.; Valenta, Zdeněk; Hubáček, J.; Suchánek, R.; Piťha, J.

2009-01-01

Roč. 58, Suppl. 2 (2009), S111-S118 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M06014 Grant - others:GA MŠk(CZ) 1M0510 Program:1M Institutional research plan: CEZ:AV0Z10300504 Keywords : atherosclerosis * inflammation * C-reactive protein * genetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.430, year: 2009 http://www.biomed.cas.cz/physiolres/pdf/58%20Suppl%202/58_S111.pdf

Neighborhood characteristics influence DNA methylation of genes involved in stress response and inflammation: The Multi-Ethnic Study of Atherosclerosis.

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Smith, Jennifer A; Zhao, Wei; Wang, Xu; Ratliff, Scott M; Mukherjee, Bhramar; Kardia, Sharon L R; Liu, Yongmei; Roux, Ava V Diez; Needham, Belinda L

2017-08-01

Living in a disadvantaged neighborhood is associated with poor health outcomes even after accounting for individual-level socioeconomic factors. The chronic stress of unfavorable neighborhood conditions may lead to dysregulation of the stress reactivity and inflammatory pathways, potentially mediated through epigenetic mechanisms such as DNA methylation. We used multi-level models to examine the relationship between 2 neighborhood conditions and methylation levels of 18 genes related to stress reactivity and inflammation in purified monocytes from 1,226 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of US adults. Neighborhood socioeconomic disadvantage, a summary of 16 census-based metrics, was associated with DNA methylation [False discovery rate (FDR) q-value ≤ 0.1] in 2 out of 7 stress-related genes evaluated (CRF, SLC6A4) and 2 out of 11 inflammation-related genes (F8, TLR1). Neighborhood social environment, a summary measure of aesthetic quality, safety, and social cohesion, was associated with methylation in 4 of the 7 stress-related genes (AVP, BDNF, FKBP5, SLC6A4) and 7 of the 11 inflammation-related genes (CCL1, CD1D, F8, KLRG1, NLRP12, SLAMF7, TLR1). High socioeconomic disadvantage and worse social environment were primarily associated with increased methylation. In 5 genes with significant associations between neighborhood and methylation (FKBP5, CD1D, F8, KLRG1, NLRP12), methylation was associated with gene expression of at least one transcript. These results demonstrate that multiple dimensions of neighborhood context may influence methylation levels and subsequent gene expression of stress- and inflammation-related genes, even after accounting for individual socioeconomic factors. Further elucidating the molecular mechanisms underlying these relationships will be important for understanding the etiology of health disparities.

The Relationship of Body Composition and Coronary Artery Calcification in Apparently Healthy Korean Adults

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Jung-Hee Yu

2013-03-01

Full Text Available BackgroundWe investigated the association of coronary artery calcium score (CACS with body composition and insulin resistance in apparently healthy Korean adults.MethodsNine hundred forty-five participants (mean age, 48.9 years; 628 men in a medical check-up program were selected for analysis. Body composition was assessed by bioelectrical impedance analysis (BIA. Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR. The CACS was assessed by multidetector computed tomography.ResultsOne hundred forty-six subjects (15.4% showed coronary artery calcification and 148 subjects (15.7% had metabolic syndrome. CACS showed a significant positive correlation with age, fasting glucose level, waist circumference (WC, blood pressure, hemoglobin A1c, HOMA-IR, and waist-hip ratio (WHR assessed by BIA. CACS had a negative correlation with high density lipoprotein cholesterol (HDL-C. Subjects with high CACS showed significantly higher mean WHRs and lower mean values for lean body mass compared with subjects without coronary artery calcification. In logistic regression analyses with coronary artery calcification as the dependent variable, the highest quartile of WHR showed a 3.125-fold increased odds ratio for coronary artery calcification compared with the lowest quartile after adjustment for confounding variables. When receiver operating characteristics analyses were performed with coronary artery calcification as the result variable, WHR showed the largest area under the curve (AUC value among other variables except for age and WC in women (AUC=0.696 for WHR, 0.790 for age, and 0.719 for WC in women.ConclusionIn our study population of apparently healthy Korean adults, WHR was the most significant predictor for coronary artery calcification among other confounding factors, suggesting that it may have implication as a marker for early atherosclerosis.

Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis.

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Poyrazoglu, Hatice Gamze; Vurdem, Umit Erkan; Arslan, Alev; Uytun, Salih

2016-10-01

Migraine is a commonly seen neurovascular disorder during childhood. Inflammation induced by the activation of cytokines and neuropeptides is implied in its pathophysiology. There is an association between inflammation and atherosclerosis in patients with migraine. In addition, there is a strong correlation between early atherosclerotic wall lesions and carotid intima-media thickness (CIMT). The study population consisted of 57 migraine patients aged 5-17 years, as well as 47 healthy children who served as the control group. Those migraine patients who were not receiving any medications at the interictal period were compared to healthy controls in terms of their measured lipid levels, thyroid function, vitamin B12 levels, serum iron levels, iron binding capacity, complete blood count, C-reactive protein (CRP) levels, and carotid intima-media thickness (CIMT) scores, which may comprise risk factors for atherosclerosis. When children in the migraine and control groups were compared in terms of those risk factors that are known to be related to vascular changes, no significant differences were found. However, a significant difference was detected in CIMT values (P < 0.05). Atherosclerosis commences in childhood, and there is a long period of time before the onset of ischemic symptoms occurs. In children with migraine, an evaluation of CIMT can be used as a non-invasive imaging modality to detect atherosclerosis, which develops in the context of chronic inflammation. In this way, measures to reduce morbidity and mortality, which may result from cardiovascular diseases, can be implemented.

Applying nanomedicine in maladaptive inflammation and angiogenesis

NARCIS (Netherlands)

Alaarg, Amr; Pérez-Medina, Carlos; Metselaar, Josbert M.; Nahrendorf, Matthias; Fayad, Zahi A.; Storm, Gert; Mulder, Willem J. M.

2017-01-01

Inflammation and angiogenesis drive the development and progression of multiple devastating diseases such as atherosclerosis, cancer, rheumatoid arthritis, and inflammatory bowel disease. Though these diseases have very different phenotypic consequences, they possess several common

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

Science.gov (United States)

Thompson, Randall C; Allam, Adel H; Lombardi, Guido P; Wann, L Samuel; Sutherland, M Linda; Sutherland, James D; Soliman, Muhammad Al-Tohamy; Frohlich, Bruno; Mininberg, David T; Monge, Janet M; Vallodolid, Clide M; Cox, Samantha L; Abd el-Maksoud, Gomaa; Badr, Ibrahim; Miyamoto, Michael I; el-Halim Nur el-Din, Abd; Narula, Jagat; Finch, Caleb E; Thomas, Gregory S

2013-04-06

Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; phuman beings raises the possibility of a more basic predisposition to the disease. National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis

DEFF Research Database (Denmark)

Sorensen, Grith L; Bladbjerg, Else Marie; Steffensen, Rudi

2016-01-01

OBJECTIVE: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (p......SP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis. METHODS: We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima......: The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely...

Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice

DEFF Research Database (Denmark)

Koenen, Rory R; von Hundelshausen, Philipp; Nesmelova, Irina V

2009-01-01

Atherosclerosis is characterized by chronic inflammation of the arterial wall due to chemokine-driven mononuclear cell recruitment. Activated platelets can synergize with chemokines to exacerbate atherogenesis; for example, by deposition of the chemokines platelet factor-4 (PF4, also known as CXC...

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

International Nuclear Information System (INIS)

Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

2015-01-01

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [ 125 I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [ 125 I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h

Tofacitinib ameliorates atherosclerosis and reduces foam cell formation in apoE deficient mice.

Science.gov (United States)

Wang, Zaicun; Wang, Shumei; Wang, Zunzhe; Yun, Tiantian; Wang, Chenchen; Wang, Huating

2017-08-19

Atherosclerosis is a chronic inflammatory cardiovascular disease with high mortality worldwide. Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. However, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of Tofacitinib on atherogenic diet (ATD)-induced atherosclerosis using apolipoprotein E deficient (apoE-/-) mice. Atherosclerosis-prone apoE-/- mice were fed with ATD and treated with or without Tofacitinib through intragastrical administration (10 mg kg -1 day -1 ) for 8 weeks. Our results showed that Tofacitinib did not change plasma lipids, while significantly reduced the levels of plasma pro-inflammatory cytokines IL-6 and TNF-α. It also significantly attenuated atherosclerotic plaque lesion in the aortic root and macrophages contained in plaque as shown with Mac2 immuno-staining. Peritoneal macrophages (PMC) were separated from apoE-/- mice fed with 8-week ATD, and then subjected to inflammation tests. Flow cytometry analysis of F4/80 and CD206 and mRNA levels of M1 and M2 macrophages markers showed that M1 macrophages decreased while M2 macrophages increased in Tofacitinib treated group. Expressions of other inflammatory genes also indicated an anti-inflammatory status in mice treated with Tofacitinib. Ox-LDL was used to induce foam cell formation from PMC in wild type mice, and the results displayed a reduced formation of foam cells and decreased inflammation in mice with Tofacitinib administration (1 μM). The mRNA and protein levels of ATP binding cassette subfamily A member 1 (ABCA1), a key gene involved in cholesterol efflux, remarkably increased, while it was absence of alterations in scavenger receptors expression. Therefore, we demonstrated that Tofacitinib could attenuate atherosclerosis and foam cells formation by

Development of an inflammation imaging tracer, 111In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE-/- atherosclerosis mouse model.

Science.gov (United States)

Wei, Lihui; Petryk, Julia; Gaudet, Chantal; Kamkar, Maryam; Gan, Wei; Duan, Yin; Ruddy, Terrence D

2018-02-07

Chemokine receptor 5 (CCR5) plays an important role in atherosclerosis. Our objective was to develop a SPECT tracer targeting CCR5 for imaging plaque inflammation by radiolabeling D-Ala-peptide T-amide (DAPTA), a CCR5 antagonist, with 111 In. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with 111 In. Cell uptake studies were conducted in U87-CD4-CCR5 and U87-MG cells. Biodistribution was determined in C57BL/6 mice. Autoradiography, en face and Oil Red O (ORO) imaging studies were performed in ApoE -/- mice. DOTA-DAPTA was radiolabeled with 111 In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). 111 In-DOTA-DAPTA exhibited fast blood and renal clearance and high spleen uptake. The U87-CD4-CCR5 cells had significantly higher uptake in comparison to the U87-MG cells. The cell uptake was reduced by three times with DAPTA, indicating the receptor specificity of the uptake. Autoradiographic images showed significantly higher lesion uptake of 111 In-DOTA-DAPTA in ApoE -/- mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE -/- high fat diet (HFD) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the CCR5 receptor. 111 In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.

Myocardial Ischaemia, Coronary Atherosclerosis and Pulmonary Pressure Elevation in Antiphospholipid Syndrome Patients.

Science.gov (United States)

Padjas, Agnieszka; Płazak, Wojciech; Celińska-Lowenhoff, Magdalena; Mazurek, Adam; Perricone, Carlo; Podolec, Piotr; Musiał, Jacek

2016-01-01

Thrombotic events in antiphospholipid syndrome (APS) involve venous and arterial circulation with the possible involvement of coronary or pulmonary microcirculation. To evaluate the influence of antiphospholipid antibodies (aPL) and on myocardial ischaemia assessed by single-photon emission computerized tomography (SPECT), coronary atherosclerosis assessed by multidetector computerized tomography (MDCT) and pulmonary pressure assessed by transthoracic echocardiography (TTE) in patients with primary antiphospholipid syndrome (PAPS). TTE, SPECT (Tc 99m sestamibi) and MDCT-based coronary calcium scoring were performed in 26 consecutive PAPS patients (20 females, 6 males, aged 20-61, mean 39.7) without any signs of other autoimmunological disease and without clinical symptoms of heart disease. Out of 26 patients, TEE showed normal left and right ventricle function in 25 (96.2%) and elevated (≥ 30 mm Hg) right ventricle systolic pressure in 7 (26.9%) patients. SPECT revealed myocardial perfusion defects in 15 (57.7%) patients: exercise-induced in 6 (23.1%) and persistent in 11 (42.3%). MDCT revealed coronary calcifications in 4 (15.4%) patients. The number of plaques ranged from 1 to 11 (median 2), volume 3-201.7 mm³ (median 7), calcium scores 1.3-202.6 (median 5.7). In the group with perfusion defects or coronary calcifications (n = 15), all the patients showed elevated aCL IgG. In most of the relatively young APS patients, without any symptoms of ischemic heart disease, SPECT showed myocardial perfusion defects, and coronary calcifications in 1/6 of them. Right ventricle systolic pressure was elevated in 1/4 of APS patients. These pathologies, well known as cardiovascular risk markers, were associated with elevated levels of the IgG class of both anti-cardiolipin and antiB2 GPI antibodies. Thus, in a high percentage of APS patients, clinically silent myocardial ischaemia, pulmonary pressure elevation and coronary atherosclerosis are present and related to the

Premature subclinical atherosclerosis in children and young adults with juvenile idiopathic arthritis

DEFF Research Database (Denmark)

Bohr, Anna-Helene; Fuhlbrigge, Robert C; Karup Pedersen, Freddy

2016-01-01

Many studies show that Juvenile Idiopathic Arthritis (JIA) is associated with early subclinical signs of atherosclerosis. Chronic inflammation per se may be an important driver but other known risk factors, such as dyslipidemia, hypertension, insulin insensitivity, a physically inactive lifestyle...

Effects of long- and short-term darbepoetin-α treatment on oxidative stress, inflammation and endothelial injury in ApoE knockout mice.

Science.gov (United States)

Özdemir, Evrim Dursun; Hanikoglu, Aysegul; Cort, Aysegul; Ozben, Beste; Suleymanlar, Gultekin; Ozben, Tomris

2017-07-01

Atherosclerosis and atherosclerosis-related complications are the main cause of death in the world. Vascular injury in response to inflammation and enhanced oxidant stress promotes endothelial dysfunction and leads to atherosclerotic lesions. Low-dose treatment with darbepoetin-α may be a potential therapeutic tool for endothelial injury and atherosclerosis. In order to study the effect of darbepoetin-α on endothelial injury and atherosclerosis, we used ApoE-/- mice as the atherosclerotic mice model. We monitored atherosclerosis and plaque formation histochemically in ApoE knockout mice at early and late stages of atherosclerosis. Darbepoetin-α was injected intraperitoneally at a dose of 0.1 μg/kg to ApoE-/- mice. The results of 2 ApoE-/- mice groups injected with darbepoetin-α (early and late stages of atherosclerosis) were compared to the results of the corresponding saline injected ApoE-/- mice groups and the control (C57BL/6) mice. Lipid profile (total cholesterol, triglyceride), inflammation (CRP, IL-6, histamine), endothelial injury (ICAM-1, selectin) and oxidative stress markers (lipid peroxidation, protein oxidation) were significantly increased in 4 atherosclerotic groups compared to the control group. Short-term darbepoetin-α had no marked effects on indicators of inflammation and endothelial injury in the ApoE knockout mice groups compared to the ApoE knockout mice not treated with darbepoetin-α, however, darbepoetin-α significantly decreased 8-isoprostane and protein carbonyl content. Long term darbepoetin-α treatment reduced oxidative stress in ApoE-/- mice. This study contributes to understanding and elucidating the biochemical changes occurring during early and late stages of atherosclerosis development regarding lipid profile, inflammation, endothelial injury and oxidative stress markers.

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

Energy Technology Data Exchange (ETDEWEB)

Foss, Catherine A., E-mail: cfoss1@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Bedja, Djahida [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Faculty of Medicine and Health Sciences, Macquarie University, Sydney (Australia); Mease, Ronnie C.; Wang, Haofan [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Kass, David A. [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Chatterjee, Subroto [Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Pomper, Martin G. [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)

2015-05-22

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.

Calcific shoulder joint periarthritis. Disappearance of calcifications after laser therapy

Energy Technology Data Exchange (ETDEWEB)

Gussetti, P; Moroso, P; Palazzo, C

1986-01-01

The authors report their results in the laser therapy of 30 calcific joint periarthritis. In two out of the ten radiographed cases, at the end of therapy, the complete disappearance of calcifications has been shown and in one case a decrease in calcification volume has been demonstrated. In the follow up after 6 months, 80% of clinically checked patients had no painful relapse.

Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

Directory of Open Access Journals (Sweden)

Connie Slocum

2014-07-01

Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals

DEFF Research Database (Denmark)

Ludvigsen, Trine Pagh; Kirk, Rikke Kaae; Christoffersen, Berit Østergaard

2015-01-01

in human patients, inclusion of this disease aspect in the characterization of a such model, is highly relevant. The objective of this study was to evaluate the effect of mild streptozotocin-induced diabetes on ex- and in vivo end-points in a diet-induced atherosclerotic minipig model. Castrated male...... Göttingen minipigs were fed standard chow (CD), atherogenic diet alone (HFD) or with superimposed mild streptozotocin-induced diabetes (HFD-D). Circulating markers of inflammation (C-reactive protein (CRP), oxidized low-density lipoprotein (oxLDL), plasminogen activator inhibitor-1, lipid and glucose......From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis...

High prevalence of subclinical atherosclerosis in Brazilian postmenopausal women with low and intermediate risk by Framingham score.

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Petisco, Ana Claudia Gomes Pereira; Assef, Jorge Eduardo; de Jesus, Carlos Alberto; Saleh, Mohamed Hassan; Barbosa, Jose Eduardo Martins; Costa de Souza Le Bihan, David; Pinto, Ibraim Masciarelli França; Rolim Fernandes Fontes Pedra, Simone; Barretto, Rodrigo Bellio de Mattos; Sousa, Amanda Guerra de Moraes Rego

2017-03-01

Cardiovascular diseases are the leading cause of mortality among women in several countries. Early detection of subclinical atherosclerosis (SA) could enable the adoption of preventive measures to avoid cardiovascular events. This study aimed to determine the prevalence of SA in Brazilian asymptomatic postmenopausal women in Framingham Risk Score (FRS) low and intermediate groups. Computed tomography (CT) and ultrasound (US) scans were performed in 138 asymptomatic postmenopausal women (56.1 ± 4.9 years of age) to survey for coronary artery and aortic calcification (CT scan) and assess carotid intima-media thickness (CIMT) and identify carotid plaques (US). The mean FRS was 2.64 ± 2.13 %. The prevalence of increased CIMT, carotid plaques, increased CIMT and/or plaques, coronary artery calcification (CAC) >0 and aortic calcification (AC) were, respectively, 45.7, 37.7, 62.3, 23.9 and 45.7 %. Normal imaging tests were found in 22.4 %. SA, defined as at least one abnormal imaging test, was associated with age, FRS, waist-to-rip ratio, systolic and diastolic blood pressure, HDL-c and ApoA1 levels, and ApoA1/ApoB ratio. In logistic regression, SA was associated with higher age (OR 1.108, 95 % CI 1.010-1.215, p = 0.029) and lower ApoA1 levels (OR 0.979, 95 % CI 0.960-0.998, p = 0.029). SA was prevalent in Brazilian postmenopausal women with low and intermediate risk groups (FRS) and was associated with higher age and lower levels of ApoA1. Carotid atherosclerosis was the most common presentation of SA in this group.

A Study of Carotid Intimomedial Thickness as a Primary Marker of Atherosclerosis in Patients with Rheumatoid Arthritis.

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Shivani Patel

2016-01-01

RA is a chronic disease associatedd with chronic subclinical inflammation. In view of the consequentr high risk of atherosclerosis seen in these patients CIMT may serve as an early surrogate marker of atherosclerosis. We can identify these high risk subgroups of patients with a simple, reliable, inexpensive, and non-invasive bedside carotid Doppler sonogram even in resource poor countries such as India. In our view physicians should be vigilant to identify and screen regularly for atherosclerosis with CIMT in RA patients, so that prompt early management can prevent the cardiovascular complications.

The Establishment and Characteristics of Rat Model of Atherosclerosis Induced by Hyperuricemia

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Zhen Liu

2016-01-01

Full Text Available Epidemiological studies have identified hyperuricemia as an independent risk factor for cardiovascular disease. However, the mechanism whereby hyperuricemia causes atherosclerosis remains unclear. The objective of the study was to establish a new rat model of hyperuricemia-induced atherosclerosis. Wistar-Kyoto rats were randomly allocated to either a normal diet (ND, high-fat diet (HFD, or high-adenine diet (HAD, followed by sacrifice 4, 8, or 12 weeks later. Serum uric acid and lipid levels were analyzed, pathologic changes in the aorta were observed by hematoxylin and eosin staining, and mRNA expression was evaluated by quantitative real-time polymerase chain reaction. Serum uric acid and TC were significantly increased in the HAD group at 4 weeks compared with the ND group, but there was no significant difference in serum uric acid between the ND and HFD groups. Aorta calcification occurred earlier and was more severe in the HAD group, compared with the HFD group. Proliferating cell nuclear antigen, monocyte chemotactic factor-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 mRNA levels were increased in the HFD and HAD groups compared with the ND group. This new animal model will be a useful tool for investigating the mechanisms responsible for hyperuricemia-induced atherosclerosis.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers.

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Zingg, Sarah; Collet, Tinh-Hai; Locatelli, Isabella; Nanchen, David; Depairon, Michèle; Bovet, Pascal; Cornuz, Jacques; Rodondi, Nicolas

2016-06-01

The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the

Hepatocellular calcification

DEFF Research Database (Denmark)

Ladefoged, Claus; Frifelt, J J

1987-01-01

Autopsy of a twenty year old girl dying from complications of renal and cardiac failure demonstrated severe hepatocellular calcification, a rare finding. The pathogenesis is thought to be a combination of dystrophic calcification caused by severe centrilobular necrosis and metastatic calcificatio...

Periodontitis-activated monocytes/macrophages cause aortic inflammation

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Miyajima, Shin-ichi; Naruse, Keiko; Kobayashi, Yasuko; Nakamura, Nobuhisa; Nishikawa, Toru; Adachi, Kei; Suzuki, Yuki; Kikuchi, Takeshi; Mitani, Akio; Mizutani, Makoto; Ohno, Norikazu; Noguchi, Toshihide; Matsubara, Tatsuaki

2014-01-01

A relationship between periodontal disease and atherosclerosis has been suggested by epidemiological studies. Ligature-induced experimental periodontitis is an adequate model for clinical periodontitis, which starts from plaque accumulation, followed by inflammation in the periodontal tissue. Here we have demonstrated using a ligature-induced periodontitis model that periodontitis activates monocytes/macrophages, which subsequently circulate in the blood and adhere to vascular endothelial cells without altering the serum TNF-α concentration. Adherent monocytes/macrophages induced NF-κB activation and VCAM-1 expression in the endothelium and increased the expression of the TNF-α signaling cascade in the aorta. Peripheral blood-derived mononuclear cells from rats with experimental periodontitis showed enhanced adhesion and increased NF-κB/VCAM-1 in cultured vascular endothelial cells. Our results suggest that periodontitis triggers the initial pathogenesis of atherosclerosis, inflammation of the vasculature, through activating monocytes/macrophages. PMID:24893991

HMGB1 in vascular diseases : Its role in vascular inflammation and atherosclerosis

NARCIS (Netherlands)

de Souza, A. W. S.; Westra, J.; Limburg, P. C.; Bijl, M.; Kallenberg, C. G. M.

2012-01-01

The nuclear protein high mobility group box 1 (HMGB1) has been suggested to be involved in the pathogenesis of several vascular diseases such as systemic vasculitis and atherosclerosis. In systemic vasculitides including ANCA-associated vasculitis and Kawasaki disease, serum HMGB1 levels are higher

Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

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Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

2012-02-01

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis

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Yuka Yokoyama

2018-04-01

Full Text Available Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS. The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day or high dose (two puffs/min for 120 min/day. We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox. Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

Genomic Analysis of Circulating Cells: A Window into Atherosclerosis

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Kang, Ju-Gyeong; Patino, Willmar D.; Matoba, Satoaki; Hwang, Paul M.

2006-01-01

Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. PMID:16781950

Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

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Uryga, Anna K; Bennett, Martin R

2016-04-15

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Radiological patterns of thyroid calcifications

International Nuclear Information System (INIS)

Lim, Jun; Sim, Do Chul; Park, Seog Hee; Kim, Choon Yul; Bahk, Yong Whee

1986-01-01

The purpose of this study was to analyse the various patterns of calcification demonstrated in the anterior and lateral neck roentgenograms of 213 unselected patients with thyroid enlargement. The patterns of thyroid calcifications were correlated with clinical, surgical and histological findings. The results were as follows: 1. Of 213 cases of thyroid enlargement, 180 cases were benign and 168 cases were female. 2. The calcification rate was high in the chronic thyroid enlargement. 3. The incidence of calcification was 30.2% in the malignancy and 17.2% in the benign disease. There was no calcification in the Hashimoto's disease. 4. The nodular calcification was demonstrated in the both benign and malignant disease but curvilinear calcification was predominantly seen in benign disease.

Matrix Gla Protein Polymorphisms are Associated with Coronary Artery Calcification in Men

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Crosier, Michael D.; Booth, Sarah L.; Peter, Inga; Dawson-Hughes, Bess; Price, Paul A.; O’Donnell, Christopher J.; Hoffmann, Udo; Williamson, Matthew K.; Ordovas, Jose M.

2009-01-01

Summary Matrix Gla protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). Our aim was to examine the cross-sectional association between MGP single nucleotide polymorphisms (SNPs) [rs1800802 (T-138C), rs1800801 (G-7A), and rs4236 (Ala102Thr)] and CAC. CAC was measured by multidetector computed tomography (MDCT), in older men and women of European descent, (n = 386; 60 to 80 y of age). Serum MGP was measured by radioimmunoassay. Linear, Tobit and Ordinal regression analyses all revealed that in men, homozygous carriers of the minor allele of rs1800802 , rs1800801 , or rs4236 (minor allele frequency: 21, 38, and 40%, respectively) were associated with a decreased quantity of CAC, relative to major allele carriers. This association was not found in women. Although genetic variation in MGP was associated with serum MGP concentrations, there were no associations between serum MGP and CAC. The results of this study suggest a role for MGP genetic variants in coronary atherosclerosis among men that is not reflected in serum MGP concentrations. PMID:19352064

Acute Retropharyngeal Calcific Tendinitis in an Unusual Location: a Case Report in a Patient with Rheumatoid Arthritis and Atlantoaxial Subluxation

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Lee, Seung Hun; Joo, Kyung Bin; Lee, Kyu Hoon; Uhm, Wan Sik [Hanyang University Hospital, Seoul (Korea, Republic of)

2011-08-15

Retropharyngeal calcific tendinitis is defined as inflammation of the longus colli muscle and is caused by the deposition of calcium hydroxyapatite crystals, which usually involves the superior oblique fibers of the longus colli muscle from C1-3. Diagnosis is usually made by detecting amorphous calcification and prevertebral soft tissue swelling on radiograph, CT or MRI. In this report, we introduce a case of this disease which was misdiagnosed as a retropharyngeal tuberculous abscess, or a muscle strain of the ongus colli muscle. No calcifications were visible along the vertical fibers of the longus colli muscle. The lesion was located anterior to the C4-5 disc, in a rheumatoid arthritis patient with atlantoaxial subluxation. Calcific tendinitis of the longus colli muscle at this location in a rheumatoid arthritis patient has not been reported in the English literature.

Growth Pattern of Atherosclerotic Calcifications

DEFF Research Database (Denmark)

Larsen, Lene Lillemark; Ganz, Melanie; Dam, Erik

2008-01-01

of the calcifications are matched longitudinally using thin plate spline registration and area overlap calculations. The growth of the calcifications is measured by the distribution of the geometry statistics of the calcifications. The method was evaluated on 135 subjects with a total number of 611 calcifications. Our...

Study of the position of calcification in calcific tendinitis of the shoulder

International Nuclear Information System (INIS)

Asakura, Toru; Matsuura, Koumei; Shin, Kunichika; Ooe, Kenjiro

2011-01-01

The commonly occurring position of calcification in the calcific tendinitis of the shoulder is said to be the supraspinatus tendon. In the anatomical field, it has been newly discovered that the infraspinatus tendon crosses over the supraspinatus tendon to the superior facet of the greater tuberosity. In this study, we thus attempted to determine the occurring position of calcification on MRI quantitatively. We measured the angle between the bicipital groove and center of calcification, and found it to be 49.5±16.5 degrees. On the other hand, it has been reported that the boundary line between the superior and middle facets is 45.4 degrees externally rotated from the bicipital groove. The protrusion formed at the greater tuberosity at this position imposes mechanical stress on the rotator cuff tendon. As we confirmed that these two angles are very close in this study, it suggests that calcification occurs at the boundary line of the superior and middle facets. Our findings also indicate that calcification often occurs at the infraspinatus tendon. (author)

Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

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Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

2015-08-01

Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; Ptriglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. © 2015 American Heart Association, Inc.

Regulation of the renin–angiotensin system in coronary atherosclerosis: A review of the literature

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Ramadan A Hammoud

2008-01-01

Full Text Available Ramadan A Hammoud, Christopher S Vaccari, Sameer H Nagamia, Bobby V KhanEmory University School of Medicine, Division of Cardiology, Grady Memorial Hospital Vascular Research Laboratory, Atlanta, Georgia, USAAbstract: Activation of the renin–angiotensin system (RAS is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.Keywords: angiotensin II, atherosclerosis, endothelium, inflammation, vasculature

PREVALENCE OF METABOLIC SYNDROME IN PATIENTS WITH PSORIATIC ARTHRITIS: ITS ASSOCIATION WITH INFLAMMATION AND SUBCLINICAL ATHEROSCLEROSIS

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E. I. Markelova

2016-01-01

Full Text Available Metabolic syndrome (MS is a cluster of metabolic disorders giving rise to atherosclerotic  cardiovascular diseases (CVD. The combination  of inflammatory activity and a high spread of traditional  risk factors (RF for CVD in patients with psoriatic arthritis (PsA permits them to be referred to as a higher cardiovascular risk group as compared to the general population.Objective: to estimate the spread of MS and its association with inflammation and subclinical atherosclerosis in patients with PsA.Subjects and methods. This investigation enrolled 128 patients with PsA (61.7% women and 38.3% men; their median age was 43 [34; 49.5] years; the duration of PsA and psoriasis – 7 [3; 13] and 15 [6; 26] years, respectively. There was a preponderance of patients with moderate (3.7 ≥ DAS > 2.4 and high (DAS > 3.7 disease activity: 33 (25.8% and 74 (57.8%, respectively. MS was diagnosed on the basis of the 2011 National  Guidelines of the Russian Cardiology Society for Cardiovascular Prevention.  All the patients underwent carotid Doppler ultrasound (CDU for the diagnosis of subclinical atherosclerosis. Results and discussion. MS was diagnosed in 49 (38.3% patients with PsA. The most common  MS criteria were abdominal  obesity in 72 (56.3% and dyslipidemia [an elevation of low-density lipoproteins (LDL  level in 101 (78.9%, and a decrease in high-density lipoproteins (HDL  level in 65 (50.8]. Hypertension was diagnosed in 32 (25%. 65 (50.8% patients were found to have subclinical atherosclerosis,  as evidenced by CDU.The patients with MS were older than those without this condition  (46 [43; 52] and 39 [31; 46] years, respectively; p < 0.0001. These groups did not differ in PsA duration (15 [7; 29] and 15 [5.5; 25] years respectively; p = 0.47. The patients with MS had higher DAS values (4.4 [3.2; 5.6] and 3.6 [2.5; 4.7], respectively; p = 0.02; mean intima media thickness (IMT  (0.78 [0.72; 0.86] and 0.73 [0.66; 0.77] mm; p < 0.0001 and

Procyanidins-crosslinked aortic elastin scaffolds with distinctive anti-calcification and biological properties.

Science.gov (United States)

Wang, Xiaoya; Zhai, Wanyin; Wu, Chengtie; Ma, Bing; Zhang, Jiamin; Zhang, Hongfeng; Zhu, Ziyan; Chang, Jiang

2015-04-01

Elastin, a main component of decellularized extracellular matrices and elastin-containing materials, has been used for tissue engineering applications due to their excellent biocompatibility. However, elastin is easily calcified, leading to the decrease of life span for elastin-based substitutes. How to inhibit the calcification of elastin-based scaffolds, but maintain their good biocompatibility, still remains significantly challenging. Procyanidins (PC) are a type of natural polyphenols with crosslinking ability. To investigate whether pure elastin could be crosslinked by PC with anti-calcification effect, PC was first used to crosslink aortic elastin. Results show that PC can crosslink elastin and effectively inhibit elastin-initiated calcification. Further experiments reveal the possible mechanisms for the anti-calcification of PC crosslinking including (1) inhibiting inflammation cell attachment, and secretion of inflammatory factors such as MMPs and TNF-α, (2) preventing elastin degradation by elastase, and (3) direct inhibition of mineral nucleation in elastin. Moreover, the PC-crosslinked aortic elastin maintains natural structure with high pore volume (1111 μL/g), large pore size (10-300 μm) and high porosity (75.1%) which facilitates recellularization of scaffolds in vivo, and displays excellent hemocompatibility, anti-thrombus and anti-inflammatory potential. The advantages of PC-crosslinked porous aortic elastin suggested that it can serve as a promising scaffold for tissue engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel navigation technique for the endodontic treatment of a molar with pulp canal calcification and apical pathology.

Science.gov (United States)

Shi, Xilin; Zhao, Shiyong; Wang, Weidong; Jiang, Qianzhou; Yang, Xuechao

2018-04-01

Apical periodontitis, the inflammation of periapical tissue, commonly requires root canal treatment to achieve apical healing. However, if it is accompanied by pulp canal calcification, the treatment becomes complicated, and locating the root canal can be challenging. This case report describes a novel approach for treating a molar with pulp canal calcification and apical pathology. Due to the risk of perforation during treatment, a digitally printed template was used to assist in accurately locating the root canal. After six months, the patient was asymptomatic and the periradicular radiolucency was gradually reducing in size. © 2017 Australian Society of Endodontology Inc.

Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries

International Nuclear Information System (INIS)

Chen, Wengen; Bural, Gonca G.; Torigian, Drew A.; Alavi, Abass; Rader, Daniel J.

2009-01-01

Atherosclerosis is a dynamic inflammatory disorder. The biological composition and inflammatory state of an atherosclerotic plaque, rather than the degree of stenosis or its size are the major determinants of acute clinical events. A noninvasive technique to detect vulnerable atherosclerotic plaque is critically needed. FDG-PET/CT, a combined functional and structural whole-body imaging modality, holds great potential for this purpose. FDG uptake in large arteries has been frequently observed and is associated with cardiovascular risk factors. FDG accumulates in plaque macrophages and uptake is correlated with macrophage density. It is known that vascular FDG uptake and calcification do not overlap significantly and changes of FDG uptake are common, suggesting that FDG uptake may represent a dynamic inflammatory process. It has been reported that vascular FDG uptake can be attenuated by simvastatin in patients, and by the antiinflammatory drug probucol in rabbits. Vascular FDG uptake has been linked to cardiovascular events in some preliminary studies. Data from basic sciences, and animal and clinical studies support the emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries in humans. (orig.)

[Macrophage activation in atherosclerosis. Message 1: Activation of macrophages normally and in atherosclerotic lesions].

Science.gov (United States)

Nikiforov, N G; Kornienko, V Y; Karagodin, V P; Orekhov, A N

2015-01-01

Macrophages play important role in initiation and progression of inflammation in atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti-inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In plaque macrophages demonstrate different phenotypes, and besides macrophage phenotypes could be changed. Phenotypes M1, M2, M4, Mhem, HA-mac, M(Hb) u Mox are described in the article. Ability of macrophages change their phenotype also considered.

Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

Directory of Open Access Journals (Sweden)

Sowers James R

2005-03-01

Full Text Available Abstract Background Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling. The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall. Results The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician – researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisioning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. Conclusion A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications.

Persistent low-grade inflammation and regular exercise

DEFF Research Database (Denmark)

Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund

2010-01-01

Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection ...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise....

Role of parnaparin in atherosclerosis.

Science.gov (United States)

Bonomini, Francesca; Taurone, Samanta; Parnigotto, Pierpaolo; Zamai, Loris; Rodella, Luigi F; Artico, Marco; Rezzani, Rita

2016-12-01

Atherosclerosis is characterized by a proliferation of vascular smooth muscle cells (VSMCs) and their migration to the intima, which induces thickening of the intima itself, but the mechanism remains poorly understood. Low molecular weight heparin (LMWH) inhibits the proliferation of VSMCs. Previous studies have shown that a LMWH, parnaparin (PNP), acts on the processes of atherogenesis and atheroprogression in experimental animal models. The aim of this study was to investigate the involvement of oxidative stress, inflammation and VSMCs in the regulation of vascular wall homeostasis. We also considered the possibility of restoring vascular pathological changes using PNP treatment. In order to evaluate vascular remodelling in this study we have analysed the morphological changes in aortas of an animal model of atherosclerosis, apolipoprotein E-deficient mice (ApoE-/-) fed with a normal or a western diet without treatment or treated with PNP. We also analysed, by immunohistochemistry, the expression of proteins linked to atherogenesis and atheroprogression - an enzyme involved in oxidative stress, iNOS, examples of inflammatory mediators, such as tumour necrosis factor alpha (TNF-α), interleukins 1 and 6 (IL-1 and IL-6), and markers of VSMC changes, in particular plasminogen activator inhibitor-1 and thrombospondin-1 (PAI-1 and TSP-1). Our results could suggest that PNP downregulates VSMC proliferation and migration, mediated by PAI-1 and TSP-1, and reduces inflammation and oxidative stress in vessels. These data suggested that LMWH, in particular PNP, could be a theoretically practical tool in the prevention of atherosclerotic vascular modification. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Clinical and imaging features associated with intracranial internal carotid artery calcifications in patients with ischemic stroke

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Yilmaz, Arda [Mersin University, Department of Neurology, Faculty of Medicine, Mersin (Turkey); Akpinar, Erhan [Hacettepe University, Department of Radiology, Faculty of Medicine, Ankara (Turkey); Topcuoglu, Mehmet Akif; Arsava, Ethem Murat [Hacettepe University, Department of Neurology, Faculty of Medicine, Ankara (Turkey)

2015-05-01

Intracranial internal carotid artery calcifications (ICAC), a frequent finding on imaging studies, are predictive of future stroke risk in population-based studies. The clinical significance of this observation among ischemic stroke patients is however less clear. In this study, we analyzed ICAC burden in relation to vascular risk factor profile, stroke etiology, and extent of craniocervical vascular calcifications in a consecutive series of ischemic stroke patients. The burden of ICAC was determined both on non-contrast CT and CT-angiography source images by semiquantitative scoring algorithms. The distribution of vascular risk factors, etiologic stroke subtype, and calcification burden in other craniocervical arteries was assessed among patients with no ICAC, mild-moderate ICAC, and severe ICAC. Of 319 patients included into the study, 28 % had no ICAC, 35 % had mild-moderate ICAC, and 37 % had severe ICAC on CT angiography. Independent factors associated with ICAC burden in multivariate analysis included age (p < 0.001), diabetes mellitus (p = 0.006), and coronary artery disease (p < 0.001). Furthermore, a stroke etiology of large artery atherosclerosis or cardioaortic embolism was significantly related to higher ICAC burden (p = 0.006). Patients with severe ICAC were more likely to harbor calcifications in other vascular beds (p < 0.001). All of these findings persisted when analyses were repeated with CT-based ICAC burden assessments. ICAC burden reflects a continuum of atherosclerotic disease involving carotid arteries together with other craniocervical vascular beds. ICAC is significantly associated with stroke of large vessel or cardioembolic origin. This information might help the clinician in prioritizing etiologic work-up in the acute period. (orig.)

Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits

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Ya-Mei Yu

2016-07-01

Full Text Available Atherosclerosis plays a key role in the development of cardiovascular diseases, and is often associated with oxidative stress and local inflammation. Thymol, a major polyphenolic compound in thyme, exhibits antioxidant and anti-inflammatory properties. In this study, we measured the in vitro antioxidant activity of thymol, and investigated the effect of thymol on high-fat-diet-induced hyperlipidemia and atherosclerosis. New Zealand white rabbits were fed with regular chow, high-fat and high-cholesterol diet (HC, T3, or T6 (HC with thymol supplementation at 3 mg/kg/d or 6 mg/kg/d, respectively for 8 weeks. Aortic intimal thickening, serum lipid parameters, multiple inflammatory markers, proinflammatory cytokines, and atherosclerosis-associated indicators were significantly increased in the HC group but decreased upon thymol supplementation. In summary, thymol exhibits antioxidant activity, and may suppress the progression of high-fat-diet-induced hyperlipidemia and atherosclerosis by reducing aortic intimal lipid lesion, lowering serum lipids and oxidative stress, and alleviating inflammation-related responses.

ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis : Results from the PERTINENT study

NARCIS (Netherlands)

Ceconi, C.; Fox, K.M.; Remme, W.J.; Simoons, M.L.; Deckers, J.W.; Bertrand, M.; Parrinello, G.; Kluft, C.; Blann, A.; Cokkinos, D.; Ferrari, R.

2009-01-01

The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha

Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.

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Josefin Skogsberg

2008-03-01

Full Text Available Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-Apo(100/100Mttp(flox/flox Mx1-Cre. Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.

Disconnect Between Adipose Tissue Inflammation and Cardiometabolic Dysfunction in Ossabaw Pigs

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Vieira-Potter, Victoria J.; Lee, Sewon; Bayless, David S.; Scroggins, Rebecca J.; Welly, Rebecca J.; Fleming, Nicholas J.; Smith, Thomas N.; Meers, Grace M.; Hill, Michael A.; Rector, R. Scott; Padilla, Jaume

2015-01-01

Objective The Ossabaw pig is emerging as an attractive model of human cardiometabolic disease due to its size and susceptibility to atherosclerosis, among other characteristics. Here we investigated the relationship between adipose tissue inflammation and metabolic dysfunction in this model. Methods Young female Ossabaw pigs were fed a western-style high-fat diet (HFD) (n=4) or control low-fat diet (LFD) (n=4) for a period of 9 months and compared for cardiometabolic outcomes and adipose tissue inflammation. Results The HFD-fed “OBESE” pigs were 2.5 times heavier (p<0.001) than LFD-fed “LEAN” pigs and developed severe obesity. HFD-feeding caused pronounced dyslipidemia, hypertension, insulin resistance (systemic and adipose) as well as induction of inflammatory genes, impairments in vasomotor reactivity to insulin and atherosclerosis in the coronary arteries. Remarkably, visceral, subcutaneous and perivascular adipose tissue inflammation (via FACS analysis and RT-PCR) was not increased in OBESE pigs, nor were circulating inflammatory cytokines. Conclusions These findings reveal a disconnect between adipose tissue inflammation and cardiometabolic dysfunction induced by western diet feeding in the Ossabaw pig model. PMID:26524201

Molecular and cellular mechanisms of aortic stenosis.

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Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

Vasoreactivity, Inflammation and vascular effects of Thiazolidinediones in Insulin resistance

NARCIS (Netherlands)

Martens, Fabrice Marcel Anne Clément

2006-01-01

In the pathophysiology of atherosclerosis, based on the respons to injury mechanism, the pathophysiological phenomenons endothelial dysfunction and inflammation are playing a pivitol role. Endothelial dysfunction is characterized by a shift towards reduced vasodilation, a pro-inflammatory state,

New modalities of ultrasound-based intima-media thickness, arterial stiffness and non-coronary vascular calcifications detection to assess cardiovascular risk.

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Flore, R; Ponziani, F R; Tinelli, G; Arena, V; Fonnesu, C; Nesci, A; Santoro, L; Tondi, P; Santoliquido, A

2015-04-01

Carotid intima-media thickness (c-IMT), arterial stiffness (AS) and vascular calcification (VC) are now considered important new markers of atherosclerosis and have been associated with increased prevalence of cardiovascular events. An accurate, reproducible and easy detection of these parameters could increase the prognostic value of the traditional cardiovascular risk factors in many subjects at low and intermediate risk. Today, c-IMT and AS can be measured by ultrasound, while cardiac computed tomography is the gold standard to quantify coronary VC, although concern about the reproducibility of the former and the safety of the latter have been raised. Nevertheless, a safe and reliable method to quantify non-coronary (i.e., peripheral) VC has not been detected yet. To review the most innovative and accurate ultrasound-based modalities of c-IMT and AS detection and to describe a novel UltraSound-Based Carotid, Aortic and Lower limbs Calcification Score (USB-CALCs, simply named CALC), allowing to quantify peripheral calcifications. Finally, to propose a system for cardiovascular risk reclassification derived from the global evaluation of "Quality Intima-Media Thickness", "Quality Arterial Stiffness", and "CALC score" in addition to the Framingham score.

The role of oxidative stress and NADPH oxidase in the pathogenesis of atherosclerosis

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Dorota Bryk

2017-01-01

Full Text Available Reactive oxygen species (ROS play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5 may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis.

Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

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Tomoko Kurita-Ochiai

2015-09-01

Full Text Available Periodontal disease is a highly prevalent disorder affecting up to 80% of the global population. Recent epidemiological studies have shown an association between periodontal disease and cardiovascular disease, as oxidative stress plays an important role in chronic inflammatory diseases such as periodontal disease and cardiovascular disease. In this review, we focus on the mechanisms by which periodontopathic bacteria cause chronic inflammation through the enhancement of oxidative stress and accelerate cardiovascular disease. Furthermore, we comment on the antioxidative activity of catechin in atherosclerosis accelerated by periodontitis.

Germinated Brown Rice Attenuates Atherosclerosis and Vascular Inflammation in Low-Density Lipoprotein Receptor-Knockout Mice.

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Zhao, Ruozhi; Ghazzawi, Nora; Wu, Jiansu; Le, Khuong; Li, Chunyang; Moghadasian, Mohammed H; Siow, Yaw L; Apea-Bah, Franklin B; Beta, Trust; Yin, Zhengfeng; Shen, Garry X

2018-05-02

The present study investigates the impact of germinated brown rice (GBR) on atherosclerosis and the underlying mechanism in low-density lipoprotein receptor-knockout (LDLr-KO) mice. The intensity of atherosclerosis in aortas of LDLr-KO mice receiving diet supplemented with 60% GBR (weight/weight) was significantly less than that in mice fed with 60% white rice (WR) or control diet ( p mice fed with WR diet was significantly more than that from mice receiving the control diet ( p mice in comparison to the WR diet ( p mice compared to WR. The anti-atherosclerotic effect of GBR in LDLr-KO mice at least in part results from its anti-inflammatory activity.

Diagnosis of calcification on abdominal radiographs

International Nuclear Information System (INIS)

Lamb, C.R.; Kleine, L.J.; McMillan, M.C.

1991-01-01

A wide variety of normal and pathologic factors may induce intraabdominal calcification. In general, the most reliable indication of the cause of a calcification is its location; therefore, if the affected organ can be identified the radiographic diagnosis is often straightforward or, at least, limited to relatively few possibilities. With this principle in mind, a series of patients with abdominal calcification are described for the purpose of illustrating the appearance of calcification of various abdominal organs. In addition, etiology for the calcification in each patient is discussed. Certain extraabdominal calcifications which may be seen on abdominal radiographs are also mentioned

Factors associated with early atherosclerosis and arterial calcifications in young subjects with a benign phenotype of obesity.

Science.gov (United States)

Gilardini, Luisa; Pasqualinotto, Lucia; Di Matteo, Silvia; Caffetto, Katherine; Croci, Marina; Girola, Andrea; Invitti, Cecilia

2011-08-01

We assessed (i) the association between early arterial disease and factors linked to adiposity, dietary habits, and family in a young cohort of 151 obese children and adolescents with less than or equal to one cardiovascular (CV) risk factor, (ii) whether in subjects with carotid calcifications there was an imbalance of calcium-phosphorus homeostasis. Measurement included: carotid ultrasound, oral glucose tolerance test, anthropometry, body composition, dietary history, white blood cells count, lipids, uric acid, adiponectin, insulin, C-reactive protein, plasminogen activator inhibitor 1 (PAI-1), 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium and phosphorus. Obese children with carotid artery intima media thickness (cIMT) values >75° percentile (0.55 mm), compared to those with lower cIMT, were more obese, more often pubertal and had higher prevalence of family history of CV disease (CVD) (P < 0.05), higher plasma PAI-1 and uric acid (P < 0.001) and lower adiponectin (P < 0.05) and high-density lipoprotein (HDL) cholesterol levels (P < 0.05). After adjustment for sex, age, puberty, obesity, and insulin levels, only PAI-I remained significantly different between the two groups (10.9 (7.2-29.8) vs. 6.2 (4.3-10.6) ng/ml, P < 0.001). Dietary intake did not affect cIMT values. Eight percent of subjects showed nonatherosclerotic carotid calcifications with patchy pattern. These children had a worse lipid profile (P < 0.05) and higher plasma PTH levels (48.6 ± 21.5 vs 38.5 ± 16.9 pg/ml, P < 0.05) that were inversely associated with 25-hydroxyvitamin D levels (r = 0.245, P < 0.01). Present results suggest that (i) several adiposity-related factors may play a role in promoting the development of early arterial diseases in young subjects with a benign phenotype of obesity, (ii) a PTH rise resulting from a subclinical imbalance in calcium-phosphorus homeostasis may affect the biological process of vascular calcifications.

Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke

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Yu-Chen Cheng

2017-01-01

Full Text Available Good nutrition could maintain health and life. Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs. They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide. In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation. The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects. Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress. Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity. Despite the numerous in vivo and in vitro studies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

NARCIS (Netherlands)

Lievens, Dirk; Eijgelaar, Wouter J.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Lutgens, Esther

2009-01-01

Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Science.gov (United States)

Lee, Stuart M. C.; Rana, Brinda K.; Stenger, Michael B.; Sears, Dorothy D.; Smith, Scott M.; Zwart, Sara R.; Macias, Brandon R.; Hargans, Alan R.; Sharma, Kumar; De Vivo, Immaculata

2017-01-01

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift

Association between gamma-glutamyltransferase and coronary artery calcification.

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Atar, Asli I; Yilmaz, Omer C; Akin, Kayihan; Selcoki, Yusuf; Er, Okan; Eryonucu, Beyhan

2013-08-20

The exact mechanisms behind the association between atherosclerosis and gamma-glutamyltransferase (GGT) are unclear. Coronary artery calcification (CAC) detected by computerized tomography is an important marker of atherosclerosis and its severity correlates with coronary plaque burden. The aim of this study was to investigate if serum GGT levels are associated with CAC in patients without known coronary heart disease (CHD) who had low-intermediate risk for CHD. Two hundred and seventy two patients who had low-intermediate risk for coronary artery disease were included in the study. Serum GGT levels were measured spectrophotometrically. CACS (Agatston method) were performed using a 64-slice computerized tomography scanner. The patients were grouped according to their GGT values in four quartiles. Patients in higher GGT quartiles had elevated CAC score (P<0.001). Patients in higher GGT quartiles were predominantly males (P<0.001) and were more likely to be smoking (P=0.004), and have elevated uric acid (P<0.001), fasting blood glucose (P<0.001), CRP levels (P=0.003) and 10-year total cardiovascular risk (P=0.007) and low HDL levels (P<0.001). Positive correlations were found between log GGT and CAC (r=0.233, P<0.001). In the multivariate analysis GGT, age, smoking and serum uric acid levels appeared as independent factors predictive of presence of CAC. We demonstrated a significant correlation between serum GGT levels and CAC and CHD risk factors. Serum GGT level was an independent marker of CAC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Genome-Wide Association Studies Candidate Gene to Dual Modifier of Nonalcoholic Steatohepatitis and Atherosclerosis

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Clint L. Miller, PhD

2016-12-01

Full Text Available Nonalcoholic steatohepatitis is a common disease involving chronic accumulation of fat and inflammation in the liver, often leading to advanced fibrosis, cirrhosis, and cancer. It is known that nonalcoholic steatohepatitis shares many features with atherosclerosis; however, there are still no effective therapeutics. In a recent study published in Nature, investigators demonstrated that mice lacking a high-density lipoprotein–associated gene were surprisingly protected from both steatohepatitis and atherosclerosis through the stabilization of the liver X receptor. This work reveals a timely candidate target for 2 highly prevalent cardiovascular diseases.

Thymoma calcification: Is it clinically meaningful?

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Alkaied Homam

2011-08-01

Full Text Available Abstract Among anterior mediastinal lesions, thymoma is the most common. Thymomas are tumors of thymic epithelial cell origin that are distinguished by inconsistent histological and biologic behavior. Chest imaging studies typically show a round or lobulated tumor in the anterior mediastinum. Calcifications in thymomas are classically punctuate or amorphous, positioned within the lesion. Chest computed tomography (CT features suggesting higher risk thymoma consist of tumor heterogeneity, vascular involvement, lobulation, pulmonary nodules, lymphadenopathy, and pleural manifestations. Imaging findings have an imperfect ability to predict stage and prognosis for thymoma patients. Our objective is to highlight the clinical implications of thymoma calcifications on the diagnosis, clinical manifestation and prognosis. A pubmed and google search was performed using the following words: thymoma calcification, calcified thymus, mediastinal calcification, anterior mediastinal calcification, and calcified thymoma. After reviewing 370 articles, 32 eligible articles describing thymoma calcifications were found and included in this review. Although the presence of thymus calcifications was more common in patients with invasive thymomas, they were present in significant portion of non-invasive thymomas. The presence of calcifications was not a significant factor in differentiating between benign and malignant thymoma. As a result, the type, location, size or other characteristics of thymus gland calcifications were not relevant features in clinical and radiologic diagnosis of thymoma. The histopathological diagnosis is still the only possible way to confirm the neoplastic nature of thymoma. All types of thymomas should be evaluated and managed independently of the presence of calcifications.

microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis.

Science.gov (United States)

Busch, Martin; Zernecke, Alma

2012-08-01

Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T cell responses with a complex picture emerging, in which miRNAs cooperate or antagonize DC behavior, thereby promoting or counterbalancing inflammatory responses. As miRNAs regulate key functions of DCs known to control atherosclerotic vascular disease, their potential as a therapeutic target holds promise and should be attended to in future research.

The relation between coronary artery calcification in asymptomatic subjects and both traditional risk factors and living in the city centre

DEFF Research Database (Denmark)

Lambrechtsen, J; Gerke, Oke; Egstrup, Kenneth

2012-01-01

atherosclerosis. The relationship between CAC and several demographic and clinical parameters were evaluated using multivariate logistic regression. Results:  A total of 1225 individuals participated in the study, of whom 250 (20%) were living in the centres of major Danish cities. Gender and age showed......Objective:  To evaluate the association between the risk factor of living in the city centre as a surrogate for air pollution and the presence of coronary artery calcification (CAC) in a population of asymptomatic Danish subjects. Design and subjects:  A random sample of 1825 men and women...

Animal Models of Calcific Aortic Valve Disease

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Krista L. Sider

2011-01-01

Full Text Available Calcific aortic valve disease (CAVD, once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

Effects of intra-abdominal sepsis on atherosclerosis in mice.

Science.gov (United States)

Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

2014-09-03

Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

Where Does Inflammation Fit?

Science.gov (United States)

Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

2017-09-01

This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

[Potential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis].

Science.gov (United States)

Camargo, Alejandra B; Manucha, Walter

Atherosclerosis, one of the main pathologic entities considered epidemic and a worldwide public health problem, is currently under constant review as regards its basic determining mechanisms and therapeutic possibilities. In this regard, all patients afflicted with the disease exhibit mitochondrial dysfunction, oxidative stress and inflammation. Interestingly, nitric oxide - a known vasoactive messenger gas - has been closely related to the inflammatory, oxidative and mitochondrial dysfunctional process that characterizes atherosclerosis. In addition, it has recently been demonstrated that alterations in the bioavailability of nitric oxide would induce the expression of heat shock proteins. This agrees with the use of functional foods as a strategy to prevent both vascular aging and the development of atherosclerosis. Finally, a greater knowledge regarding the mechanisms implied in the development of atherosclerosis will enable proposing new and possible hygiene, health and therapeutic interventions. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Reproducibility of coronary calcification detection with electron-beam computed tomography

International Nuclear Information System (INIS)

Hernigou, A.; Challande, P.; Boudeville, J.C.; Sene, V.; Grataloup, C.; Plainfosse, M.

1996-01-01

If coronary calcification scores obtained with electron-beam computed tomography (EBT) were proved to be correlated to coronary atherosclerosis, the reproducibility of the technique had to be assessed before being useed for patient follow-up. A total of 150 patients, selected as a result of a cholesterol screening programme, were studied by EBT. Twelve contiguous 3-mm-thick transverse slices beginning on the proximal coronary arteries were obtained through the base of the heart. The amount of calcium was evaluated as the calcified area weighted by a coefficient depending on the density peak level. The value was expressed as a logarithmic scale. Intra-observer, inter-observer and inter-examination reproducibilities were calculated. They were 1.9, 1.3 and 7.2%, respectively. These results were good enough to allow the use of EBT for longitudinal studies. The influence of acquisition and calculation conditions on score computation were also analysed. (orig.)

Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition.

Science.gov (United States)

Kutryb-Zajac, Barbara; Mateuszuk, Lukasz; Zukowska, Paulina; Jasztal, Agnieszka; Zabielska, Magdalena A; Toczek, Marta; Jablonska, Patrycja; Zakrzewska, Agnieszka; Sitek, Barbara; Rogowski, Jan; Lango, Romuald; Slominska, Ewa M; Chlopicki, Stefan; Smolenski, Ryszard T

2016-11-01

Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis. Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase 1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-) and wild-type mice as well as in human aortas. Plaques were analysed in the entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein Martius Scarlet Blue staining and vascular accumulation of macrophages. The cellular location of ecto-enzymes was analysed by immunofluorescence. The effect of eADA inhibition on atherosclerosis progression was studied by a 2-month deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already at the age of 1 month and progressed along atherosclerosis development, reaching a 10-fold difference at 10 months. The activity of eADA correlated with atherosclerotic changes in human aortas. High abundance of eADA in atherosclerotic vessels originated from activated endothelial cells and macrophages. There were no changes in ecto-nucleoside triphosphate diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice, suppressed vascular

Serum magnesium is inversely associated with coronary artery calcification in the Genetics of Atherosclerotic Disease (GEA) study.

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Posadas-Sánchez, Rosalinda; Posadas-Romero, Carlos; Cardoso-Saldaña, Guillermo; Vargas-Alarcón, Gilberto; Villarreal-Molina, María Teresa; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Medina-Urrutia, Aida; Jorge-Galarza, Esteban; Juárez-Rojas, Juan Gabriel; Torres-Tamayo, Margarita

2016-03-01

Serum magnesium is inversely associated to coronary artery calcification (CAC) in patients with chronic kidney disease. There is little information on this association in a general healthy population. The aim of this study was to examine the cross-sectional association of serum magnesium levels with CAC. We included 1276 Mexican-mestizo subjects (50 % women), aged 30-75 years, free of symptomatic cardiovascular disease. CAC was quantified by multidetector computed tomography using the method described by Agatston. Cross-sectional associations of serum magnesium with cardiometabolic factors and subclinical atherosclerosis defined as a CAC score > 0, were examined in logistic regression models adjusted for age, sex, education, smoking status, body mass index, systolic blood pressure, physical activity, elevated abdominal visceral tissue, fasting insulin and glucose, alcohol consumption, menopausal status (women only), low (LDL-C) and high density lipoprotein cholesterol (HDL-C), triglycerides, diuretic use, type 2 diabetes mellitus (DM2), and family history of DM2. After full adjustment, subjects in the highest quartile of serum magnesium had 48 % lower odds of hypertension (p = 0.028), 69 % lower odds of DM2 (p = 0.003), and 42 % lower odds of CAC score > 0 (p = 0.016) compared to those with the lowest serum magnesium. The analyses also showed that a 0.17 mg/dL (1SD) increment in serum magnesium was independently associated with 16 % lower CAC (OR 0.84, 95 % CI 0.724-0.986). In a sample of Mexican-mestizo subjects, low serum magnesium was independently associated to higher prevalence not only of hypertension and DM2, but also to coronary artery calcification, which is a marker of atherosclerosis and a predictor of cardiovascular morbidity and mortality.

Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

DEFF Research Database (Denmark)

Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

2018-01-01

Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle.

Science.gov (United States)

Moore, Stephanie N; Hawley, Gregory D; Smith, Emily N; Mignemi, Nicholas A; Ihejirika, Rivka C; Yuasa, Masato; Cates, Justin M M; Liu, Xulei; Schoenecker, Jonathan G

2016-01-01

Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary to discriminate

Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Xue, Shanshan [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 (China); Wang, Jiaxing [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Zhang, Xu; Shi, Ying; Li, Bochuan; Bao, Qiankun [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Pang, Wei [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Ai, Ding [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Zhu, Yi [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); He, Jinlong, E-mail: hejinlong@tmu.edu.cn [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)

2016-08-19

Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.

THE MAMMOGRAPHIC CALCIFICATIONS IN BREAST CANCER

Institute of Scientific and Technical Information of China (English)

Tang Ruiying; Liu Jingxian; Gaowen

1998-01-01

Objective: This study was performed to exam the relativeship between mammographic calcifications and breast cancer. Methods: All of the 184 patients with breast diseases underwent mammography before either an open biopsy or a mastectomy. The presence,morphology, and distribution of calcifications visualized on mammograms for breast cancer were compared with the controls who remained cancer free. Statistical comparisons were made by using the x2 test. Results:Of the 184 patients with breast diaeases, 93 malignant and 91 benign lesions were histologically confirmed.Calcifications were visualized on mammograms in 60(64%) of 93 breast cancers and 26 (28%) of 91 non breast cancers. The estimated odds ratio (OR) of breast cancer was 4.5 in women with calcifications seen on mammograms, compared with those having none (P＜0.01). Of the 60 breast carcinomas having mammographic calcifications, 28 (47%) were infiltrating ductal carcinomas.There were only 8 (24%) cases with infiltrating ductal cancers in the group of without calcifications seen on the mammograms (P＜0.05). Conclusion: Our finding suggests that mammographic calcification appears to be a risk factor for breast cancer. The granular and linear cast type calcification provide clues to the presence of breast cancer, especially when the carcinomas without associated masses were seen on mammograms.

Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis.

Directory of Open Access Journals (Sweden)

Kyoung Im Cho

Full Text Available Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS. We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR and major adverse cardiovascular events (MACE in patients with severe calcific AS.A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I and undergoing aortic valve replacement (AVR. We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period.The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR, 1.06; 95% confidence interval (CI, 1.04-1.09; p-value 9, respectively.The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS.

Beyond Framingham risk factors and coronary calcification: does aortic valve calcification improve risk prediction? The Heinz Nixdorf Recall Study.

Science.gov (United States)

Kälsch, Hagen; Lehmann, Nils; Mahabadi, Amir A; Bauer, Marcus; Kara, Kaffer; Hüppe, Patricia; Moebus, Susanne; Möhlenkamp, Stefan; Dragano, Nico; Schmermund, Axel; Stang, Andreas; Jöckel, Karl-Heinz; Erbel, Raimund

2014-06-01

Aortic valve calcification (AVC) is considered a manifestation of atherosclerosis. In this study, we investigated whether AVC adds to cardiovascular risk prediction beyond Framingham risk factors and coronary artery calcification (CAC). A total of 3944 subjects from the population based Heinz Nixdorf Recall Study (59.3±7.7 years; 53% females) were evaluated for coronary events, stroke, and cardiovascular disease (CVD) events (including all plus CV death) over 9.1±1.9 years. CT scans were performed to quantify AVC. Cox proportional hazards regressions and Harrell's C were used to examine AVC as event predictor in addition to risk factors and CAC. During follow-up, 138 (3.5%) subjects experienced coronary events, 101 (2.6%) had a stroke, and 257 (6.5%) experienced CVD events. In subjects with AVC>0 versus AVC=0 the incidence of coronary events was 8.0% versus 3.0% (pAVC scores (pAVC scores (3rd tertile) remained independently associated with coronary events (HR 2.21, 95% CI 1.28 to 3.81) and CVD events (HR 1.67, 95% CI 1.08 to 2.58). After further adjustment for CAC score, HRs were attenuated (coronary events 1.55, 95% CI 0.89 to 2.69; CVD events 1.29, 95% CI 0.83 to 2.00). When adding AVC to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (from 0.744 to 0.744) or CVD events (from 0.759 to 0.759). AVC is associated with incident coronary and CVD events independent of Framingham risk factors. However, AVC fails to improve cardiovascular event prediction over Framingham risk factors and CAC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Plasmacytoid dendritic cells: Development, functions, and role in atherosclerotic inflammation

Directory of Open Access Journals (Sweden)

Dimitry A Chistiakov

2014-07-01

Full Text Available Plasmacytoid dendritic cells (pDCs are a specialized subset of DCs that links innate and adaptive immunity. They sense viral and bacterial pathogens and release high levels of Type I interferons (IFN-I in response to infection. pDCs were shown to contribute to inflammatory responses in the steady state and in pathology. In atherosclerosis, pDCs are involved in priming vascular inflammation and atherogenesis through production of IFN-I and chemokines that attract inflammatory cells to inflamed sites. pDCs also contribute to the proinflammatory activation of effector T cells, cytotoxic T cells, and conventional DCs. However, tolerogenic populations of pDCs are found that suppress atherosclerosis-associated inflammation through down-regulation of function and proliferation of proinflammatory T cell subsets and induction of regulatory T cells with potent immunomodulatory properties. Notably, atheroprotective tolerogenic DCs could be induced by certain self-antigens or bacterial antigens that suggests for great therapeutic potential of these DCs for development of DC-based anti-atherogenic vaccines.

Persistent low-grade inflammation and regular exercise

DEFF Research Database (Denmark)

Åström, Maj-brit; Feigh, Michael; Pedersen, Bente Klarlund

2010-01-01

against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise.......Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...

Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

Science.gov (United States)

Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

2013-10-09

Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Phytosterols and atherosclerosis

DEFF Research Database (Denmark)

Schrøder, Malene

Cardiovascular disease (CVD) is the major cause of premature deaths worldwide. Coronary heart disease is the most common CVD, caused by atherosclerosis in the coronary arteries. Atherosclerosis is a multifactorial disease influenced by both genetic and environmental factors. WHO has in 2007 listed...... in its “Guidelines for assessment and management of cardiovascular risk” the following risk factors to influence progressive atherosclerosis: hypertension, abnormal blood lipids, diabetes, unhealthy diet, physical inactivity and smoking. Phytosterols (plant sterols and plant stanols) are known...... their blood cholesterol levels. The aim of this Ph.D. project was to investigate the effects of phytosterols on the development of atherosclerosis in the aorta of heterozygous Watanabe Heritable Hyperlipidemic (WHHL) rabbits. The main advantage of animal studies to human studies in atherosclerosis research...

Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.

Science.gov (United States)

Li, Melissa W; Mian, Muhammad Oneeb Rehman; Barhoumi, Tlili; Rehman, Asia; Mann, Koren; Paradis, Pierre; Schiffrin, Ernesto L

2013-10-01

Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

[Disk calcifications in children].

Science.gov (United States)

Schmit, P; Fauré, C; Denarnaud, L

1985-05-01

It is not unusual for intervertebral disk calcifications to be detected in pediatric practice, the 150 or so cases reported in the literature probably representing only a small proportion of lesions actually diagnosed. Case reports of 33 children with intervertebral disk calcifications were analyzed. In the majority of these patients (31 of 33) a diagnosis of "idiopathic" calcifications had been made, the cervical localization of the lesions being related to repeated ORL infections and/or trauma. A pre-existing pathologic factor was found in two cases (one child with juvenile rheumatoid arthritis treated by corticoids and one child with Williams and Van Beuren's syndrome). An uncomplicated course was noted in 31 cases, the symptomatology (pain, spinal stiffness and febricula) improving after several days. Complications developed in two cases: one child had very disabling dysphagia due to an anteriorly protruding cervical herniated disc and surgery was necessary; the other child developed cervicobrachial neuralgia due to herniated disc protrusion into the cervical spinal canal, but symptoms regressed within several days although calcifications persisted unaltered. These findings and the course of the rare complications documented in the literature suggest the need for the most conservative treatment possible in cases of disc calcifications in children.

NMR imaging of human atherosclerosis; Role de l`IRM dans le diagnostic d`atherosclerose

Energy Technology Data Exchange (ETDEWEB)

Toussaint, J.F. [Massachusetts General Hospital, Boston, MA (United States)]|[Hopital Cochin, 75 - Paris (France)

1995-12-31

Diagnosis and prognosis of atherosclerosis can no longer be evaluated with morphological parameters only. A description of atherosclerotic plaque composition is necessary to study the mechanisms of plaque rupture, which depends on collagenous cap and lipid core thicknesses. NMR, as a biochemical imaging technique, allows visualization of these components using T1 contrast (mobile lipids), T2 contrast (cap vs. core), spin density (calcifications), diffusion imaging, 1H and 13C spectroscopy. Today, these imaging sequences allow to study in vitro the effects of interventional techniques such as angioplasty or atherectomy. Clinical investigations begin, which will attempt to develop in vivo microscopy and test the ability of NMR to predict plaque rupture. (author). 13 refs., 7 figs.

Self-reported Sleep Duration and Subclinical Atherosclerosis in a General Population of Japanese Men

Science.gov (United States)

Suzuki, Sentaro; Arima, Hisatomi; Miyazaki, Soichiro; Fujiyoshi, Akira; Kadota, Aya; Takashima, Naoyuki; Hisamatsu, Takashi; Kadowaki, Sayaka; Zaid, Maryam; Torii, Sayuki; Horie, Minoru; Murata, Kiyoshi; Miura, Katsuyuki; Ueshima, Hirotsugu

2018-01-01

Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men. Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography. Results: The prevalence of CAC was 50.0% for participants with sleep duration 0.1). Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men. PMID:28747590

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

Science.gov (United States)

Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

2017-12-15

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Vascular and valvular calcifications in chronic hemodialysis patients

Directory of Open Access Journals (Sweden)

María Elena Bruzzone

2014-12-01

Full Text Available Introduction: Vascular and valvular calcifications are a frequent complication in dialyzed patients and are connected to an increased morbi-mortality. Many radiological methods (TAC multiple slices and with electrons emission have been used to investigate the presence of vascular calcifications in this population, but only few works have been focused on simple radiology. Objectives: The objectives of this work are to evaluate vascular calcifications by means of Kauppila index in hemodialysis prevalent patients, identify linked risk factors and determine their association with heart valves calcification. Methods: 95 stable patients under hemodialysis were surveyed during a period of 6 months longer. Abdominal Rx simple profile were performed on all patients to evaluate calcification of abdominal aorta by Kauppila index and twodimensional echocardiogram to detect valvular calcifications. Data were collected about sex, age, diabetes, Hypertension, tabaquism, dislipemia and bone-mineral metabolism. Results: 64.5% of the patients showed vascular calcifications. Average Kauppila index was 6.25. Age and time on dialysis correlated with vascular calcifications. In 31.6 % of individuals valvular calcifications were found, which presented significant association with diabetes and Kauppila Index. Conclusions: Vascular and valvular calcifications were frequent in the surveyed population. Kauppila index correlated with age, time on dialysis and valvular calcifications. Heart valves calcification was associated with diabetes.

Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese.

Science.gov (United States)

Nang, Ei Ei Khaing; van Dam, Rob M; Tan, Chuen Seng; Mueller-Riemenschneider, Falk; Lim, Yi Ting; Ong, Kai Zhi; Ee, Siqing; Lee, Jeannette; Tai, E Shyong

2015-01-01

Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed. This was a cross-sectional study of 398 Chinese participants (192 men and 206 women) from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman's correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis. In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day) was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93) but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31) after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations. Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation.

Fusobacterium nucleatum Alters Atherosclerosis Risk Factors and Enhances Inflammatory Markers with an Atheroprotective Immune Response in ApoE(null Mice.

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Irina M Velsko

Full Text Available The American Heart Association supports an association between periodontal disease (PD and atherosclerotic vascular disease (ASVD but does not as of yet support a causal relationship. Recently, we have shown that major periodontal pathogens Porphyromonas gingivalis and Treponema denticola are causally associated with acceleration of aortic atherosclerosis in ApoEnull hyperlipidemic mice. The aim of this study was to determine if oral infection with another significant periodontal pathogen Fusobacterium nucleatum can accelerate aortic inflammation and atherosclerosis in the aortic artery of ApoEnull mice. ApoEnull mice (n = 23 were orally infected with F. nucleatum ATCC 49256 and euthanized at 12 and 24 weeks. Periodontal disease assessments including F. nucleatum oral colonization, gingival inflammation, immune response, intrabony defects, and alveolar bone resorption were evaluated. Systemic organs were evaluated for infection, aortic sections were examined for atherosclerosis, and inflammatory markers were measured. Chronic oral infection established F. nucleatum colonization in the oral cavity, induced significant humoral IgG (P=0.0001 and IgM (P=0.001 antibody response (12 and 24 weeks, and resulted in significant (P=0.0001 alveolar bone resorption and intrabony defects. F. nucleatum genomic DNA was detected in systemic organs (heart, aorta, liver, kidney, lung indicating bacteremia. Aortic atherosclerotic plaque area was measured and showed a local inflammatory infiltrate revealed the presence of F4/80+ macrophages and CD3+ T cells. Vascular inflammation was detected by enhanced systemic cytokines (CD30L, IL-4, IL-12, oxidized LDL and serum amyloid A, as well as altered serum lipid profile (cholesterol, triglycerides, chylomicrons, VLDL, LDL, HDL, in infected mice and altered aortic gene expression in infected mice. Despite evidence for systemic infection in several organs and modulation of known atherosclerosis risk factors, aortic

Intake of traditional Inuit diet vary in parallel with inflammation as estimated from YKL-40 and hsCRP in Inuit and non-Inuit in Greenland

DEFF Research Database (Denmark)

Schæbel, Louise Holm; Vestergaard, H; Laurberg, Peter Marvin

2013-01-01

Chronic low-grade inflammation is involved in the initiation and progression of atherosclerosis and ischemic heart disease. This was rare in pre-western Inuit who lived on a diet that consisted mainly of marine mammals rich in n-3 fatty acids.......Chronic low-grade inflammation is involved in the initiation and progression of atherosclerosis and ischemic heart disease. This was rare in pre-western Inuit who lived on a diet that consisted mainly of marine mammals rich in n-3 fatty acids....

Intracranial calcification on paediatric computed tomography

International Nuclear Information System (INIS)

Kendall, B.; Cavanagh, N.

1986-01-01

An analysis of the computed tomograms of 18000 children examined consecutively form the basis of an assessment of the diagnostic significance of intracranial calcification. The low incidence of physiological calcification in the pineal and choroid of about 2% up to the age of 8 years, but increasing 5-fold by the age of 15 years, is confirmed. Pathological calcification occurred in 1.6%, the commonest causes being neoplasms (43%), neuroectodermal syndromes (20%) and infections (12%). Diffuse basal ganglia calcification (15%) bore little relation to the diverse clinical symptomatology, and routine bio-chemical studies showed a disorder of metabolism to be present in only 6 cases. Calcification has not been previously noted in acute haemorrhagic leukoencephalitis, Pertussis or Cocksackie encephalitis, infantile neuraxonal dystrophy, Marinesco-Sjoegren syndrome or in the basal ganglia in neurofibromatosis. (orig.)

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

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Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Association of the C-Reactive Protein Gene (CRP rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis

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Ewa Wypasek

2015-10-01

Full Text Available Elevation in C-reactive protein (CRP levels have been shown in patients with aortic valve stenosis (AS. Minor allele of the CRP gene (CRP rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96 vs. 1.68 (0.98–2.90 mg/L, p < 0.001 and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01 compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

Intracranial calcification in central diabetes insipidus

International Nuclear Information System (INIS)

Al-Kandari, Salwa R.; Pandey, Tarun; Badawi, Mona H.

2008-01-01

Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification. (orig.)

Intracranial calcification in central diabetes insipidus

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Al-Kandari, Salwa R. [Al Razi Hospital, Department of Clinical Radiology, Kuwait (Kuwait); Pandey, Tarun [Al Razi Hospital, Department of Clinical Radiology, Kuwait (Kuwait); University of Arkansas for Medical Sciences, Radiology Department, Little Rock, AR (United States); Badawi, Mona H. [Al-Adan Hospital, Department of Paediatrics, Kuwait (Kuwait)

2008-01-15

Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification. (orig.)

Quantitative X-ray CT analysis of calcification of the abdominal aorta and its relationship to obesity

International Nuclear Information System (INIS)

Shinagawa, Toshio; Hiraiwa, Yoshio; Mizuno, Seio; Kusunoki, Norio; Nitta, Yu; Matsubara, Takao; Iwainaka, Yoichi; Konishi, Hideo

1992-01-01

Quantitative analysis of abdominal aorta calcification by X-ray CT is useful method for non-invasive diagnosis of atherosclerosis. We recently examined the relationship between the X-ray CT measurement of abdominal aorta calcification and the degree of obesity. For this purpose, the body mass index (BMI) and the subcutaneous fat thickness (determined by X-ray CT at the umbilical level) were analyzed in relation to the abdominal aorta calcification index (ACI) in 845 patients (453 males and 392 females aged 40-79 years). Patients with BMI under 20 were classified as 'lean', those with BMI between 20-26 as 'normal' and those with BMI over 26 as 'obese'. 1. Among males, the ACI was highest in lean individuals and lowest in obese individuals. The difference in ACI between lean and obese males was significant in the middle aged group (40-65 years). Among females, no relationship was observed between the degree of obesity and ACI. 2. Among males, ACI was higher in individuals with low subcutaneous fat thickness and lower in individuals with greater subcutaneous fat thickness. The difference was significant in the middle aged group. Among females, no relationship was observed between the two parameters. 3. When the visceral fat to subcutaneous fat ratio (V/S) in 85 males and females aged 60-69 years was analyzed in relation to ACI, ACI tended to decrease as the V/S increased, in both males and females. 4. Relationships between BMI and subcutaneous fat thickness, between BMI and lipids and between lipids and ACI were also analyzed. (author)

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis

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Chung-Wei Kao

2018-05-01

Full Text Available Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs, which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2-binding motif of monocytes chemoattractant protein-1 (MCP-1 as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice, the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS imaging and magnetic resonance imaging (MRI. We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

Coronary artery calcification correlates with the presence and severity of valve calcification.

Science.gov (United States)

Koulaouzidis, G; Nicoll, R; MacArthur, T; Jenkins, P J; Henein, M Y

2013-10-15

To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both. This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score. AVC was more prevalent than MAC (64% vs. 2.5%, p AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC. The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification. © 2013.

Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke

DEFF Research Database (Denmark)

Holm, Sverre; Ueland, Thor; Dahl, Tuva B

2011-01-01

Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke....

Calcification in large cell neuroendocrine carcinoma of the lung

International Nuclear Information System (INIS)

Takamochi, Kazuya; Yokose, Tomoyuki; Ochiai, Atsushi; Yoshida, Junji; Nishimura, Mitsuyo; Ohmatsu, Hironobu; Nagai, Kanji; Nishiwaki, Yutaka

2003-01-01

The aim was to investigate the prevalence of intratumoral calcification in large cell neuroendocrine carcinoma (LCNEC) and to review computed tomography (CT) and histological findings. From August 1992 through March 2000, 35 out of 1183 surgically resected lung cancer patients were histologically diagnosed as having LCNEC at our institute. We reviewed the pain radiographs and CT scans of these 35 LCNEC patients. In LCNEC cases with intratumoral calcification, we examined the size, number, distribution and pattern of intratumoral calcifications visible on the CT scans and the histological features. Three cases (9%) exhibited calcification. The calcifications were recognized by CT scans alone. The CT scans showed punctate or eccentric intratumoral calcifications, which are considered to be a malignant feature, in all three cases. In two cases, the calcifications were histologically confirmed to be located within the necrotic areas of a tumor nest. We found three LCNEC cases with intratumoral calcification. The prevalence of LCNEC calcification was similar to that in previous reports on lung cancer. The mechanism of the intratumoral calcification in our LCNEC cases is speculated to be dystrophic calcification. (author)

Cardiac and pericardial calcifications on chest radiographs

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Ferguson, E.C., E-mail: ecferguson@hotmail.co [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Section of Thoracic Imaging, Houston, TX 77030 (United States); Berkowitz, E.A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Section of Thoracic Imaging, Houston, TX 77030 (United States)

2010-09-15

Many types of cardiac and pericardial calcifications identified on chest radiographs can be recognized and distinguished based on characteristic locations and appearances. The purpose of this review is to emphasize the importance of detecting cardiac and pericardial calcifications on chest radiographs, and to illustrate and describe the various types of calcifications that may be encountered and how they may be differentiated from one another. Each type of cardiac and pericardial calcification is discussed, its location and appearance described, and its significance explained. Recognizing and understanding these calcifications is important as they are often encountered in daily practice and play an important role in patient care.

Psychosocial predictors of coronary artery calcification progression in postmenopausal women.

Science.gov (United States)

Low, Carissa A; Matthews, Karen A; Kuller, Lewis H; Edmundowicz, Daniel

2011-01-01

Coronary artery calcification (CAC) has been associated with psychosocial factors in some but not all cross-sectional analyses. The goal of this study was to determine whether positive and negative psychosocial factors prospectively predict CAC progression in postmenopausal women. Participants from the Healthy Women Study who also participated in the Pittsburgh Mind-Body Center protocol (n = 149) completed self-report psychosocial measures before two electron beam computed tomographic scans of CAC separated by an average of 3.3 years. Results of exploratory factor analysis were used to create aggregate psychosocial indices: psychological risk (depressive symptoms, perceived stress, cynicism, and anger-in) and psychosocial resources (optimism, purpose in life, mastery, self-esteem, and social support). The psychological risk index predicted significantly greater CAC progression over 3 years (β = 0.16, p = .035, ΔR(2) = 0.03), whereas the psychosocial resources index was not predictive of CAC progression (β = -0.08, p = .30, ΔR(2) = 0.01). On individual scales, higher scores on cynicism emerged as a significant predictor of CAC progression, along with a trend linking anger-in to atherosclerosis progression. A post hoc analysis showed a significant interaction between cynicism and anger-in (β = 0.20, p = .01, ΔR(2) = 0.03), such that women reporting high levels of both cynicism and anger suppression exhibited the most CAC progression. These findings highlight psychosocial risk factors that may accelerate the progression of subclinical atherosclerosis in older women, suggest the potential importance of examining combinations of psychosocial risk factors, and identify potential targets for psychological interventions to reduce cardiovascular risk.

C-reactive protein and other markers of inflammation in hemodialysis patients

Science.gov (United States)

Heidari, Behzad

2013-01-01

Hemodialysis patients are at greater risk of cardiovascular disease. Higher than expected cardiovascular morbidity and mortality in this population has been attributed to dislipidemia as well as inflammation. The causes of inflammation in hemodialysis patients are multifactorial. Several markers were used for the detection of inflammatory reaction in patients with chronic renal disease. These markers can be used for the prediction of future cardiovascular events. Among the several parameters of inflammatory markers, serum, CRP is well known and its advantages for the detection of inflammation and its predictor ability has been evaluated in several studies. This review addressed the associated factors and markers of inflammation in hemodialysis patients. In addition, their ability in predicting future atherosclerosis and effect of treatment has been reviewed. However, this context particularly in using CRP as a prediction marker of inflammation and morbidity requires further studies. PMID:24009946

C-reactive protein and other markers of inflammation in hemodialysis patients.

Science.gov (United States)

Heidari, Behzad

2013-01-01

Hemodialysis patients are at greater risk of cardiovascular disease. Higher than expected cardiovascular morbidity and mortality in this population has been attributed to dislipidemia as well as inflammation. The causes of inflammation in hemodialysis patients are multifactorial. Several markers were used for the detection of inflammatory reaction in patients with chronic renal disease. These markers can be used for the prediction of future cardiovascular events. Among the several parameters of inflammatory markers, serum, CRP is well known and its advantages for the detection of inflammation and its predictor ability has been evaluated in several studies. This review addressed the associated factors and markers of inflammation in hemodialysis patients. In addition, their ability in predicting future atherosclerosis and effect of treatment has been reviewed. However, this context particularly in using CRP as a prediction marker of inflammation and morbidity requires further studies.

Topical thrombin-related corneal calcification.

Science.gov (United States)

Kiratli, Hayyam; Irkeç, Murat; Alaçal, Sibel; Söylemezoğlu, Figen

2006-09-01

To report a highly unusual case of corneal calcification after brief intraoperative use of topical thrombin. A 44-year-old man underwent sclerouvectomy for ciliochoroidal leiomyoma, during which 35 UNIH/mL lyophilized bovine thrombin mixed with 9 mL of diluent containing 1500 mmol/mL calcium chloride was used. From the first postoperative day, corneal and anterior lenticular capsule calcifications developed, and corneal involvement slightly enlarged thereafter. A year later, 2 corneal punch biopsies confirmed calcification mainly in the Bowman layer. Topical treatment with 1.5% ethylenediaminetetraacetic acid significantly restored corneal clarity. Six months later, a standard extracapsular cataract extraction with intraocular lens placement improved visual acuity to 20/60. This case suggests that topical thrombin drops with elevated calcium concentrations may cause acute corneal calcification in Bowman layer and on the anterior lens capsule.

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

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Lianxiang Bi

2017-12-01

Full Text Available Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Calcifications in the breast in Filaria loa infection

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Novak, R. (Karolinska Sjukhuset, Stockholm (Sweden). Dept. of Diagnostic Radiology)

A 40-year-old patient underwent mammography for evaluation of a mass. Atypical calcifications were observed in the opposite breast. Two types of calcification were observed: One type was spiral-shaped and the other type rod-shaped. These calcifications were caused by Filaria loa. Parasitic calcifications in the breast are uncommon. (orig.).

Vascular Adventitia Calcification and Its Underlying Mechanism.

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Na Li

Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese.

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Ei Ei Khaing Nang

Full Text Available Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed.This was a cross-sectional study of 398 Chinese participants (192 men and 206 women from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman's correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis.In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93 but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31 after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations.Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation.

Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis

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Erdi Sozen

2014-01-01

Full Text Available Atherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1 and modulates matrix metalloproteinase (MMP induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1 related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36 mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun.

Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

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Sharifah Intan Qhadijah Syed Ikmal

2013-01-01

Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

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Elham Khanicheh

Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

Isolated splenic calcifications in two patients with portal hypertension

International Nuclear Information System (INIS)

Aleixandre, A.; Cugat, A.; Ruiz, A.; Marti-Bonmati, L.; Tardaguila, F.

2002-01-01

Calcification of the walls of the veins of the portal hypertension (PHT) (1-0), is uncommon. Calcification of the intra splenic vessels is exceptional. We report two cases of isolated calcification of intra splenic vessels, without calcification of the splenoportal venous axis, in patients with liver cirrhosis and PHT. The calcification was not clear. Computed tomography identified the calcification as linear tubular, branched structures located in the wall of intra splenic vessels. magnetic resonance imaging disclosed signs of cirrhosis and PHT but did not show the splenic classifications because of technical limitations. The cause of these calcifications was sustained PHT due to chronic liver disease. (Author) 15 refs

Lack of Correlation Between Depression and Coronary Artery Calcification in a Non-Selected Danish Population

DEFF Research Database (Denmark)

Devantier, Torben Albert; Nørgaard, Bjarne Linde; Sand, Niels Peter

2013-01-01

BACKGROUND: Depression is associated with coronary artery disease, and atherosclerosis seems to play a central role in this relation. In several studies, multislice computed tomography (CT) has been applied for detection and quantification of coronary artery calcification (CAC) in relation...... to depression. To our knowledge, only one previous study has investigated the relation between CAC and depression in an unselected population. METHODS: A total of 617 persons were randomly selected from the background population. The participants underwent CT of the heart and were screened for depression by use...... of the Major Depression Inventory questionnaire. Quantification of CAC was performed using the Agatston method. The Mann-Whitney U test, Spearman's correlational analysis, and logistic regression were used to assess the association between depression and CAC. RESULTS: The median Agatston score...

Platelets and their chemokines in atherosclerosis – clinical applications

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Philipp evon Hundelshausen

2014-08-01

Full Text Available The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis i.e. stroke and myocardial infarction are definable but not the plaque burden.Platelet indices including platelet count and mean platelet volume and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities e.g. altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1bα, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation

Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

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Sattar Naveed

2011-01-01

Full Text Available Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666 recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father's occupation, childhood home status (owner-occupier; overcrowding and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P P Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father's occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the 'health divide' requires that these life course determinants are taken into account.

Calcification of peritoneal carcinomatosis from gastric carcinoma

International Nuclear Information System (INIS)

Matsuoka, Y.; Itai, Y.; Ohtomo, K.; Nishikawa, J.; Sasaki, Y.

1991-01-01

Peritoneal calcification is noted in peritoneal dissemination from serious cystoadenocarcinoma of the ovary, pseudomyxoma peritonei and meconium peritonitis. This article discusses a case of peritoneal disseminated calcification from gastric carcinoma. To the author's knowledge, this is the first report in English literature of gastric cancer showing peritoneal calcification. (author). 10 refs.; 1 fig

Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice

DEFF Research Database (Denmark)

Koenen, RR; Hundelshausen, P; Nesmelova, IV

2009-01-01

Atherosclerosis is characterized by chronic inflammation of the arterial wall due to chemokine-driven mononuclear cell recruitment. Activated platelets can synergize with chemokines to exacerbate atherogenesis; for example, by deposition of the chemokines platelet factor-4 (PF4, also known as CXC...... monocyte recruitment and reducing atherosclerosis without the aforementioned side effects. These results establish the in vivo relevance of chemokine heteromers and show the potential of targeting heteromer formation to achieve therapeutic effects......) and RANTES (CCL5), triggering monocyte arrest on inflamed endothelium. Homo-oligomerization is required for the recruitment functions of CCL5, and chemokine heteromerization has more recently emerged as an additional regulatory mechanism, as evidenced by a mutual modulation of CXCL8 and CXCL4 activities...... compromise systemic immune responses, delay macrophage-mediated viral clearance and impair normal T cell functions. Here we determined structural features of CCL5-CXCL4 heteromers and designed stable peptide inhibitors that specifically disrupt proinflammatory CCL5-CXCL4 interactions, thereby attenuating...

Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

Science.gov (United States)

Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

2010-01-01

Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

Atherosclerosis of the carotid artery: evaluation by magnetic resonance angiography.

Science.gov (United States)

Wildy, K S; Yuan, C; Tsuruda, J S; Ferguson, M S; Wen, N; Subramaniam, D S; Strandness, D E

1996-01-01

Carotid artery atherosclerotic plaques (APs) can lead to brain ischemia, an event shown to correlate with both the degree of stenosis and the composition of the AP. Currently, accurate estimates of stenosis can be obtained by either x-ray angiography or three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA). Our purpose was to determine whether three-dimensional TOF MRA images could also provide information on plaque location, morphology, and composition. Seven pre-endarterectomy patients underwent three-dimensional TOF MRA. After endarterectomy, plaque histology was evaluated. Three-dimensional TOF MRA images contained sufficient soft tissue contrast to differentiate the plaques from the surrounding tissues in all cases. Estimation of plaque morphology had 80% correlation with histology. Finally, intraplaque hemorrhage and calcification were deplicted as regions of moderately high and very low intensity, respectively. These preliminary results suggest that three-dimensional TOF MRA may be useful in studying the development and progression of carotid atherosclerosis.

Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

Science.gov (United States)

Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-01-14

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

Carotid intima-media thickness and calcification in relation to bone mineral density in postmenopausal women-the OSTPRE-BBA study.

Science.gov (United States)

Värri, Miika; Tuomainen, Tomi-Pekka; Honkanen, Risto; Rikkonen, Toni; Niskanen, Leo; Kröger, Heikki; Tuppurainen, Marjo T

2014-08-01

Atherosclerosis (AS) and osteoporosis are common diseases in elderly people and may be metabolically related. The aim of this cross-sectional population-based study was to explore the association between common carotid artery intima-media thickness (cIMT), carotid artery calcification (CAC), and BMD in postmenopausal women. In addition, the association of postmenopausal hormone therapy (HT) and selected diseases with cIMT and carotid calcification was studied. The 290 women (mean age 73.6 years) included in this Bone Brain Atherosclerosis study (OSTPRE-BBA) were randomly selected from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort, Finland. For this cross-sectional study, cIMT was measured with B-mode ultrasound; femoral neck and total body BMD were measured with dual-energy X-ray absorptiometry. There were no statistically significant associations between mean cIMT and femoral neck T-score (p>0.05). However, an increased maximum cIMT was significantly associated with low femoral neck T-score. In the osteoporotic group (T-score -1, n=122), it was 1.93±0.64mm (p=0.001). The odds of having CAC were approximately four-fold higher in the osteoporotic group compared with the group with a normal femoral neck T-score (odds ratio [OR]=4.2, p=0.038). The maximum cIMT was smaller in HT users (1.98±0.56mm, n=190) than in non-users (2.16±0.74mm, n=156, p=0.036). The results of our population-based study suggest that BMD is related to AS, at least in carotid arteries. They indirectly support the hypothesis of partially shared pathophysiological mechanisms between these two disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bovine pericardium coated with biopolymeric films as an alternative to prevent calcification: In vitro calcification and cytotoxicity results

International Nuclear Information System (INIS)

Nogueira, Grinia M.; Rodas, Andrea C.D.; Weska, Raquel F.; Aimoli, Cassiano G.; Higa, Olga Z.; Maizato, Marina; Leiner, Adolfo A.; Pitombo, Ronaldo N.M.; Polakiewicz, Bronislaw; Beppu, Marisa M.

2010-01-01

Bovine pericardium, for cardiac valve fabrication, was coated with either chitosan or silk fibroin film. In vitro calcification tests of coated and non coated bovine pericardium were performed in simulated body fluid solution in order to investigate potential alternatives to minimize calcification on implanted heart valves. Complementary, morphology was assessed by scanning electron microscopy - SEM; X-ray diffraction (XRD) and infrared spectroscopy (FTIR-ATR) were performed for structural characterization of coatings and biocompatibility of chitosan. Silk fibroin films were assayed by in vitro cytotoxicity and endothelial cell growth tests. Bovine pericardium coated with silk fibroin or chitosan did not present calcification during in vitro calcification tests, indicating that these biopolymeric coatings do not induce bovine pericardium calcification. Chitosan and silk fibroin films were characterized as non cytotoxic and silk fibroin films presented high affinity to endothelial cells. The results indicate that bovine pericardium coated with silk fibroin is a potential candidate for cardiac valve fabrication, since the affinity of silk fibroin to endothelial cells can be explored to induce the tissue endothelization and therefore, increase valve durability by increasing their mechanical resistance and protecting them against calcification.

Imaging pathobiology of carotid atherosclerosis with ultrasmall superparamagnetic particles of iron oxide: an update.

Science.gov (United States)

Sadat, Umar; Usman, Ammara; Gillard, Jonathan H

2017-07-01

To provide brief overview of the developments regarding use of ultrasmall superparamagnetic particles of iron oxide in imaging pathobiology of carotid atherosclerosis. MRI is a promising technique capable of providing morphological and functional information about atheromatous plaques. MRI using iron oxide particles, called ultrasmall superparamagnetic iron oxide (USPIO) particles, allows detection of macrophages in atherosclerotic tissue. Ferumoxytol has emerged as a new USPIO agent, which has an excellent safety profile. Based on the macrophage-selective properties of ferumoxytol, there is increasing number of recent reports suggesting its effectiveness to detect pathological inflammation. USPIO particles allow magnetic resonance detection of macrophages in atherosclerotic tissue. Ferumoxytol has emerged as a new USPIO agent, with an excellent safety profile. This has the potential to be used for MRI of the pathobiology of atherosclerosis.

Bilateral basal ganglia calcifications visualised on CT scan.

OpenAIRE

Brannan, T S; Burger, A A; Chaudhary, M Y

1980-01-01

Thirty-eight cases of basal ganglia calcification imaged on computed axial tomography were reviewed. Most cases were felt to represent senescent calcification. The possibility of a vascular aetiology in this group is discussed. A less common group of patients was identified with calcification secondary to abnormalities in calcium metabolism or radiation therapy. Three cases of basal ganglia calcifications were detected in juvenile epileptic patients receiving chronic anticonvulsants. These ca...

Effects of Ramadan Fasting on the Regulation of Inflammation

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Safieh Ebrahimi

2016-03-01

Full Text Available The month of Ramadan, as a model of intermittent fasting, is a valuable opportunity to investigate the effects of dietary modifications on human metabolism. Fasting improves insulin sensitivity, reduces atherogenic risk, oxidative stress, and inflammation. Inflammation plays a key role in the pathogenesis of different disorders including atherosclerosis, metabolic syndrome and cardiovascular diseases. Ramadan fasting can positively modulate cardiovascular risks and improves the metabolic syndrome features through suppression of inflammatory responses. In this review we attempt to present recent studies that addressed the regulatory role(s of this nutritional status on inflammation in patients with inflammatory diseases. These studies suggest that the anti-inflammatory effect of fasting is significant and could be considered as a complementary therapeutic approach in treatment of inflammatory disorders in patients.Keywords: Ramadan fasting, Inflammation, Metabolic syndrome, Cardiovascular diseaseAbstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract Abstract

Adipocyte induced arterial calcification is prevented with sodium thiosulfate

Energy Technology Data Exchange (ETDEWEB)

Chen, Neal X., E-mail: xuechen@iupui.edu [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); O’Neill, Kalisha; Akl, Nader Kassis [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); Moe, Sharon M. [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); Roudebush VA Medical Center, Indianapolis, IN (United States)

2014-06-20

Highlights: • High phosphorus can induce calcification of adipocytes, even when fully differentiated. • Adipocytes can induce vascular calcification in an autocrine manner. • Sodium thiosulfate inhibits adipocyte calcification. - Abstract: Background: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. Methods: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. Results: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. Conclusion: High phosphorus induced calcification of mature adipocytes, and

Vaccination against atherosclerosis

NARCIS (Netherlands)

Es, Thomas van

2009-01-01

Atherosclerosis, the predominantly underlying pathology of cardiovascular events, is the consequence of lipid deposition in the arterial wall, mostly as consequence of high levels of serum cholesterol. Treatment of atherosclerosis is mainly focused at the reduction of cholesterol levels by lipid

The roentgenographic study of placental calcifications in Korean pregnant

International Nuclear Information System (INIS)

Cho, Chung Che

1980-01-01

Calcifications in the placenta have been considered as a sign of the maturity because it is found frequently in variable degrees in full-term placentas. The placentas studied were those from deliveries at Chung-Ang University Hospital during the period of January 1978 to June 1980 and were excluded if their deliveries were by Caesarean section. Roentgenographic studies of placenta were performed postnatally in 135 cases delivered from normal pregnant. The results were as follows: 1. The incidence of calcification in the placenta was 53.3%. 2. The tendency of placenta calcification was increased as progress of maturity but not indicated as postmaturity. 3. Calcifications were less correlated with increasing gravidity or maternal age. 4. Calcifications occurred more frequently with increasing birth weight. 5. Calcifications in placentas were more frequently in the neonates with 10 scores of Apgar and normal level of maternal hemoglobin. 6. No significant correlation between incidence of calcification and maternal toxemia was observed. In the pregnant with an episode of previous abortion or S. P. R. M., incidence of calcification was apparently increased but statistically not significant. On the whole, placental calcifications are not harmful and identified as normal or proper aging process

The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/- mice.

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Peter M Mihailovic

Full Text Available Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/- mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/- mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/- with different doses of the shortened peptide (Cramp resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs, whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/- mouse model.

Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide

DEFF Research Database (Denmark)

Christophersen, Daniel Vest; Jacobsen, Nicklas Raun; Jensen, Ditte Marie

2016-01-01

Inflammation and oxidative stress are considered the main drivers of vasomotor dysfunction and progression of atherosclerosis after inhalation of particulate matter. In addition, new studies have shown that particle exposure can induce the level of bioactive mediators in serum, driving vascular.......5% plasma extracted from CB-exposed ApoE-/- mice caused vasoconstriction in aorta rings isolated from naive mice; this effect was abolished by the treatment with the serotonin receptor antagonist Ketanserin. In conclusion, repeated pulmonary exposure to nanosized CB and LPS caused lung inflammation without...

MR imaging of intracranial calcification; experimental and clinical studies

Energy Technology Data Exchange (ETDEWEB)

Yoon, Jong Hoon; Kim, Byung Jin; Kim, Yun Hyeon; Seo, Jeong Jin; Kang, Heoung Keun; Yang, Sung Yeul [Chonnam University Medical School, Kwangju (Korea, Republic of)

1995-05-15

This study was performed to evaluate MR signal intensity (SI) of calcification and to assess the capability of MRI in detection of various intracranial calcifications. The MR findings and ROI value of experimental model of calcium carbonate suspension according to each concentration (20, 35, 50%) and diameter (1-10 mm) and hydroxyapatite suspension according to each concentration (10, 20, 30, 40, 50%) were analyzed. A specimen of calcification in craniopharyngioma was analyzed for its composition by XRD (X-ray diffractometer) and ICP (inductively coupled plasma) methods. MRI of 34 patients with intracranial calcifications were retrospectively analyzed for signal intensity of the calcification and its capability to detect calcifications according to size, location, and contrast with adjacent lesion. The calcium carbonate phantom with larger diameter and low concentration showed lower signal intensity on T2 than T1WI. Hydroxyapatite phantom showed high signal intensity in 10-30% concentration and low signal intensity in 40-50% concentration on T1 weighted image. The 5 cases of 34 intracranial calcifications showed high signal intensity on T1 weighted image. The capability of MRI in the detection of intracranial calcifications decreased in the circumstances such as small size (< 2.5 mm) and intraventricular location. Although the size of calcification was small, the detection was easy in the good contrast with adjacent lesion. However, the detection of the small sized calcification was easy if the contrast with adjacent lesion was good. Intracranial calcification shows generally low signal intensity on T1 and T2 weighted image with the exception of occasional high SI on T1WI. Detection of intracranial calcification in MRI is affected by its composition, size, location, and contrast with adjacent lesion.

Atypical calcific tendinitis with cortical erosions

International Nuclear Information System (INIS)

Kraemer, E.J.; El-Khoury, G.Y.

2000-01-01

Objective. To present and discuss six cases of calcific tendinitis in atypical locations (one at the insertion of the pectoralis major and five at the insertion of the gluteus maximus).Patients and results. All cases were associated with cortical erosions, and five had soft tissue calcifications. The initial presentation was confusing and the patients were suspected of having infection or neoplastic disease.Conclusion. Calcific tendinitis is a self-limiting condition. It is important to recognize the imaging features of this condition to avoid unnecessary investigation and surgery. (orig.)

MRI of the basal ganglia calcification

International Nuclear Information System (INIS)

Maeda, Masayuki; Murata, Tetsuhito; Kimura, Hirohiko

1992-01-01

MR imaging was performed for 11 patients (9 in Down's syndrome and 2 in idiopathic intracerebral calcification) who showed calcifications in bilateral basal ganglia on CT. High signal intensity in the basal ganglia was found only in one patient with idiopathic intracerebral calcification on T1-weighted image. The calcified areas of all patients in Down's syndrome did not show high signal intensity on T1-weighted image. The exact reasons why MRI exhibits the different signal intensities in calcified tissue on T1-weighted image are unknown. Further clinical investigations will be needed. (author)

Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

DEFF Research Database (Denmark)

Bartels, E D; Bang, C A; Nielsen, L B

2009-01-01

and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early......BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development...

Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans

Science.gov (United States)

Goya, Luis; Martín, María Ángeles; Sarriá, Beatriz; Ramos, Sonia; Mateos, Raquel; Bravo, Laura

2016-01-01

Chronic inflammation has been identified as a necessary step to mediate atherosclerosis and cardiovascular disease and as a relevant stage in the onset and progression of several types of cancer. Considerable attention has recently been focused on the identification of dietary bioactive compounds with anti-inflammatory activities as an alternative natural source for prevention of inflammation-associated diseases. The remarkable capacity of cocoa flavanols as antioxidants, as well as to modulate signaling pathways involved in cellular processes, such as inflammation, metabolism and proliferation, has encouraged research on this type of polyphenols as useful bioactive compounds for nutritional prevention of cardiovascular disease and cancer. Data from numerous studies suggest that cocoa and cocoa-derived flavanols can effectively modify the inflammatory process, and thus potentially provide a benefit to individuals with elevated risk factors for atherosclerosis/cardiovascular pathology and cancer. The present overview will focus on the most recent findings about the effects of cocoa, its main constituents and cocoa derivatives on selected biomarkers of the inflammatory process in cell culture, animal models and human cohorts. PMID:27070643

Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans.

Science.gov (United States)

Goya, Luis; Martín, María Ángeles; Sarriá, Beatriz; Ramos, Sonia; Mateos, Raquel; Bravo, Laura

2016-04-09

Chronic inflammation has been identified as a necessary step to mediate atherosclerosis and cardiovascular disease and as a relevant stage in the onset and progression of several types of cancer. Considerable attention has recently been focused on the identification of dietary bioactive compounds with anti-inflammatory activities as an alternative natural source for prevention of inflammation-associated diseases. The remarkable capacity of cocoa flavanols as antioxidants, as well as to modulate signaling pathways involved in cellular processes, such as inflammation, metabolism and proliferation, has encouraged research on this type of polyphenols as useful bioactive compounds for nutritional prevention of cardiovascular disease and cancer. Data from numerous studies suggest that cocoa and cocoa-derived flavanols can effectively modify the inflammatory process, and thus potentially provide a benefit to individuals with elevated risk factors for atherosclerosis/cardiovascular pathology and cancer. The present overview will focus on the most recent findings about the effects of cocoa, its main constituents and cocoa derivatives on selected biomarkers of the inflammatory process in cell culture, animal models and human cohorts.

Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans

Directory of Open Access Journals (Sweden)

Luis Goya

2016-04-01

Full Text Available Chronic inflammation has been identified as a necessary step to mediate atherosclerosis and cardiovascular disease and as a relevant stage in the onset and progression of several types of cancer. Considerable attention has recently been focused on the identification of dietary bioactive compounds with anti-inflammatory activities as an alternative natural source for prevention of inflammation-associated diseases. The remarkable capacity of cocoa flavanols as antioxidants, as well as to modulate signaling pathways involved in cellular processes, such as inflammation, metabolism and proliferation, has encouraged research on this type of polyphenols as useful bioactive compounds for nutritional prevention of cardiovascular disease and cancer. Data from numerous studies suggest that cocoa and cocoa-derived flavanols can effectively modify the inflammatory process, and thus potentially provide a benefit to individuals with elevated risk factors for atherosclerosis/cardiovascular pathology and cancer. The present overview will focus on the most recent findings about the effects of cocoa, its main constituents and cocoa derivatives on selected biomarkers of the inflammatory process in cell culture, animal models and human cohorts.

Prevalence of breast arterial calcification in hypertensive patients

International Nuclear Information System (INIS)

Cetin, M.; Cetin, R.; Tamer, N.

2004-01-01

AIM: To determine the age-specific prevalence of breast arterial calcifications in patients with systemic hypertension. METHODS: The mammograms and patient records of 2406 women who underwent screening or diagnostic mammography were reviewed retrospectively. Mammograms were evaluated for the presence of arterial calcification and results were coded. Hypertension was defined as use of anti-hypertensive agents and diabetes was defined as use of oral hypoglycaemic agents or insulin. RESULTS: The prevalence of breast arterial calcification among hypertensives (17.6%) was lower than among diabetics (25.4%). The prevalence in the non-diabetic, non-hypertensive group was lowest (7.3%). The prevalence increased with age in all three groups. The highest prevalence was found in diabetics older than 60 years (81.8%). Breast arterial calcification was not found among women younger than 40 years. CONCLUSION: Breast arterial calcification is associated with hypertension and prevalence increases with age. Breast arterial calcification on mammograms may indicate unsuspected hypertension especially in non-diabetic patients

Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

Energy Technology Data Exchange (ETDEWEB)

Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

2003-09-01

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

Intranasal delivery of E-selectin reduces atherosclerosis in ApoE-/- mice.

Directory of Open Access Journals (Sweden)

Xinhui Li

Full Text Available Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to (pre-tolerization or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.

The effect of social environment on markers of vascular oxidative stress and inflammation in the Watanabe heritable hyperlipidemic rabbit.

Science.gov (United States)

Nation, Daniel A; Gonzales, Julie A; Mendez, Armando J; Zaias, Julia; Szeto, Angela; Brooks, Larry G; Paredes, Jamespaul; D'Angola, Alyssa; Schneiderman, Neil; McCabe, Philip M

2008-04-01

Previous research demonstrated that social environment can influence progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. This study examined the effect of social environment on markers of oxidative stress and inflammation to clarify the physiological pathways potentially responsible for the influence of social environment on disease. WHHL rabbits were assigned to 1 of 3 social groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily; and an individually-caged group. The stable group engaged in more affiliative social behavior than the unstable group. The unstable group showed more agonistic behavior compared with the stable group and higher C-reactive protein levels than the individually caged group. The individually caged group was behaviorally sedentary, had higher 24-hour urinary catecholamine levels than the other groups, and exhibited higher NAD(P)H-oxidase activity in the aortic arch relative to the stable group. The results suggest that social environment creates distinct behavioral contexts that can affect markers of inflammation and oxidative stress early in the development of atherosclerosis. Specifically, physical inactivity associated with individual caging affects indices of oxidative stress and inflammation. These pathophysiological markers may help to explain behaviorally related differences in the extent of atherosclerosis observed in prior studies.

Medial arterial calcification in diabetes and its relationship to neuropathy

DEFF Research Database (Denmark)

Jeffcoate, W J; Rasmussen, Lars Melholt; Hofbauer, L C

2009-01-01

Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular and all-cause mortality. The term calcification......, such as calcitonin gene-related peptide, which are inherently protective. The association between distal symmetrical neuropathy and calcification of the arterial wall highlights the fact that neuropathy may be an independent risk factor for cardiovascular mortality.......Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular and all-cause mortality. The term calcification...

Anti-Inflammatory effect of Buddleja officinalis on vascular inflammation in human umbilical vein endothelial cells.

Science.gov (United States)

Lee, Yun Jung; Moon, Mi Kyoung; Hwang, Sun Mi; Yoon, Jung Joo; Lee, So Min; Seo, Kwan Soo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2010-01-01

Vascular inflammation process has been suggested to be an important risk factor in the initiation and development of atherosclerosis. In this study, we investigated whether and by what mechanisms an aqueous extract of Buddleja officinalis (ABO) inhibited the expressions of cellular adhesion molecules, which are relevant to inflammation and atherosclerosis. Pretreatment of human umbilical vein endothelial cells (HUVEC) with ABO (1-10 microg/ml) for 18 hours dose-dependently inhibited TNF-alpha-induced adhesion U937 monocytic cells, as well as mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1). Pretreatment with ABO also blocked TNF-alpha-induced ROS formation. Nuclear factor-kappa B (NF-kappaB) is required in the transcription of these adhesion molecule genes. Western blot analysis revealed that ABO inhibits the translocation of the p65 subunit of NF-kappaB to the nucleus. ABO inhibited the TNF-alpha-induced degradation of IkappaB-alpha, an inhibitor of NF-kappaB, by inhibiting the phosphorylation of IkappaB-alpha in HUVEC. Taken together, ABO could reduce cytokine-induced endothelial adhesiveness throughout down-regulating intracellular ROS production, NF-kappaB, and adhesion molecule expression in HUVEC, suggesting that the natural herb Buddleja officinalis may have potential implications in atherosclerosis.

Evaluation of pineal calcification in children

International Nuclear Information System (INIS)

Ando, Kazuo; Odagiri, Kunio; Fujiwara, Takuya; Tanohata, Kazunori; Matsui, Kengo; Okano, Shigeki.

1987-01-01

The study cases were 804 patients who had received either CT or plain radiographs for some reasons. Their ages ranged from newborn to 15 years old. Twenty four patients had the pineal calcification, in which one patient had the pineal region tumor and 4 patients had precocious puberty. The incidence of the pineal calcification was observed on CT as 0.2, 5.8, and 14 % in their age of 0 to 5, 6 to 10, and 11 to 15 years old, respectively. On the other hand, this finding was detected only in 0, 1.1, and 1.2 % on plain radiographs. In conclusion, pineal calcification on CT may suggest the pathological state in children. Although it is observed in a minority of normal children, such a calcification could be looked upon as not only pineal region tumor but precocious puberty and other intracranial disorders with suspicion. (author)

The relationship of socioeconomic status with coronary artery calcification and pericardial fat.

Science.gov (United States)

Nafakhi, Hussein; Almosawi, Abdulameer; Alnafakh, Hasan; Mousa, Widad

2017-01-01

Little data currently exist supporting the correlation of socioeconomic status (SES) to markers of subclinical coronary atherosclerosis. The main aim was to investigate the relationship of SES measured by economic status and educational level with coronary artery calcification (CAC) and pericardial fat volume (PFV) assessed by multi-detector computed tomography (MDCT). A total of 220 consecutive patients with suspected coronary artery disease, who underwent 64-slice MDCT angiography for assessment of coronary atherosclerosis, were recruited between January 2014 and March 2015. Of these, 186 patients were enrolled in this cross sectional study. Low economic status patients showed higher PFV values; median (inter-quartile range [IQR] was 94 [50-140] cm3, p = 0.00001 and r = 0.37, compared to patients with high economic status, and this association persisted even after multiple logistic regression to conventional cardiac risk factors (p = 0.004, CI 7.3-30.4), while patients with low economic status reported a higher calcium score (but statistically non significant) (p = 0.12) compared to high economic status patients. Pa-tients with no formal education showed higher PFV (median [IQR] was 93 [48-140] cm3, p = 0.01) compared to patients with bachelor's degree (median [IQR] was 56 [28-92] cm3), but this association was attenuated after further adjustment for conventional cardiac risk factors (p = 0.1, CI -9.52-10.88), while CAC showed no significant correlation with educational level (p = 0.2, r = 0.117). Socioeconomic status, particularly economic status measure, reported a significant inverse relationship with PFV independent of conventional cardiac risk factors.

Obstructive sleep apnea and inflammation.

LENUS (Irish Health Repository)

McNicholas, Walter T

2012-02-01

The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.

The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

Directory of Open Access Journals (Sweden)

Dimitar Divchev

2008-06-01

Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

A Novel Method for Determining Calcification Composition

National Research Council Canada - National Science Library

Maidment, Andrew D

2005-01-01

Breast calcifications can be divided into two broad categories. Type I are composed of calcium oxylate while type II calcifications all have some phosphorus content most typically calcium hydroxyapatite...

Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification.

Science.gov (United States)

Zaid, Maryam; Miura, Katsuyuki; Fujiyoshi, Akira; Abbott, Robert D; Hisamatsu, Takashi; Kadota, Aya; Arima, Hisatomi; Kadowaki, Sayaka; Torii, Sayuki; Miyagawa, Naoko; Suzuki, Sentaro; Takashima, Naoyuki; Ohkubo, Takayoshi; Sekikawa, Akira; Maegawa, Hiroshi; Horie, Minoru; Nakamura, Yasuyuki; Okamura, Tomonori; Ueshima, Hirotsugu

2016-01-01

Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C). Whether LDL-P is associated with subclinical atherosclerosis, independent of LDL-C, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis. We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined. LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made. In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

High-grade histologic features of DCIS are associated with R5 rather than R3 calcifications in breast screening mammography.

LENUS (Irish Health Repository)

Hayes, Brian D

2013-01-01

Mammographic calcification is an important radiologic feature of early breast carcinoma whose index of suspicion for malignancy may be reported by a five-tier R-category system. This study aims to describe the histologic diagnoses underlying screen-detected mammographic calcifications using both digital and screen-film mammography, and to correlate these findings with radiologic R-categories. Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2011 were identified, who underwent needle-core biopsy for assessment of mammographic calcifications without associated mass or architectural distortion. Radiologic R-category was correlated with biopsy and excision histology reports. A total of 776 cases of calcification were identified, involving 769 individual patients. The radiologic R-categories were as follows: R3 513 (66.1%), R4 192 (24.7%), R5 71 (9.1%). The positive predictive values for malignancy were R3 32.6%, R4 69.8%, R5 95.8%. Several histologic features of DCIS were associated with R5 rather than R3 radiology: high nuclear grade, solid or cribriform architecture, necrosis, periductal inflammation or fibrosis, and associated microinvasive or invasive carcinoma. Mammographic lesions and histologic whole and invasive tumors increased in size from R3 to R5. Radiologic size of calcifications correlated with whole (but not invasive) tumor size, although it tended to underestimate it by several millimeters. Digital-detected calcifications were more likely than screen-film detected to be categorized as R3 and less likely R4 or R5, and there was no significant difference in positive predictive value between the two imaging techniques in any R-category. In conclusion, histologic features of DCIS, in particular those associated with high grade, are associated with R5 radiology. There is no significant difference in positive predictive value for malignancy in any R-category between digital and screen-film mammography.

Computed tomography of calcification of the basal ganglia

International Nuclear Information System (INIS)

Park, Churl Min; Suh, Soo Jhi; Kim, Soon Yong

1981-01-01

Calcifications of the basal ganglia are rarely found at routine autopsies and in skull radiographs. CT is superior to the plain skull radiographs in detecting intracranial attenuation differences and may be stated to be the method of choice in the diagnosis of intracranial calcifications. Of 5985 brain CT scans performed in Kyung Hee University Hospital during past 3 years, 36 cases were found to have high attenuation lesions suggesting calcifications within basal ganglia. 1. The incidence of basal ganglia calcification on CT scan was about 0.6%. 2. Of these 36 cases, 34 cases were bilateral and the remainder was unilateral. 3. The plain skull films of 23 cases showed visible calcification of basal ganglia in 3 cases (13%). 4. No specific metabolic disease was noted in the cases

Additive effects of lupin protein and phytic acid on aortic calcification in ApoE deficient mice.

Science.gov (United States)

Schutkowski, Alexandra; Hirche, Frank; Geissler, Stefanie; Radtke, Juliane; Stangl, Gabriele I

2015-03-01

Lupin proteins have repeatedly been shown to exhibit lipid lowering properties and reduce aortic calcification in atherosclerosis models. Despite many efforts on its identification, the component which is responsible for the observed effects is still under debate. Phytic acid which is generally associated with lupin protein isolates has currently been described as bioactive plant compound. The objective of the study was to determine the role of associated phytic acid for the described lupin protein effects. A two-factorial study with ApoE knockout mice was conducted in which mice received lupin protein isolate or casein with or without phytase. Phytic acid was added to the casein diets to a final concentration identical to the lupin protein diets. Here we show that the serum concentrations of cholesterol, lathosterol and desmosterol were lower and the faecal bile acid excretion was higher in the groups fed lupin proteins than in the groups fed casein ( p  < 0.05). Mice that received the lupin protein diet containing phytic acid were characterized by a lower aortic calcification than mice of the other three groups ( p  < 0.05). In conclusion, our results show that the cholesterol lowering properties of lupin protein isolate were not caused by phytic acid. However, the hypocalcific action of lupin proteins appears to depend on the combination of lupin proteins and phytic acid.

Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis.

Science.gov (United States)

Willenberg, T; Diehm, N; Zwahlen, M; Kalka, C; Do, D-D; Gretener, S; Ortmann, J; Baumgartner, I

2010-04-01

Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

[Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].

Science.gov (United States)

Alboni, Paolo; Alboni, Marco

2006-11-01

Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been

Co-crystallization of cholesterol and calcium phosphate as related to atherosclerosis

Science.gov (United States)

Hirsch, Danielle; Azoury, Reuven; Sarig, Sara

1990-09-01

Calcification of atherosclerotic plaques occurs very frequently and aggravates the disease. In biological systems, epitaxial relationships between crystal structures may be important in nucleating the deposit of a solid phase. The biologically preferred calcium phosphate species, apatite, and cholesterol crystal have structurally compatible crystallographic faces which allow epitaxial growth of one crystal upon another. The present study describes a new approach to explore, in vitro, the crystallization processes of calcium phosphate (CaP) with cholesterol (CS) and cholestanol (CN) which are related to atherosclerosis. Aqueous solutions containing calcium and phosphate ions or CaP crystals as hydroxyapatite were added into saturated ethanolic solutions of CS or CS and 10% CN. After precipitation, crystals were collected and analyzed by nuclear magnetic resonance (NMR), infra-red (IR), X-ray, scanning electron microscope (SEM-LINK), differential scanning calorimeter (DSC) and atomic absorption. The principal result is the well-formed crystals precipitation when an aqueous solution and CaP seed crystals were added to saturated solutions of CS and 10% CN. Cholesterol-cholestanol dihydrate (CC2W) crystals precipitated in the presence of CaP seeds were compared to the CC2W crystals obtained without the mineral compound. The results of this comparison indicate a special link between crystals of CaP and CC2W, and support the epitaxial relationship between the two kinds of crystals. The potential of CC2W crystals to be precipitated by CaP seed crystals prove likewise the possible significant role of the cholestanol metabolite in the process of cholesterol crystallization and calcification in the arteries.

Radiological observation of determination of sex by costal cartilage calcification

International Nuclear Information System (INIS)

Kang, Shin Hwa; Won, Jong Jin; Rhee, Song Joo; Moon, Moo Chang; Oh, Jong Hyun; Choi, Ki Chul

1979-01-01

The difference of patterns of costal cartilage calcification in male and female had been first described by Fischer in 1955. Thereafter several reports were published, but specific clinical significance was not found. During the period from January, 1978 to December, 1978, we, in the Department of Radiology, Jeonbug National University, studied 2164 cases that showed the entire 12 pairs of ribs. Among these we detected 1494 cases of costal cartilage calcification and frequent sites of calcification. Patterns of costal cartilage calcification were classified into six groups- type l: central, type II: marginal, type III: junctional type, type IV: railroad, type V: diffuse, type VI: mixed. Results are as follows; 1. In a total of 2164 cases, calcification of costal cartilage was present in 1494 cases(69.0%). Of 1181 males 780 cases(66.0%) showed calcification, and of 983 females 714 cases (72.6%) showed calcification. 2. In 439 cases of males, except for 341 cases that showed calcification within the first costal cartilage, patterns of costal cartilage calcification were as follows: marginal type in 265 cases (60.4%), junctional type in 134 cases (30.5%), mixed type in 21 cases (0.5%), central type in 17 cases(3.8%), and railroad type in 2 cases (0.5%). Diffuse type was not present. 3. In 492 cases of females, except of 222 cases that showed calcification within the first costal cartilage, patterns of costal cartilage calcification were as follows; central type in 336 cases (68.3%), junctional type in 94 cases(19.1%), mixed type in 24 cases (4.9%), railroad type in 19 cases (3.9%), and diffuse type in 14 cases (2.8%). 4. When central calcification was observed, predictive value to female was 94.7%. When marginal calcification was observed, predictive value to male was 987.4%. 5. Males frequently showed calcification in upper costal cartilages, and females in lower costal cartilages.

PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.

Science.gov (United States)

Baron, Morgane; Leroyer, Aurélie S; Majd, Zouher; Lalloyer, Fanny; Vallez, Emmanuelle; Bantubungi, Kadiombo; Chinetti-Gbaguidi, Giulia; Delerive, Philippe; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

2011-09-01

Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse. (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations. ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry. An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver. Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Prevalence of carotid and pulp calcifications: a correlation using digital panoramic radiographs

International Nuclear Information System (INIS)

Clark, Stephen J.; Scheetz, James P.; Khan, Zafrulla; Farman, Allan G.; Horsley, Scott H.; Beckstrom, Brice

2009-01-01

To compare the prevalence of pulp calcification with that of carotid calcification using digital panoramic dental radiographs. Digital panoramic radiographs of patients at a dental oncology clinic were included if (1) the carotid artery bifurcation region was visible bilaterally and (2) the patient had non-restored or minimally restored molars and/or canines. An endodontist evaluated the images for pulpal calcifications in the selected teeth. An oral and maxillofacial radiologist independently evaluated the same images for calcifications in the carotid bifurcation region. Odds-ratio and Pearson χ 2 were used for data analysis. Presence of pulpal calcification was also evaluated as a screening test for the presence of carotid calcification. A total of 247 panoramic radiographs were evaluated. 32% (n=80) had pulpal calcifications and 25% (n=61) had carotid calcifications with 12% (n=29) having both carotid and pulp calcifications. A significantly higher prevalence of both pulp and carotid calcification was found in subjects older than age 60 years compared to younger age groups. Accuracy of pulpal calcification in screening for carotid calcification was 66.4%. Both pulp and carotid calcifications were more prevalent in older individuals. The presence of pulp calcification was not a strong predictor for the presence of carotid calcification. (orig.)

Prevalence of carotid and pulp calcifications: a correlation using digital panoramic radiographs

Energy Technology Data Exchange (ETDEWEB)

Clark, Stephen J. [School of Dentistry, University of Louisville, Department of Periodontics, Endodontics and Dental Hygiene, Louisville, KY (United States); Scheetz, James P.; Khan, Zafrulla [University of Louisville, Department of Diagnostic Sciences, Prosthodontics and Restorative Dentistry, School of Dentistry, Louisville, KY (United States); Farman, Allan G. [School of Dentistry, University of Louisville, Department of Periodontics, Endodontics and Dental Hygiene, Louisville, KY (United States); Horsley, Scott H.; Beckstrom, Brice

2009-03-15

To compare the prevalence of pulp calcification with that of carotid calcification using digital panoramic dental radiographs. Digital panoramic radiographs of patients at a dental oncology clinic were included if (1) the carotid artery bifurcation region was visible bilaterally and (2) the patient had non-restored or minimally restored molars and/or canines. An endodontist evaluated the images for pulpal calcifications in the selected teeth. An oral and maxillofacial radiologist independently evaluated the same images for calcifications in the carotid bifurcation region. Odds-ratio and Pearson {chi}{sup 2} were used for data analysis. Presence of pulpal calcification was also evaluated as a screening test for the presence of carotid calcification. A total of 247 panoramic radiographs were evaluated. 32% (n=80) had pulpal calcifications and 25% (n=61) had carotid calcifications with 12% (n=29) having both carotid and pulp calcifications. A significantly higher prevalence of both pulp and carotid calcification was found in subjects older than age 60 years compared to younger age groups. Accuracy of pulpal calcification in screening for carotid calcification was 66.4%. Both pulp and carotid calcifications were more prevalent in older individuals. The presence of pulp calcification was not a strong predictor for the presence of carotid calcification. (orig.)

Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan

International Nuclear Information System (INIS)

Hsieh, Y.-C.; Hsieh, F.-I; Lien, L.-M.; Chou, Y.-L.; Chiou, H.-Y.; Chen, C.-J.

2008-01-01

Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) ≥ 1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with ε4 allele of APOE than those without ε4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level > 10 μg/L or had arsenic exposure > 0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1

Breast arterial calcifications are correlated with subsequent development of coronary artery calcifications, but their aetiology is predominantly different

Energy Technology Data Exchange (ETDEWEB)

Maas, Angela H.E.M. [Department of Cardiology, Isala Klinieken, Groot Wezenland 20, 8011 JW Zwolle (Netherlands)], E-mail: a.maas@diagram-zwolle.nl; Schouw, Yvonne T. van der; Atsma, Femke [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht (Netherlands); Beijerinck, David; Deurenberg, Jan J.M. [Preventicon Breast Cancer Screening Center, Stationsplein 91, 3511ED Utrecht (Netherlands); Mali, Willem P.Th.M. [Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht (Netherlands); Graaf, Y. van der [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht (Netherlands)

2007-09-15

Objective: To study whether calcifications in breast arteries, as seen on mammograms, predict future development of coronary artery calcifications. Methods: We studied 499 women, aged 49-70 years, participating in a breast cancer screening program and investigated whether arterial calcifications in the breast (BAC) are associated with coronary arterial calcifications (CAC) after 9 years follow-up. Mammograms were reviewed for the presence of BAC. CAC was assessed by multi slice computed tomography (MSCT). With logistic regression analysis the independent effect of various risk factors on BAC and CAC was measured. Results: BAC was present in 58 of 499 women (12%) and CAC score > 0 was present in 262 of 499 women (53%). BAC was strongly associated with CAC (OR 3.2, 95% CI 1.71-6.04) and this remained significant after adjustment for age at baseline and the duration of follow-up (OR 2.1, 95% CI 1.10-4.23). Most CV risk factors were associated with CAC but not with BAC. Only parity was significantly associated with both increased CAC (OR 2.1, 95% CI 1.21-3.60) and increased BAC (OR 5.3, 95% CI 1.23-22.43). Breastfeeding was associated with BAC (OR 3.4, 95% CI 1.40-8.23) but not with CAC (OR 1.3, 95% CI 0.84-1.93). Conclusion: Breast arterial calcifications are predictive of subsequent development of calcifications in the coronary arteries.

Impact of Hydroxychloroquine on Atherosclerosis and Vascular Stiffness in the Presence of Chronic Kidney Disease.

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Ashutosh M Shukla

Full Text Available Cardiovascular disease is the largest cause of morbidity and mortality among patients with chronic kidney disease (CKD and end-stage kidney disease, with nearly half of all deaths attributed to cardiovascular disease. Hydroxychloroquine (HCQ, an anti-inflammatory drug, has been shown to have multiple pleiotropic actions relevant to atherosclerosis. We conducted a proof-of-efficacy study to evaluate the effects of hydroxychloroquine in an animal model of atherosclerosis in ApoE knockout mice with and without chronic kidney disease. Forty male, 6-week-old mice were divided into four groups in a 2 x 2 design: sham placebo group; sham treatment group; CKD placebo group; and CKD treatment group. CKD was induced by a two-step surgical procedure. All mice received a high-fat diet through the study duration and were sacrificed after 16 weeks of therapy. Mice were monitored with ante-mortem ultrasonic echography (AUE for atherosclerosis and vascular stiffness and with post-mortem histology studies for atherosclerosis. Therapy with HCQ significantly reduced the severity of atherosclerosis in CKD mice and sham treated mice. HCQ reduced the area of aortic atherosclerosis on en face examination by approximately 60% in HCQ treated groups compared to the non-treated groups. Additionally, therapy with HCQ resulted in significant reduction in vascular endothelial dysfunction with improvement in vascular elasticity and flow patterns and better-preserved vascular wall thickness across multiple vascular beds. More importantly, we found that presence of CKD had no mitigating effect on HCQ's anti-atherosclerotic and vasculoprotective effects. These beneficial effects were not due to any significant effect of HCQ on inflammation, renal function, or lipid profile at the end of 16 weeks of therapy. This study, which demonstrates structural and functional protection against atherosclerosis by HCQ, provides a rationale to evaluate its use in CKD patients. Further studies

A Waving Horn on the Big Mitral Annulus Calcification: Caseous Calcification of the Mitral Annulus with Abscess Formation

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Li-Tan Yang

2014-06-01

Full Text Available Caseous calcification of the mitral annulus (CCMA is a rare variant of mitral annular calcification. It comprises a combination of calcium, fatty acids, and cholesterol, and is characterized by heterogeneity in echocardiographic images, with peripheral areas of calcification surrounding a central area of echolucency, resembling a periannular mass. Here, we describe a case of CCMA combined with a mitral annulus abscess, manifesting as a waving, horn-like structure. Although the image characteristics of the posterior mitral annulus suggested CCMA, additional findings warranted further work-up and studies.

Tortuosity and calcification of the splenic artery. More than an additional finding; Schlaengelung und Verkalkung der Milzarterie im Roentgenbild. Mehr als ein Nebenbefund

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Golder, W.A. [SELARL Association d' Imagerie Medicale, Troyes (France)

2008-11-15

Tortuosity of the splenic artery and calcification of the vessel wall are typical additional findings on plain abdominal x-ray. The combination of both anomalies is common in elderly persons presenting without symptoms of splenic ischemia. Its pathogenesis is thought to be multifactorial. In infancy and childhood, the splenic artery is stretched in its entire course. A growing difference between the length of the vessel and the distance between its origin and the splenic hilum gives rise to tortuosity. The artery's proximal segment is involved more frequently and more severely than the distal one. The tortuous route of the vessel is accentuated by the direction of its major branches, which is roughly perpendicular to the main trajectory. Neither tortuosity nor calcification should be taken to be risk factors for the comparatively common splenic artery aneurysm. Calcific deposits are not confined to the media but are also detected in the intima of the vascular wall. Critical narrowings of the lumen arising on the calcium deposits are not observed. Calcifying atherosclerosis of the splenic artery is comparable to medial sclerosis of the peripheral arteries frequently noticed in diabetics and dialysis patients. Only the less important calcification of the intima may be attributed to mechanisms of the hydrohemodynamic theory of atherosclerosis. The spleen's blood storage capacity may contribute to the characteristic age-dependent alterations of the shape and course of the splenic artery. (orig.) [German] Die Schlaengelung der Milzarterie und Verkalkungen in der Wand des Gefaesses sind ein typischer Nebenbefund bei der Roentgenuntersuchung des Abdomens. Die Kombination wird v. a. bei Senioren beobachtet, ohne dass Symptome einer Mangelperfusion der Milz fassbar sind. Bei der Pathogenese wirken eine Reihe verschiedener Faktoren zusammen. Im Kindesalter verlaeuft die A. lienalis stets gestreckt. Die zunehmende Schlaengelung wird durch die wachsende Differenz

Infrapopliteal calcification patterns in critical limb ischemia: diagnostic, pathologic and therapeutic implications in the search for the endovascular holy grail.

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Mustapha, Jihad A; Diaz-Sandoval, Larry J; Saab, Fadi

2017-06-01

Critical limb ischemia (CLI) represents the terminal stage of peripheral arterial disease (PAD) and is characterized by multilevel and multivessel disease. Amongst patients with infrainguinal disease, approximately one third have predominantly isolated infrapopliteal disease and the remaining two thirds, a combination of femoropopliteal and infrapopliteal disease. Isolated infrapopliteal disease is mainly seen in the elderly, diabetic, or dialysis-dependent patients. These patients have higher risk of amputation and shorter amputation-free survival. Infrapopliteal disease presents with either complex high-grade calcified tandem lesions in multiple vessels or with long chronic total occlusion (CTO) segments with plaques characterized by higher calcium and lower fibro-fatty content than the inflow vessels, as arterial calcium deposition increases as we progress distally in the arterial tree. Vascular calcification occurs in both intima and media. Intimal calcification leads to development of calcified atheroma and occlusive lesions. Medial calcification leads to stiffening and decrease in arterial wall elasticity and compliance leading to atherosclerosis, reduced perfusion, and PAD, increasing cardiovascular mortality among patients with end-stage renal disease. This article attempts to review the implications of the diverse pathologic patterns of calcium distribution in infrapopliteal vessels of CLI patients, on the diagnostic modalities, technological developments, and the evolution of therapeutic approaches to improve outcomes among these patients. A critical analysis of the currently available data is provided, pointing to the surprising omission on the role of calcium on outcomes, and future directions are discussed. Is infrapopliteal calcium a roadblock or the avenue towards new paths? Necessity remains the mother of invention.

Clinical significance of intramammary arterial calcifications in diabetic women

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Milošević Zorica

2004-01-01

Full Text Available Background. It is well known that intramammary arterial calcifications diagnosed by mammography as a part of generalized diabetic macroangiopathy may be an indirect sign of diabetes mellitus. Hence, the aim of this study was to determine the incidence of intramammary arterial calcifications, the patient’s age when the calcifications occur, as well as to observe the influence of diabetic polineuropathy, type, and the duration of diabetes on the onset of calcifications, in comparison with nondiabetic women. Methods. Mammographic findings of 113 diabetic female patients (21 with type 1 diabetes and 92 with type 2, as well as of 208 nondiabetic women (the control group were analyzed in the prospective study. The data about the type of diabetes, its duration, and polineuropathy were obtained using the questionnaire. Statistical differences were determined by Mann-Whitney test. Results. Intramammary arterial calcifications were identified in 33.3% of the women with type 1 diabetes, in 40.2% with type 2, and in 8.2% of the women from the control group, respectively. The differences comparing the women with type 1, as well as type 2 diabetes and the controls were statistically significant (p=0.0001. Women with intramammary arterial calcifications and type 1 diabetes were younger comparing to the control group (median age 52 years, comparing to 67 years of age, p=0.001, while there was no statistically significant difference in age between the women with calcifications and type 2 diabetes (61 years of age in relation to the control group (p=0.176. The incidence of polineuropathy in diabetic women was higher in the group with intramammary arterial calcifications (52.3% in comparison to the group without calcifications (26.1%, (p=0.005. The association between intramammary arterial calcifications and the duration of diabetes was not found. Conclusion. The obtained results supported the theory that intramammary arterial calcifications, detected by

Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

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Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2017-10-01

Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS

Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

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Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

2017-07-01

To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Sphingosine 1-Phosphate and Atherosclerosis

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Yatomi, Yutaka

2018-01-01

Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties. Recently, the mechanism for the biased distribution of S1P on HDL has been elucidated; apolipoprotein M (apoM) carries S1P on HDL. ApoM is also a modulator of S1P, and the metabolism of apoM-containing lipoproteins largely affects the plasma S1P level. Moreover, apoM modulates the biological properties of S1P. S1P bound to albumin exerts both beneficial and harmful effects in the pathogenesis of atherosclerosis, while S1P bound to apoM strengthens anti-atherosclerotic properties and might weaken the pro-atherosclerotic properties of S1P. Although the detailed mechanisms remain to be elucidated, apoM and S1P might be novel targets for the alleviation of atherosclerotic diseases in the future. PMID:28724841

Calcific retropharyngeal tendinitis

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Karasick, D.; Karasick, S.

1981-01-01

Calcific retropharyngeal tendinitis is an imflammation of the longus colli muscle tendon which is located on the anterior surface of the verterbral column extending from the atlas to the third thoracic vertebra. The acute inflammatory condition is selflimiting with symptoms consisting of a gradually increasing neck pain often associated with throat pain and difficulty swallowing. The pain is aggravated by head and neck movement. Clinically the condition can be confused with retropharyngeal absecess, meningitis, infectious spondylitis, and post-traumatic muscle spasm. The radiographic features of this condition consist of pre-vertebral soft tissue swelling from C1 to C4 and amorphous calcific density in the longus colli tendon anterior to the body of C2 and inferior to the anterior arch of C1. (orig.)

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications

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Jordi Bover

2016-11-01

Full Text Available Cardiovascular (CV calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD–MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc., we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.

Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

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Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

2014-01-01

It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

Anti-Inflammatory Effect of Red Piper Crocatum Leaves Extract Decrease TNF-α and IL-6 Levels in Wistar Rat with Atherosclerosis

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Sri Wahjuni

2016-05-01

Full Text Available Background: This research aims to find a cure for anti-inflammation, based on the utilization of red piper crocatum. The research was started with descriptive study to explore active components of red piper crocatum leaf and followed by experimental study to investigate red piper crocatum activity of the leaf extract in anti-inflammation induced Wistar rat. In this research observed three dominant components: caryophyllene bicyclo [5.2.0] none,2 methylene-4,8,8-trimethyl-4-vinyl; phytol; 5,9-propano-5H-benzocycloheptene,6,7,8,9-tetrahydro-7,11-bis(methylene; 4,4-ethynedioxy-2-hexadecen-15-15 olide 1,4,9-trioxaspiro [4,15] eic os-6-en-8-one, 10 methyl; 1H-1,2,4-triazole-5(H-thione,4-allyl-3-(3-furyl; Benzofuran,2,3-dihydro-2-methyl-7-phenyl which are possibly active to inhibit anti-inflammation to atherosclerosis. Bad eating habits also can cause various health problems, such as obesity, dyslipidemia, inflammation to atherosclerosis. This study was conducted to investigate of red piper crocatum leaves extract as an anti-inflammation through decrease of biochemistry markers TNF-α and IL-6 levels. Method: This is a true experimental with randomized pre-test and post-test control group design, using 50 Wistar rats that are divided into 5 groups: control group using 0 mg/kg BW red piper crocatum leaves extract, treatment group 1 using 50 mg/kg BW red piper crocatum leaves extract, treatment group 2 using 100 mg/kg BW red piper crocatum leaves extract, treatment group 3 using 150 mg/kg BW red piper crocatum leaves extract, and treatment group 4 200mg/kg BW red piper crocatum leaves extract. Results: It was observed that intake of 150 mg/BW red piper crocatum leaves extract results in the highest significance decrease of 45.63% of TNF-α levels from (28.62 ± 1.25 to 15.56 ± 7.20 рg/mL and a significance decrease of 15.42% of IL-6 level from (134.64 ± 1.98 to 113.87 ± 4.30 рg/mL. Conclusion: It can be concluded that intake of red piper crocatum

Calcifications of the bladder in schistosomiasis

International Nuclear Information System (INIS)

Wechmar, M. von; Vogel, H.

1989-01-01

In schistosomiasis calcification of the urinary bladder are characteristic signs that allow a corresponding diagnosis in endemic regions. Problems concerning differential diagnosis occur only in very rare cases. The calcifications of the bladder can be easily detected by native diagnostics. A late complication in an affected bladder is often a bladder carcinoma. (orig.) [de

The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type

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Tueysuez, Beyhan [Istanbul University, Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul (Turkey); Gazioglu, Nurperi [Istanbul University, Department of Neurosurgery, Cerrahpasa Medical School, Istanbul (Turkey); Uenguer, Savas [Istanbul University, Department of Pediatric Radiology, Cerrahpasa Medical School, Istanbul (Turkey); Aji, Dolly Yafet [Istanbul University, Department of Pediatrics, Cerrahpasa Medical School, Istanbul (Turkey); Tuerkmen, Seval [Istanbul University, Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul (Turkey); Universitatsklinikum Berlin, Charite Virchow-Klinik, Berlin (Germany)

2009-01-15

A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. (orig.)

The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type

International Nuclear Information System (INIS)

Tueysuez, Beyhan; Gazioglu, Nurperi; Uenguer, Savas; Aji, Dolly Yafet; Tuerkmen, Seval

2009-01-01

A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. (orig.)

The Relation between Calcium Supplement Consumption and Calcific Shoulder Tendonitis

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Alireza Rouhani

2015-10-01

Full Text Available Background: Calcific tendonitis is a common cause of non-traumatic shoulder pain. Previous studies have suggested a relation between minerals and endocrine and calcium deposition. Thus, hypercalcemia is probably related to calcific tendonitis. This study aims at evaluating the relation found between calcium supplement consumption and calcific shoulder tendonitis. Methods: This analytical-descriptive study was conducted on 250 patients with shoulder pain referring to clinics and emergency department of Shohada Orthopedics Hospital during one year for considering calcific shoulder tendonitis and calcium supplement consumption. Patients with calcific tendonitis were treated and their functional ability was evaluated using DASH questionnaire, pain severity and range of motion (ROM before and after treatment and their correlation with calcium supplement consumption. Results: Calcific tendonitis and calcium consumption were generally seen in 30 (12% and 73 (29.2% cases, respectively. Calcium consumption frequency in patients with calcific tendonitis was significantly higher than the patients who did not consume calcium supplements (76.7% vs. 22.7%. Patients with calcific tendonitis who did not consume calcium supplements suffered from significantly longer periods of shoulder pain. All patients having consumed calcium supplement were female. The group who consumed calcium supplement had significantly severe pain and higher DASH score before and after treatment, while there was no significant difference in number of impaired ROM before and after treatment. Also, there was a negative correlation between calcium supplement consumption, pain severity and DASH score before and after treatment. Conclusion: Calcium supplement consumption is related to calcific tendonitis and is also accompanied with more pain and lower functional ability in patients with calcific tendonitis.    Keywords: Calcific tendonitis; Shoulder; Calcium supplement; Pain

Paradiaphyseal calcific tendinitis with cortical bone erosion.

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Fritz, P; Bardin, T; Laredo, J D; Ziza, J M; D'Anglejan, G; Lansaman, J; Bucki, B; Forest, M; Kuntz, D

1994-05-01

To determine the clinical, radiologic, and histologic features of calcific tendinitis with cortical bone erosion. The records of 6 patients with paradiaphyseal calcific tendinitis and adjacent bone cortex erosion were reviewed. Calcific tendinitis involved the linea aspera in 4 patients, the bicipital groove in 1 patient, and the deltoid insertion in another. Calcium deposits were associated with cortical bone erosions, revealed on plain radiographs in 4 patients and computed tomography scans in 2. Bone scans were performed in 2 patients and showed local hyperfixation of the isotope. In 4 patients, suspicion of a neoplasm led to a biopsy. Calcium deposits appeared to be surrounded by a foreign body reaction with numerous giant cells. Apatite crystals were identified by transmission electron microscopy and elemental analysis in 1 surgical sample. Paradiaphyseal calcific tendinitis with cortical bone erosion is an uncommon presentation of apatite deposition disease.

Skeletal maturity assessment using mandibular canine calcification stages

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Vildana Džemidžić

2016-11-01

Full Text Available Objective. The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. Materials and methods. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years. The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI, as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Results. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. Conclusions. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase.

Tracheobronchial calcification in adult health study subjects

International Nuclear Information System (INIS)

Fukuya, Tatsuro; Mihara, Futoshi; Kudo, Sho; Russell, W.J.; Delongchamp, R.R.; Vaeth, M.; Hosoda, Yutaka.

1988-04-01

Tracheobronchial calcification is reportedly more frequent in women than in men. Ten cases of extensive tracehobronchial calcification were identified on chest radiographs of 1,152 consecutively examined Adult Health Study subjects, for a prevalence of 0.87 %. An additional 51 subjects having this coded diagnosis were identified among 11,758 members of this fixed population sample. Sixty of the 61 subjects were women. The manifestations and extent of this type of calcification and its correlations with clinical and histopathologic features, which have not been previously reported, are described here. (author)

Premature Calcifications of Costal Cartilages: A New Perspective Premature Calcifications of Costal Cartilages: A New Perspective

International Nuclear Information System (INIS)

Rhomberg, W.; Schuster, A.

2014-01-01

Calcifications of the costal cartilages occur, as a rule, not until the age of 30 years. The knowledge of the clinical significance of early and extensive calcifications is still incomplete. Materials and Methods. A search was made to find patients below the age of 30 years who showed distinct calcifications of their lower costal cartilages by viewing 360 random samples of intravenous pyelograms and abdominal plain films. The histories, and clinical and laboratory findings of these patients were analyzed. Results. Nineteen patients fulfilled the criteria of premature calcifications of costal cartilages (CCCs). The patients had in common that they were frequently referred to a hospital and were treated by several medical disciplines. Nevertheless many complaints of the patients remained unsolved. Premature CCCs were often associated with rare endocrine disorders, inborn errors of metabolism, and abnormal hematologic findings. Among the metabolic disorders there were 2 proven porphyrias and 7 patients with a suspected porphyria but with inconclusive laboratory findings. Conclusion. Premature CCCs are unlikely to be a normal variant in skeletal radiology. The findings in this small group of patients call for more intensive studies, especially in regard to the putative role of a porphyria

Susceptibility weighted imaging: differentiating between calcification and hemosiderin

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Barbosa, Jeam Haroldo Oliveira; Salmon, Carlos Ernesto Garrido, E-mail: jeamharoldo@hotmail.com [Universidade de Sao Paulo (FFCLRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras; Santos, Antonio Carlos [Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina

2015-03-15

Objective: to present a detailed explanation on the processing of magnetic susceptibility weighted imaging (SWI), demonstrating the effects of echo time and sensitive mask on the differentiation between calcification and hemosiderin. Materials and methods: computed tomography and magnetic resonance (magnitude and phase) images of six patients (age range 41-54 years; four men) were retrospectively selected. The SWI images processing was performed using the Matlab's own routine. Results: four out of the six patients showed calcifications at computed tomography images and their SWI images demonstrated hyperintense signal at the calcification regions. The other patients did not show any calcifications at computed tomography, and SWI revealed the presence of hemosiderin deposits with hypointense signal. Conclusion: the selection of echo time and of the mask may change all the information on SWI images, and compromise the diagnostic reliability. Amongst the possible masks, the authors highlight that the sigmoid mask allows for contrasting calcifications and hemosiderin on a single SWI image. (author)

The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

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Omoigui Sota

2007-03-01

Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

Calcifications simulating peroneus longus tendinitis

International Nuclear Information System (INIS)

Carvalho, A. de; Illum, F.; Joergensen, J.

1984-01-01

In two patients with sprains of the ankle joint calcification adjacent to the posterior tibial margin was evident in the lateral projection of a standard radiographic examination. Calcifying peroneus longus tendinitis was suggested. Further tangential views and computed tomography (CT) scan disclosed, however, that the calcifications in both patients were located in the tibial insertion of the posterior and inferior tibio-fibular ligament. In such cases, a correct diagnosis will avoid unnecessary treatment for a non-existent tendinitis. (orig.)

Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

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Keshav Raj Paudel

2016-01-01

Full Text Available The levels of circulating microparticles (MPs are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs described as complex submicron (0.1 to 1.0 μm vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.

Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.

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Nicolas, Gaël; Pottier, Cyril; Charbonnier, Camille; Guyant-Maréchal, Lucie; Le Ber, Isabelle; Pariente, Jérémie; Labauge, Pierre; Ayrignac, Xavier; Defebvre, Luc; Maltête, David; Martinaud, Olivier; Lefaucheur, Romain; Guillin, Olivier; Wallon, David; Chaumette, Boris; Rondepierre, Philippe; Derache, Nathalie; Fromager, Guillaume; Schaeffer, Stéphane; Krystkowiak, Pierre; Verny, Christophe; Jurici, Snejana; Sauvée, Mathilde; Vérin, Marc; Lebouvier, Thibaud; Rouaud, Olivier; Thauvin-Robinet, Christel; Rousseau, Stéphane; Rovelet-Lecrux, Anne; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

2013-11-01

Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: 60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis

Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

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Shahida A. Khan

2014-01-01

Full Text Available Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs and G protein coupled receptors (GPCRs. In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.

Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis.

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Cochain, Clément; Vafadarnejad, Ehsan; Arampatzi, Panagiota; Jaroslav, Pelisek; Winkels, Holger; Ley, Klaus; Wolf, Dennis; Saliba, Antoine-Emmanuel; Zernecke, Alma

2018-03-15

Rationale: It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they ha ve been defined by the expression of a restricted number of markers. Objective: We have applied single-cell RNA-seq as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. Methods and Results: We performed single-cell RNA sequencing of total aortic CD45 + cells extracted from the non-diseased (chow fed) and atherosclerotic (11 weeks of high fat diet) aorta of Ldlr -/- mice. Unsupervised clustering singled out 13 distinct aortic cell clusters. Among the myeloid cell populations, Resident-like macrophages with a gene expression profile similar to aortic resident macrophages were found in healthy and diseased aortae, whereas monocytes, monocyte-derived dendritic cells (MoDC), and two populations of macrophages were almost exclusively detectable in atherosclerotic aortae, comprising Inflammatory macrophages showing enrichment in I l1b , and previously undescribed TREM2 hi macrophages. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these three macrophage subsets and MoDC, and uncovered putative functions of each cell type. Notably, TREM2 hi macrophages appeared to be endowed with specialized functions in lipid metabolism and catabolism, and presented a gene expression signature reminiscent of osteoclasts, suggesting a role in lesion calcification. TREM2 expression was moreover detected in human lesional macrophages. Importantly, these macrophage populations were present also in advanced atherosclerosis and in Apoe -/- aortae, indicating relevance of our findings in different stages of atherosclerosis and mouse models. Conclusions: These data unprecedentedly uncovered the transcriptional landscape and phenotypic

The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

DEFF Research Database (Denmark)

Thomsen, Henrik Holm; Møller, Holger Jon; Trolle, Christian

2013-01-01

Soluble CD163 (sCD163) is a novel marker linked to states of low grade inflammation such as diabetes, obesity, liver disease and atherosclerosis, all prevalent in subjects with Turner and Klinefelter Syndromes. We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards...

Tumor-like calcifications with scleroderma

International Nuclear Information System (INIS)

Meyer, E.; Kulenkampff, H.A.; Kortenhaus, H.

1987-01-01

In patients with progressive scleroderma, interstitial calcifications are present to a varying extent. They are mostly located in the soft tissues of the fingers, resembling points, commas or dashes. They may also appear as 'calcinosis universalis' and reach a considerable size. Thus they mimic proliferative tumors. Scintigraphy, proving the existence of further calcifications can be helpful. We report the case of a female patient who presented with such a 'pseudotumor' of unusual size, site and extent in the lumbar region. (orig.) [de

Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice.

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Thomas E Sussan

Full Text Available BACKGROUND: Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf2(-/- causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis. PRINCIPAL FINDINGS: To investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf2(-/- mice with apoliporotein E-deficient (ApoE(-/- mice. ApoE(-/- and ApoE(-/-Nrf2(-/- mice were fed an atherogenic diet for 20 weeks, and plaque area was assessed in the aortas. Surprisingly, ApoE(-/-Nrf2(-/- mice exhibited significantly smaller plaque area than ApoE(-/- controls (11.5% vs 29.5%. This decrease in plaque area observed in ApoE(-/-Nrf2(-/- mice was associated with a significant decrease in uptake of modified low density lipoproteins (AcLDL by isolated macrophages from ApoE(-/-Nrf2(-/- mice. Furthermore, atherosclerotic plaques and isolated macrophages from ApoE(-/-Nrf2(-/- mice exhibited decreased expression of the scavenger receptor CD36. CONCLUSIONS: Nrf2 is pro-atherogenic in mice, despite its antioxidative function. The net pro-atherogenic effect of Nrf2 may be mediated via positive regulation of CD36. Our data demonstrates that the potential effects of Nrf2-targeted therapies on cardiovascular disease need to be investigated.

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH).

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Gandaglia, Giorgio; Briganti, Alberto; Gontero, Paolo; Mondaini, Nicola; Novara, Giacomo; Salonia, Andrea; Sciarra, Alessandro; Montorsi, Francesco

2013-08-01

Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation. © 2013 BJU International.

Atherosclerosis: Hypotheses and theories

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E. A. Yuryeva

2014-01-01

Full Text Available The article gives basic theories of the pathogenesis of atherosclerosis, including inflammatory, cholesterol, lipid, lipoprotein, iron ones, as a result of metabolic syndrome, oxidative stress. In spite of carefully and deeply developed and ongoing elaborated pathogenesis theories, the etiological factors of atherosclerosis remain unknown so far. The age-related aspect of the disease is discussed; atherosclerosis is considered to be a childhood-onset disease that manifests itself at a later age. The authors propose an experimental and clinical evidence-based concept of the common etiology of syndromes of atherosclerosis, namely: the body's endogenous intoxication that is permanent or periodically progressive may be a primary cause of altered conformation of different protein molecules with their higher ability to adsorb the trace elements consolidating the structural changes. This change of proteins diminishes their functions and determines their antigenic properties, which is attended by the development of different pathogenic components in relation to the body's individual features.

Imaging findings in acute calcific prevertebral tendinitis

International Nuclear Information System (INIS)

Grassi, Caio Giometti; Diniz, Fabio de Vilhena; Garcia, Marcio Ricardo Taveira; Gomes, Regina Lucia Elia; Daniel, Mauro Miguel; Funari, Marcelo Buarque de Gusmao

2011-01-01

Acute calcific prevertebral tendinitis is a benign and rare condition that presents calcification of the superior oblique fibers of longus colli muscle with local inflammatory reaction. Such condition is one of the less common presentations of calcium hydroxyapatite deposition disease. Clinical signs are usually acute neck pain and odynophagia, and it may be misdiagnosed as retropharyngeal abscess, spondylodiscitis or traumatic injury. The imaging findings in calcific prevertebral tendinitis are pathognomonic. The knowledge of such findings is extremely important to avoid unnecessary interventions in a patient presenting a condition with a good response to conservative treatment. (author)

Imaging findings in acute calcific prevertebral tendinitis

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Grassi, Caio Giometti; Diniz, Fabio de Vilhena; Garcia, Marcio Ricardo Taveira; Gomes, Regina Lucia Elia; Daniel, Mauro Miguel; Funari, Marcelo Buarque de Gusmao [Hospital Israelita Albert Einstein (HIAE), Sao Paulo, SP (Brazil). Imaging Dept.

2011-09-15

Acute calcific prevertebral tendinitis is a benign and rare condition that presents calcification of the superior oblique fibers of longus colli muscle with local inflammatory reaction. Such condition is one of the less common presentations of calcium hydroxyapatite deposition disease. Clinical signs are usually acute neck pain and odynophagia, and it may be misdiagnosed as retropharyngeal abscess, spondylodiscitis or traumatic injury. The imaging findings in calcific prevertebral tendinitis are pathognomonic. The knowledge of such findings is extremely important to avoid unnecessary interventions in a patient presenting a condition with a good response to conservative treatment. (author)

Food-derived bioactive peptides on inflammation and oxidative stress.

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Chakrabarti, Subhadeep; Jahandideh, Forough; Wu, Jianping

2014-01-01

Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions. Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

Association of gastrocnemius tendon calcification with chondrocalcinosis of the knee

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Foldes, K. [Department of Radiology, Veterans Administration Medical Center (VAMC), San Diego, CA (United States)]|[University of California San Diego Medical Center (UCSD), San Diego, CA (United States)]|[National Institute of Rheumatology and Physiotherapy, Budapest (Hungary); Lenchik, L. [Department of Radiology, Veterans Administration Medical Center (VAMC), San Diego, CA (United States)]|[University of California San Diego Medical Center (UCSD), San Diego, CA (United States); Jaovisidha, S. [Department of Radiology, Veterans Administration Medical Center (VAMC), San Diego, CA (United States)]|[University of California San Diego Medical Center (UCSD), San Diego, CA (United States); Clopton, P. [Department of Radiology, Veterans Administration Medical Center (VAMC), San Diego, CA (United States); Sartoris, D.J. [Department of Radiology, Veterans Administration Medical Center (VAMC), San Diego, CA (United States)]|[University of California San Diego Medical Center (UCSD), San Diego, CA (United States); Resnick, D. [Department of Radiology, Veterans Administration Medical Center (VAMC), San Diego, CA (United States)]|[University of California San Diego Medical Center (UCSD), San Diego, CA (United States)

1996-10-01

Objective. Chondrocalcinosis of the knee is a common radiological finding in the elderly. However, visualization of chondrocalcinosis may be difficult in patients with advanced cartilage loss.The purpose of this study was to determine sensitivity, specificity, and accuracy of gastrocnemius tendon calcification that might serve as a radiographic marker of chondrocalcinosis in patients with painful knees. Design and patients. We prospectively evaluated 37 knee radiographs in 30 consecutive patients (29 men, 8 women; mean age 67 years, age range 37-90 years) with painful knees who had radiographic evidence of chondrocalcinosis. The frequency of fibrocartilage, hyaline cartilage, and gastrocnemius tendon calcification was determined. For a control group, we evaluated knee radiographs in 65 consecutive patients with knee pain (54 men, 11 women; mean age 59 years, age range 40-93 years) who had no radiological signs of chondrocalcinosis. The frequency of gastrocnemius tendon calcification in the control group was determined. Results. Gastrocnemius tendon calcification was 41% sensitive, 100% specific, and 78% accurate in predicting chondrocalcinosis. The gastrocnemius tendon was calcified on 15 of 37 (41%) radiographs in the experimental group and on 0 of 67 radiographs in the control group. In the chondrocalcinosis group, 23 (62%) had posterior hyaline cartilage calcification, 14 (38%) had anterior hyaline cartilage calcification, 31 (84%) had medial meniscus calcification, and 36 (97%) had lateral meniscus calcification. Conclusions. Our results show that gastrocnemius tendon calcification is an accurate radiographic marker of chondrocalcinosis in patients with knee pain. (orig.). With 2 figs., 2 tabs.

Association of gastrocnemius tendon calcification with chondrocalcinosis of the knee

International Nuclear Information System (INIS)

Foldes, K.; Lenchik, L.; Jaovisidha, S.; Clopton, P.; Sartoris, D.J.; Resnick, D.

1996-01-01

Objective. Chondrocalcinosis of the knee is a common radiological finding in the elderly. However, visualization of chondrocalcinosis may be difficult in patients with advanced cartilage loss.The purpose of this study was to determine sensitivity, specificity, and accuracy of gastrocnemius tendon calcification that might serve as a radiographic marker of chondrocalcinosis in patients with painful knees. Design and patients. We prospectively evaluated 37 knee radiographs in 30 consecutive patients (29 men, 8 women; mean age 67 years, age range 37-90 years) with painful knees who had radiographic evidence of chondrocalcinosis. The frequency of fibrocartilage, hyaline cartilage, and gastrocnemius tendon calcification was determined. For a control group, we evaluated knee radiographs in 65 consecutive patients with knee pain (54 men, 11 women; mean age 59 years, age range 40-93 years) who had no radiological signs of chondrocalcinosis. The frequency of gastrocnemius tendon calcification in the control group was determined. Results. Gastrocnemius tendon calcification was 41% sensitive, 100% specific, and 78% accurate in predicting chondrocalcinosis. The gastrocnemius tendon was calcified on 15 of 37 (41%) radiographs in the experimental group and on 0 of 67 radiographs in the control group. In the chondrocalcinosis group, 23 (62%) had posterior hyaline cartilage calcification, 14 (38%) had anterior hyaline cartilage calcification, 31 (84%) had medial meniscus calcification, and 36 (97%) had lateral meniscus calcification. Conclusions. Our results show that gastrocnemius tendon calcification is an accurate radiographic marker of chondrocalcinosis in patients with knee pain. (orig.). With 2 figs., 2 tabs

Inhibitory role of Notch1 in calcific aortic valve disease.

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Asha Acharya

Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

Science.gov (United States)

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Inflammation and premature aging in advanced chronic kidney disease.

Science.gov (United States)

Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

2017-10-01

Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

Significance of coronary artery calcification detected incidentally with chest CT

International Nuclear Information System (INIS)

Moore, E.H.; Greenberg, R.; Miller, S.W.; Shepard, J.O.; Bourgouin, P.M.; McLoud, T.C.

1987-01-01

Coronary artery calcifications are well seen on CT scans because of high contrast resolution. Individual vessels were scored 0-3+ based on degree of calcification in over 40 patients who also underwent cardiac catheterization. Though relatively insensitive, the presence of dense calcifications had a specificity of roughly 60% to 70% for the presence of severe stenosis. In addition, 30 patients with calcification on CT scans and 30 age-matched controls, all of whom underwent thoracotomy, were compared with respect to prior cardiac history, estimated anesthetic risk, and postoperative cardiac complications. Patients with calcifications were more likely to have evidence of coronary disease and/or encounter postoperative cardiac complications

Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

Science.gov (United States)

Madan, Monika; Amar, Salomon

2008-09-12

Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g) (10(7) CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE(+/-)-TLR2(+/+) mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/-)-TLR2(+/+) mice were significantly higher than from ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/-)-TLR2(+/+) mice compared to ApoE(+/-)-TLR2(+/-) and TLR2(-/-) mice, irrespective of diet or bacterial challenge. ApoE(+/-)-TLR2(+/+) mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/-)-TLR2(-/-) mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/-)-TLR2(+/+) mice

Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

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Monika Madan

2008-09-01

Full Text Available Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/- mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/--TLR2(+/+, ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g (10(7 CFU or vehicle (normal saline. Animals were euthanized 24 weeks after the first inoculation. ApoE(+/--TLR2(+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/--TLR2(+/+ mice were significantly higher than from ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/--TLR2(+/+ mice compared to ApoE(+/--TLR2(+/- and TLR2(-/- mice, irrespective of diet or bacterial challenge. ApoE(+/--TLR2(+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/--TLR2(-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/--TLR2(+/+ mice fed the high fat

Breast skin calcifications: Mammographic recognition and confirmation

International Nuclear Information System (INIS)

Berkowitz, J.E.; Gatewood, O.M.B.; Gayler, B.W.

1987-01-01

The authors found microcalcifications in the skin of the breast to occur in 8% of patients undergoing mammography, a prevalence much higher than what has been previously reported. Usually in incidental finding, breast skin calcifications are readily recognized when they are multiple, bilateral, coarse, or polygonal with a central radiolucency; when they are located in a peripheral portion of the breast on at least one view, or when they are serendipitously imaged within the skin. One hundred patients with breast skin calcifications were studied. In 15 patients in whom clustered dermal calcifications simulated parenchymal microcalcifications, template-guided tangential views permitted precise skin localization. Three of those patients had been referred for needle localization before biopsy and four after failed biopsy for clustered microcalcifications. Dermal calcifications can pose a vexing problem in the management of microcalcifications of the breast. A high index of suspicion is warrented in order to forestall unnecessary or unsuccessful biopsies

Dual-energy digital mammography for calcification imaging: Scatter and nonuniformity corrections

International Nuclear Information System (INIS)

Kappadath, S. Cheenu; Shaw, Chris C.

2005-01-01

Mammographic images of small calcifications, which are often the earliest signs of breast cancer, can be obscured by overlapping fibroglandular tissue. We have developed and implemented a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available aSi:H/CsI:Tl flat-panel based digital mammography system. The low- and high-energy images were combined using a nonlinear mapping function to cancel the tissue structures and generate the dual-energy (DE) calcification images. The total entrance-skin exposure and mean-glandular dose from the low- and high-energy images were constrained so that they were similar to screening-examination levels. To evaluate the DE calcification image, we designed a phantom using calcium carbonate crystals to simulate calcifications of various sizes (212-425 μm) overlaid with breast-tissue-equivalent material 5 cm thick with a continuously varying glandular-tissue ratio from 0% to 100%. We report on the effects of scatter radiation and nonuniformity in x-ray intensity and detector response on the DE calcification images. The nonuniformity was corrected by normalizing the low- and high-energy images with full-field reference images. Correction of scatter in the low- and high-energy images significantly reduced the background signal in the DE calcification image. Under the current implementation of DEDM, utilizing the mammography system and dose level tested, calcifications in the 300-355 μm size range were clearly visible in DE calcification images. Calcification threshold sizes decreased to the 250-280 μm size range when the visibility criteria were lowered to barely visible. Calcifications smaller than ∼250 μm were usually not visible in most cases. The visibility of calcifications with our DEDM imaging technique was limited by quantum noise, not system noise

Evaluation of laryngeal cartilage calcification in computed tomography

International Nuclear Information System (INIS)

Laskowska, K.; Serafin, Z.; Lasek, W.; Maciejewski, M.; Wieczor, W.; Wisniewski, S.

2008-01-01

Computed tomography (CT) is one of the basic methods used for laryngeal carcinoma diagnostics. Osteosclerotic and osteolytic changes of the cartilages are considered as a common radiologic symptom of laryngeal neoplasms. The aim of this paper was to evaluate the prevalence of both osteosclerotic changes and focal calcification defects, which may be suggestive of osteolysis. Calcification was assessed in the thyroid, the cricoid and the arytenoids cartilages on CT images of the neck. We have retrospectively analyzed neck CT examinations of 50 patients without any laryngeal pathology in anamnesis. The grade and symmetry of calcifications was assessed in the thyroid, the cricoid and the arytenoids cartilages. Calcification of the laryngeal cartilages was present in 83% of the patients. Osteosclerotic lesions of the thyroid cartilage were seen in 70% of the patients (asymmetric in 60% of them), of the cricoid catrilage in 50% (asymmetric in 60%), and of the arytenoid cartilages in 24% (asymmetric in 67%). Focal calcification defects were present in the thyroid cartilage in 56% of the patients (asymmetric in 67% of them), in the cricoid catrilage in 8% (asymmetric in all cases), and in the arytenoid cartilages in 20% (asymmetric in 90%). Osteosclerotic changes and focal calcification defects, which may suggest osteolysis, were found in most of the patients. Therefore, they cannot be used as crucial radiological criteria of neoplastic invasion of laryngeal cartilages. (authors)

Coffee consumption and coronary calcification: The Rotterdam coronary calcification study

NARCIS (Netherlands)

G.J. van Woudenbergh (Geertruida); R. Vliegenthart (Rozemarijn); F.J.A. van Rooij (Frank); A. Hofman (Albert); M. Oudkerk (Matthijs); J.C.M. Witteman (Jacqueline); J.M. Geleijnse (Marianne)

2008-01-01

textabstractBACKGROUND - The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. METHODS AND RESULTS - The study involved 1570 older men and women without coronary heart disease who

Overexpression of PTPN2 in Visceral Adipose Tissue Ameliorated Atherosclerosis via T Cells Polarization Shift in Diabetic Apoe-/- Mice

Directory of Open Access Journals (Sweden)

Ya Li

2018-03-01

Full Text Available Background/Aims: Dysregulated inflammation in adipose tissue, marked by increased pro-inflammatory T-cell accumulation and reduced regulatory T cells (Treg, contributes to diabetes-associated insulin resistance and atherosclerosis. However, the molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown. Methods: Sixty apolipoprotein E (ApoE-/- mice were randomly divided into chow and diabetes groups. Diabetes was induced by a high-fat and high-sugar diet combined with low-dose streptozotocin. Then we transferred a recombinant adenovirus carrying the protein tyrosine phosphatase non-receptor type 2 (PTPN2 gene into epididymal white adipose tissue (EWAT of ApoE-/- mice. After transfection, all mice were euthanized to evaluate the effects of PTPN2 on T cells polarization and atherosclerosis. Results: PTPN2 was downregulated in EWAT of diabetic ApoE-/- mice. PTPN2 overexpression in EWAT reversed the high Th1/Treg and Th17/Treg ratios in EWAT of diabetic mice. In addition, PTPN2 overexpression in EWAT could significantly reduce macrophages infiltration, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines in EWAT, improving insulin resistance. In aortic root lesions, the vulnerability index were significantly decreased by overexpression of PTPN2 in EWAT. Conclusion: These data suggested that PTPN2 overexpression in EWAT would inhibit systemic inflammation and increase the plaque stability via T cells polarization shift in diabetic mice.

The role of T and B cells in human atherosclerosis and atherothrombosis.

Science.gov (United States)

Ammirati, E; Moroni, F; Magnoni, M; Camici, P G

2015-02-01

Far from being merely a passive cholesterol accumulation within the arterial wall, the development of atherosclerosis is currently known to imply both inflammation and immune effector mechanisms. Adaptive immunity has been implicated in the process of disease initiation and progression interwined with traditional cardiovascular risk factors. Although the body of knowledge regarding the correlation between atherosclerosis and immunity in humans is growing rapidly, a relevant proportion of it derives from studies carried out in animal models of cardiovascular disease (CVD). However, while the mouse is a well-suited model, the results obtained therein are not fully transferrable to the human setting due to intrinsic genomic and environmental differences. In the present review, we will discuss mainly human findings, obtained either by examination of post-mortem and surgical atherosclerotic material or through the analysis of the immunological profile of peripheral blood cells. In particular, we will discuss the findings supporting a pro-atherogenic role of T cell subsets, such as effector memory T cells or the potential protective function of regulatory T cells. Recent studies suggest that traditional T cell-driven B2 cell responses appear to be atherogenic, while innate B1 cells appear to exert a protective action through the secretion of naturally occurring antibodies. The insights into the immune pathogenesis of atherosclerosis can provide new targets in the quest for novel therapeutic targets to abate CVD morbidity and mortality. © 2014 British Society for Immunology.

Does high C-reactive protein concentration increase atherosclerosis? The Whitehall II Study.

Directory of Open Access Journals (Sweden)

Mika Kivimäki

Full Text Available BACKGROUND: C-reactive protein (CRP, a marker of systemic inflammation, is associated with risk of coronary events and sub-clinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 3 tag single nucleotide polymorphisms (SNPs [+1444T>C (rs1130864; +2303G>A (rs1205 and +4899T>G (rs 3093077] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT, a structural marker of atherosclerosis, in 4941 men and women aged 50-74 (mean 61 years (the Whitehall II Study. The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT. CONCLUSIONS/SIGNIFICANCE: Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal.

Coccolithophore growth and calcification in a changing ocean

Science.gov (United States)

Krumhardt, Kristen M.; Lovenduski, Nicole S.; Iglesias-Rodriguez, M. Debora; Kleypas, Joan A.

2017-12-01

Coccolithophores are the most abundant calcifying phytoplankton in the ocean. These tiny primary producers have an important role in the global carbon cycle, substantially contributing to global ocean calcification, ballasting organic matter to the deep sea, forming part of the marine food web base, and influencing ocean-atmosphere CO2 exchange. Despite these important impacts, coccolithophores are not explicitly simulated in most marine ecosystem models and, therefore, their impacts on carbon cycling are not represented in most Earth system models. Here, we compile field and laboratory data to synthesize overarching, across-species relationships between environmental conditions and coccolithophore growth rates and relative calcification (reported as a ratio of particulate inorganic carbon to particulate organic carbon in coccolithophore biomass, PIC/POC). We apply our relationships in a generalized coccolithophore model, estimating current surface ocean coccolithophore growth rates and relative calcification, and projecting how these may change over the 21st century using output from the Community Earth System Model large ensemble. We find that average increases in sea surface temperature of ∼ 2-3 ° C lead to faster coccolithophore growth rates globally (> 10% increase) and increased calcification at high latitudes. Roughly an ubiquitous doubling of surface ocean pCO2 by the end of the century has the potential to moderately stimulate coccolithophore growth rates, but leads to reduced calcification (∼ 25% decrease). Decreasing nutrient availability (from warming-induced increases in stratification) produces increases in relative calcification, but leads to ∼ 25% slower growth rates. With all drivers combined, we observe decreases in calcification and growth in most low and mid latitude regions, with possible increases in both of these responses in most high latitude regions. Major limitations of our coccolithophore model stem from a lack of conclusive

Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study.

Science.gov (United States)

Kudo, Chieko; Shin, Wee Soo; Minabe, Masato; Harai, Kazuo; Kato, Kai; Seino, Hiroaki; Goke, Eiji; Sasaki, Nobuhiro; Fujino, Takemasa; Kuribayashi, Nobuichi; Pearce, Youko Onuki; Taira, Masato; Maeda, Hiroshi; Takashiba, Shogo

2015-09-01

It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut-off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease.

Pulp Calcification in Traumatized Primary Teeth - Classification, Clinical And Radiographic Aspects.

Science.gov (United States)

Mello-Moura, Anna Carolina Volpi; Santos, Ana Maria Antunes; Bonini, Gabriela Azevedo Vasconcelos Cunha; Zardetto, Cristina Giovannetti Del Conte; Moura-Netto, Cacio; Wanderley, Marcia Turolla

The aim of this study was to standardize the nomenclature of pulp alteration to pulp calcification (PC) and to classify it according to type, quantity and location, as well as relate it to clinical and radiographic features. The dental records of 946 patients from the Research and Clinical Center for Dental Trauma in Primary Teeth were studied. Two hundred and fifty PC-traumatized upper deciduous incisors were detected. According to radiographic analysis of the records, 62.5% showed diffuse calcification, 36.3% tube-like calcification, and 1.2% concentric calcification. According to the extension of pulp calcification, the records showed: 80% partial calcification, 17.2% total coronal calcification and partial radicular calcification, and 2.8 % total coronal and radicular calcification. As for location, only 2.4% were on the coronal pulp, 5.2% on the radicular pulp and 92.4% on both radicular and coronal pulp. Regarding coronal discoloration, 54% were yellow and 2% gray. In relation to periradicular changes, 10% showed widened periodontal ligament space, 3.1% internal resorption, 10% external resorption, 10.4% periapical bone rarefaction. Since PC is a general term, it is important to classify it and correlate it to clinical and radiographic changes, in order to establish the correct diagnosis, treatment and prognosis of each case.

Coffee consumption and coronary calcification - The Rotterdam Coronary Calcification Study

NARCIS (Netherlands)

van Woudenbergh, Geertruida J.; Vliegenthart, Rozemarijn; van Rooij, Frank J. A.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jacqueline C. M.; Geleijnse, Johanna M.

Background-The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. Methods and Results-The study involved 1570 older men and women without coronary heart disease who participated in the

Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables

DEFF Research Database (Denmark)

Hansen, B F; Mortensen, A; Hansen, J F

1994-01-01

estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19......-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity...... was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable....

Chronic Intermittent Hypoxia Induces Atherosclerosis

OpenAIRE

Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

2007-01-01

Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors

Science.gov (United States)

Hu, Desheng; Mohanta, Sarajo K.; Yin, Changjun; Peng, Li; Ma, Zhe; Srikakulapu, Prasad; Grassia, Gianluca; MacRitchie, Neil; Dever, Gary; Gordon, Peter; Burton, Francis L.; Ialenti, Armando; Sabir, Suleman R.; McInnes, Iain B.; Brewer, James M.; Garside, Paul; Weber, Christian; Lehmann, Thomas; Teupser, Daniel; Habenicht, Livia; Beer, Michael; Grabner, Rolf; Maffia, Pasquale; Weih, Falk; Habenicht, Andreas J.R.

2015-01-01

Summary Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs. PMID:26084025

Acute Calcific Tendinitis of the Index Finger in a Child.

Science.gov (United States)

Walocko, Frances M; Sando, Ian C; Haase, Steven C; Kozlow, Jeffrey H

2017-09-01

Calcific tendinitis is characterized by calcium hydroxyapatite crystal deposition within tendons and is a common cause of musculoskeletal pain in adults. Its clinical manifestations may be acute, chronic, or asymptomatic. Acute calcific tendinitis is self-resolving condition that is rarely reported in the pediatric population and may be overlooked for more common processes, leading to unnecessary treatment. A chart reivew was performed of a single case of acute calcific tendonitis of the index finger in a child. We describe a case of calcific tendinitis of the index finger in a 9-year-old boy who was referred to us for a second opinion after surgical exploration of an acutely inflamed digit was recommended based on his initial presentation. The calcifications and symptoms resolved over time without operative management. Although rare in children, acute calcific tendinitis can present similar to an infection. However, appropriate managment is non-operative as the symptoms and radiographic findings resolve over time.

Coral calcification and ocean acidification

Science.gov (United States)

Jokiel, Paul L.; Jury, Christopher P.; Kuffner, Ilsa B.

2016-01-01

Over 60 years ago, the discovery that light increased calcification in the coral plant-animal symbiosis triggered interest in explaining the phenomenon and understanding the mechanisms involved. Major findings along the way include the observation that carbon fixed by photosynthesis in the zooxanthellae is translocated to animal cells throughout the colony and that corals can therefore live as autotrophs in many situations. Recent research has focused on explaining the observed reduction in calcification rate with increasing ocean acidification (OA). Experiments have shown a direct correlation between declining ocean pH, declining aragonite saturation state (Ωarag), declining [CO32_] and coral calcification. Nearly all previous reports on OA identify Ωarag or its surrogate [CO32] as the factor driving coral calcification. However, the alternate “Proton Flux Hypothesis” stated that coral calcification is controlled by diffusion limitation of net H+ transport through the boundary layer in relation to availability of dissolved inorganic carbon (DIC). The “Two Compartment Proton Flux Model” expanded this explanation and synthesized diverse observations into a universal model that explains many paradoxes of coral metabolism, morphology and plasticity of growth form in addition to observed coral skeletal growth response to OA. It is now clear that irradiance is the main driver of net photosynthesis (Pnet), which in turn drives net calcification (Gnet), and alters pH in the bulk water surrounding the coral. Pnet controls [CO32] and thus Ωarag of the bulk water over the diel cycle. Changes in Ωarag and pH lag behind Gnet throughout the daily cycle by two or more hours. The flux rate Pnet, rather than concentration-based parameters (e.g., Ωarag, [CO3 2], pH and [DIC]:[H+] ratio) is the primary driver of Gnet. Daytime coral metabolism rapidly removes DIC from the bulk seawater. Photosynthesis increases the bulk seawater pH while providing the energy that drives

Differential Effects of Ocean Acidification on Coral Calcification: Insights from Geochemistry.

Science.gov (United States)

Holcomb, M.; Decarlo, T. M.; Venn, A.; Tambutte, E.; Gaetani, G. A.; Tambutte, S.; Allemand, D.; McCulloch, M. T.

2014-12-01

Although ocean acidification is expected to negatively impact calcifying animals due to the formation of CaCO3 becoming less favorable, experimental evidence is mixed. Corals have received considerable attention in this regard; laboratory culture experiments show there to be a wide array of calcification responses to acidification. Here we will show how relationships for the incorporation of various trace elements and boron isotopes into synthetic aragonite can be used to reconstruct carbonate chemistry at the site of calcification. In turn the chemistry at the site of calcification can be determined under different ocean acidification scenarios and differences in the chemistry at the site of calcification linked to different calcification responses to acidification. Importantly we will show that the pH of the calcifying fluid alone is insufficient to estimate calcification responses, thus a multi-proxy approach using multiple trace elements and isotopes is required to understand how the site of calcification is affected by ocean acidification.

Association Between Osteogenesis and Inflammation During the Progression of Calcified Plaque Evaluated by 18F-Fluoride and 18F-FDG.

Science.gov (United States)

Li, Xiang; Heber, Daniel; Cal-Gonzalez, Jacobo; Karanikas, Georgios; Mayerhoefer, Marius E; Rasul, Sazan; Beitzke, Dietrich; Zhang, Xiaoli; Agis, Hermine; Mitterhauser, Markus; Wadsak, Wolfgang; Beyer, Thomas; Loewe, Christian; Hacker, Marcus

2017-06-01

18 F-FDG is the most widely validated PET tracer for the evaluation of atherosclerotic inflammation. Recently, 18 F-NaF has also been considered a potential novel biomarker of osteogenesis in atherosclerosis. We aimed to analyze the association between inflammation and osteogenesis at different stages of atherosclerosis, as well as the interrelationship between these 2 processes during disease progression. Methods: Thirty-four myeloma patients underwent 18 F-NaF and 18 F-FDG PET/CT examinations. Lesions were divided into 3 groups (noncalcified, mildly calcified, and severely calcified lesions) on the basis of calcium density as measured in Hounsfield units by CT. Tissue-to-background ratios were determined from PET for both tracers. The association between inflammation and osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least 2 examinations with both tracers. Results: There were significant correlations between the maximum tissue-to-background ratios of the 2 tracers (Spearman r = 0.5 [ P < 0.01]; Pearson r = 0.4 [ P < 0.01]) in the 221 lesions at baseline. The highest uptake of both tracers was observed in noncalcified lesions, but without any correlation between the tracers (Pearson r = 0.06; P = 0.76). Compared with noncalcified plaques, mildly calcified plaques showed concordant significantly lower accumulation, with good correlation between the tracers (Pearson r = 0.7; P < 0.01). In addition, enhanced osteogenesis-derived 18 F-NaF uptake and regressive inflammation-derived 18 F-FDG uptake were observed in severely calcified lesions (Pearson r = 0.4; P < 0.01). During follow-up, increased calcium density and increased mean 18 F-NaF uptake were observed, whereas mean 18 F-FDG uptake decreased. Most noncalcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified lesions had concordant development of both vascular inflammation and osteogenesis. Conclusion: The combination of 18 F-NaF PET imaging and 18 F

Coronary artery calcification in Kawasaki disease

International Nuclear Information System (INIS)

Ino, T.; Shimazaki, S.; Akimoto, K.; Park, I.; Nishimoto, K.; Yabuta, K.; Tanaka, A.

1990-01-01

To evaluate the angiographic features of coronary lesions in Kawasaki disease with coronary artery calcification, cinefluoroscopy and cineangiography were retrospectively reviewed in 116 patients who had undergone coronary angiography between 1982 and 1989. Angiographic abnormalities of coronary arteries were demonstrated in 55 of 116 patients. In 5 (9.1%) of the 55 patients, 9 with calcification were identified by cinefluoroscopy and chest X-ray. Eight of the 9 calcified lesions showed a circular or ring-shape configuration. Coronary angiography revealed a total occlusion of the right coronary artery with collateral circulation from the distal left coronary artery in 2 patients and a severe stenosis of the right coronary artery in 2 patients, in whom anticoagulant therapy had not been continued during the follow-up periods. The remaining patient in whom anticoagulant therapy had been continued had bilateral aneurysms but no significant stenosis. These results indicate that a ring-shape calcification on chest X-ray in 2 patients with a history of Kawasaki disease may suggest an involvement by coronary artery stenosis even when anticoagulant drugs had been given. Therefore, coronary angiography should be performed to evaluate the stenotic lesions if this type of calcification is found by routine radiographic examination. (orig.)

Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke.

Directory of Open Access Journals (Sweden)

Sverre Holm

Full Text Available BACKGROUND AND PURPOSE: Fatty acid binding protein 4 (FABP4 has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke. METHODS: We examined plasma FABP4 levels in asymptomatic (n = 28 and symptomatic (n = 31 patients with carotid atherosclerosis, as well as in 202 subjects with acute ischemic stroke. In a subgroup of patients we also analysed the expression of FABP4 within the atherosclerotic lesion. In addition, we investigated the ability of different stimuli with relevance to atherosclerosis to regulate FABP4 expression in monocytes/macrophages. RESULTS: FABP4 levels were higher in patients with carotid atherosclerosis, both systemically and within the atherosclerotic lesion, with particular high mRNA levels in carotid plaques from patients with the most recent symptoms. Immunostaining of carotid plaques localized FABP4 to macrophages, while activated platelets and oxidized LDL were potent stimuli for FABP4 expression in monocytes/macrophages in vitro. When measured at the time of acute ischemic stroke, high plasma levels of FABP4 were significantly associated with total and cardiovascular mortality during follow-up, although we did not find that addition of FABP4 to the fully adjusted multivariate model had an effect on the prognostic discrimination for all-cause mortality as assessed by c-statistics. CONCLUSIONS: FABP4 is linked to atherogenesis, plaque instability and adverse outcome in patients with carotid atherosclerosis and acute ischemic stroke.

Double Trouble Foraminiferal Calcification in a Changing Ocean

NARCIS (Netherlands)

Van Dijk, I.E.Y.

2017-01-01

Within the project ‘Double Trouble: Foraminiferal Calcification in a Changing Ocean’, I tried to illuminate mechanisms determining element incorporation in foraminifera with different calcification strategies. In particular, I aimed to assess the interplay between ocean acidification and

Double Trouble : Foraminiferal calcification in a changing ocean

NARCIS (Netherlands)

van Dijk, I.E.Y.

2017-01-01

Within the project ‘Double Trouble: Foraminiferal Calcification in a Changing Ocean’, I tried to illuminate mechanisms determining element incorporation in foraminifera with different calcification strategies. In particular, I aimed to assess the interplay between ocean acidification and

Genetic associations with valvular calcification and aortic stenosis

DEFF Research Database (Denmark)

Thanassoulis, George; Campbell, Catherine Y; Owens, David S

2013-01-01

Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease.......Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease....

Smoking and morphology of calcific deposits affect the outcome of needle aspiration of calcific deposits (NACD) for calcific tendinitis of the rotator cuff.

Science.gov (United States)

Oudelaar, Bart W; Ooms, Edwin M; Huis In 't Veld, Rianne M H A; Schepers-Bok, Relinde; Vochteloo, Anne J

2015-11-01

Although NACD has proven to be an effective minimal invasive treatment for calcific tendinitis of the rotator cuff, little is known about the factors associated with treatment failure or the need for multiple procedures. Patients with symptomatic calcific tendinitis who were treated by NACD were evaluated in a retrospective cohort study. Demographic details, medical history, sonographic and radiographic findings were collected from patient files. Failure of NACD was defined as the persistence of symptoms after a follow-up of at least six months. NACD procedures performed within six months after a previous NACD procedure were considered repeated procedures. Multivariate logistic regression analysis was used to determine factors associated with treatment failure and multiple procedures. 431 patients (277 female; mean age 51.4±9.9 years) were included. Smoking (adjusted odds ratio (AOR): 1.7, 95% CI 1.0-2.7, p=0.04) was significantly associated with failure of NACD. Patients with Gärtner and Heyer (GH) type I calcific deposits were more likely to need multiple NACD procedures (AOR: 3.4, 95% CI 1.6-7.5, protator cuff tears were of no influence on the outcome of NACD or the number of treatments necessary. Smoking almost doubled the chance of failure of NACD and the presence of GH type I calcific deposits significantly increased the chance of multiple procedures. Partial thickness rotator cuff tears did not seem to affect the outcome of NACD. Based on the findings in this study, the importance of quitting smoking should be emphasized prior to NACD and partial thickness rotator cuff tears should not be a reason to withhold patients NACD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Left ventricular calcification following postpartum toxic shock syndrome

Directory of Open Access Journals (Sweden)

Stella C Pak

2018-01-01

Full Text Available Toxic shock syndrome (TSS is a rare but lethal clinical event that can occur during the postpartum period. Early recognition and intervention is critical to improve patient outcomes. This is a case of TSS complicated by cardiac arrest and left ventricular calcification. This is a case report of streptococcal TSS in a 29-year-old female in the postpartum period who presented with fever, abdominal distension, and a purpuric rash. Her hospital course was characterized by multiple organ failure, including respiratory distress syndrome, liver failure, renal failure, and coagulopathy. She was found to have acute compartment syndrome, which resulted in a below-the-knee amputation. She deteriorated further after experiencing cardiac arrest and the development of hypoxic-ischemic encephalopathy with hemorrhagic transformation. A computed tomography scan of the chest revealed evidence of dystrophic myocardial calcification in the left ventricle. She improved clinically but remained ventilator dependent upon discharge to an extended acute care facility. Sepsis-induced cardiomyopathy can result in myocardial calcification. As dystrophic calcification can significantly affect cardiac function, clinicians should rule out cardiac calcification in patients who have had severe septic shock.

Coffee Consumption and Coronary Calcification: The Rotterdam Coronary Calcification Study

NARCIS (Netherlands)

Woudenbergh, van G.J.; Vliegenthart, R.; Rooij, van F.J.A.; Hofman, A.; Oudkerk, M.; Witteman, J.C.M.; Geleijnse, J.M.

2008-01-01

Background¿ The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. Methods and Results¿ The study involved 1570 older men and women without coronary heart disease who participated in the

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: a cross-sectional study.

Science.gov (United States)

Zheng, T P; Liu, Y H; Yang, L X; Qin, S H; Liu, H B

2015-10-01

Hyperglycemia, insulin resistance, dislipidemia, oxidative stress and inflammation are well-documented risk factors for subclinical atherosclerosis. Dipeptidyl peptidase-4(DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and subclinical atherosclerosis in type 2 diabetes. A total of 985 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor (M6P-R), oxidative stress parameters, inflammatory markers and common carotid artery Intima-Media Thickness (c-IMT) were measured in all participants. Participants in the highest quartile of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin resistance(HOMA-IR), triglyceride, low-density lipoprotein cholesterol(LDL-C), oxidized LDL, nitrotyrosine, 8-iso-PGF2a, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), M6P-R, c-IMT compared with participants in the lowest quartile (all P dislipidemia, oxidative stress and inflammation were higher with increasing DPP4 quartiles (P < 0.001 for trend). In the highest DPP4 quartile, subclinical atherosclerosis risk was significantly higher (OR 4.97; 95% CI 3.03-8.17) than in the lowest quartile. This association remained strong (2.17; 1.21-3.89) after further controlling for HbA1c, HOMA-IR, triglyceride, oxidized LDL, nitrotyrosine, and IL-6. This study shows that increased DPP4 activities are positively and independently associated with subclinical atherosclerosis in type 2 diabetes. Our findings suggest of potential role of DPP4 in the pathogenesis of subclinical atherosclerosis and in the prevention and management of this disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Calcific myonecrosis: keys to early recognition

International Nuclear Information System (INIS)

Holobinko, Newt J.; Scerpella, Patrick R.; Hojnowski, Leonard; Damron, Timothy A.

2003-01-01

Calcific myonecrosis is a rare, late sequela of trauma occurring almost exclusively in the lower extremity which may be confused with an aggressive primary neoplasm. The platelike mineralization pattern seen on radiographs is characteristic but not widely recognized by clinicians. Three cases of calcific myonecrosis are reported, unique in that two presented for care following infection and that one had extended to involve the muscle compartments of the foot, a previously unreported site. (orig.)

Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

OpenAIRE

Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

2015-01-01

Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr’s disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly present...

Idiopathic Pulmonary Calcification and Ossification in an Elderly ...

African Journals Online (AJOL)

Histology of tissue from autopsy showed intraparenchymal pulmonary calcification and ossification with marrow elements. Idiopathic pulmonary calcification and ossification is rare. At autopsy, she was also found to have had bilateral subarachnoid haemorrhage (SAH), a diagnosis missed during clinical evaluation.

The association between dietary cholesterol intake and subclinical atherosclerosis in Korean adults: The Kangbuk Samsung Health Study.

Science.gov (United States)

Rhee, Eun-Jung; Ryu, Seungho; Lee, Jong-Young; Lee, Sung Ho; Cheong, EunSun; Park, Se Eun; Park, Cheol-Young; Won, Yu Sam; Kim, Joon Mo; Cho, Dong-Sik; Chung, Hye-Kyung; Sung, Ki Chul

The Scientific Report of the Dietary Guidelines Advisory Committee (2015) concluded that restriction of dietary cholesterol is unnecessary in most adults for the prevention of cardiovascular disease. We aimed to assess the risk for subclinical atherosclerosis according to coronary artery calcium score (CACS), based on dietary cholesterol intake in apparently healthy Korean adults. This was a cross-sectional study performed in 30,068 participants (mean age 40.8 years; 84.5% men) in a health screening program in Korea. The data were collected from 2001 to 2013 and analyzed in 2015. Total energy intake and dietary cholesterol intake were assessed with a food frequency questionnaire. The participants were stratified according to quartile of dietary cholesterol intake. CACS was measured by multi-detector computed tomography. Lipid profiles were measured, and the participants were divided into 6 groups according to low-density lipoprotein cholesterol (LDL-C) level: 0. Dietary cholesterol intake did not correlate with mean value of serum LDL-C level. For both genders, the odds ratio for coronary artery calcification was not significantly greater with greater amounts of dietary cholesterol (as assessed by quartile). The risk for coronary artery calcification was not higher in subjects with LDL-C 70-129 mg/dL compared with those with LDL-C < 70 mg/dL; however, the risk was significantly greater in subjects with LDL-C ≥ 130 mg/dL compared with those with LDL-C < 70 mg/dL. Dietary cholesterol intake did not have an association with LDL-C level or with risk for coronary artery calcification in apparently healthy Korean adults. The results have to be translated with consideration of limitation of population-based studies. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Histological Characteristics of Intracranial Atherosclerosis in a Chinese Population: A Postmortem Study

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Wen Jie Yang

2017-09-01

Full Text Available BackgroundAnterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature.MethodsIntracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs (both left and right, vertebral arteries (VAs (side more affected, and basilar arteries (BAs.ResultsProgressive atherosclerotic lesions were present in 91(71% of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 ± 25 vs. 30 ± 24 vs. 20 ± 20%, all p < 0.05. MCA had more eccentric (vs. concentric plaques than VA (69 vs. 25%, p = 0.003 and BA (69 vs. 38%; p = 0.03. Lumen thrombi were more frequent in BA, and calcification most commonly occurred in VA atherosclerotic lesions.ConclusionIntracranial atherosclerotic plaques were commonly present in this sample, but the lesions generally lacked features of complicated plaques. MCA lesions had demonstrable differences compared with VA and BA lesions. Further studies are needed to determine whether these characteristics indicate a distinctive atherosclerotic phenotype for the intracranial vasculature.

Prevalence of Soft Tissue Calcifications in CBCT Images of Mandibular Region.

Science.gov (United States)

Khojastepour, Leila; Haghnegahdar, Abdolaziz; Sayar, Hamed

2017-06-01

Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p < 0.05 was considered to be statistically significant. 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group.

Thymic Stromal Lymphopoietin Attenuates the Development of Atherosclerosis in ApoE−/− Mice

Science.gov (United States)

Yu, Kunwu; Zhu, Pengfei; Dong, Qian; Zhong, Yucheng; Zhu, Zhengfeng; Lin, Yingzhong; Huang, Ying; Meng, Kai; Ji, Qingwei; Yi, Guiwen; Zhang, Wei; Wu, Bangwei; Mao, Yi; Cheng, Peng; Zhao, Xiaoqi; Mao, Xiaobo; Zeng, Qiutang

2013-01-01

Background Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown. Methods and Results In vitro, we examined the phenotype of TSLP‐conditioned bone marrow dendritic cells (TSLP‐DCs) of apolipoprotein E–deficient (ApoE−/−) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP‐DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency‐associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP‐DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE−/− mice, and TSLP administration increased the levels of antioxidized low‐density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP‐DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti‐TGF‐β antibody. Conclusions Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis. PMID:23985377

Loss of function of Slc20a2 associated with familial idiopathic Basal Ganglia calcification in humans causes brain calcifications in mice

DEFF Research Database (Denmark)

Jensen, N.; Schroder, H. D.; Hejbol, E. K.

2013-01-01

Familial idiopathic basal ganglia calcification (FIBGC) is a neurodegenerative disorder with neuropsychiatric and motor symptoms. Deleterious mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), were recently linked to FIBGC in almost 50% of the families...... reported worldwide. Here, we show that knockout of Slc20a2 in mice causes calcifications in the thalamus, basal ganglia, and cortex, demonstrating that reduced PiT2 expression alone can cause brain calcifications....

Endothelial Lipase Concentrations Are Increased in Metabolic Syndrome and Associated with Coronary Atherosclerosis.

Directory of Open Access Journals (Sweden)

2005-12-01

Full Text Available BACKGROUND: Endothelial lipase (EL, a new member of the lipase family, has been shown to modulate high-density lipoprotein (HDL-C metabolism and atherosclerosis in mouse models. We hypothesized that EL concentrations would be associated with decreased HDL-C and increased atherosclerosis in humans. METHODS AND FINDINGS: Healthy individuals with a family history of premature coronary heart disease (n = 858 were recruited as part of the Study of the Inherited Risk of Atherosclerosis. Blood was drawn in the fasting state before and, in a subgroup (n = 510, after administration of a single dose of intravenous heparin. Plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (CAC was quantified by electron beam computed tomography. Plasma EL mass was measured using a newly developed enzyme-linked immunosorbent assay. Median EL mass in pre-heparin plasma was 442 (interquartile range = 324-617 ng/ml. Median post-heparin mass was approximately 3-fold higher, 1,313 (888-1,927 ng/ml. The correlation between pre-heparin EL mass and post-heparin EL mass was 0.46 (p < 0.001. EL mass concentrations in both pre- and post-heparin plasma significantly correlated with all NCEP ATPIII-defined metabolic syndrome factors: waist circumference (r = 0.28 and 0.22, respectively, p < 0.001 for each, blood pressure (r = 0.18 and 0.24, p < 0.001 for each, triglycerides (r = 0.22, p < 0.001; and 0.13, p = 0.004, HDL cholesterol (r = -0.11, p = 0.002; and -0.18, p < 0.001, and fasting glucose (r = 0.11 and 0.16, p = 0.001 for both. EL mass in both routine (odds ratio [OR] = 1.67, p = 0.01 and post-heparin (OR = 2.42, p = 0.003 plasma was associated with CAC as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women, and established cardiovascular risk factors. CONCLUSIONS: We report, to our knowledge

Cyanotic congenital heart disease and atherosclerosis.

Science.gov (United States)

Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

2017-06-01

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Atherosclerosis and atherosensitivity in two southwest Algerian desert rodents, Psammomys obesus and Gerbillus gerbillus, and in Rattus norvegicus

Directory of Open Access Journals (Sweden)

El-Aoufi S

2012-09-01

Full Text Available Salima El-Aoufi,1 Mohamed-Amine Lazourgui,1 Lakhdar Griene,2 Boubekeur Maouche31Laboratoire de Biologie et de Physiologie des Organismes/MMDED, Faculté des Sciences Biologiques, USTHB, El-Alia, Dar El Beida, Algeria; 2Laboratoire d'Hormonologie, Centre Pierre et Marie Curie, C.H.U Mustapha, Algeria; 3Laboratoire de Physicochimie Théorique et Chimie Informatique, Faculté de Chimie, USTHB, El-Alia, Dar El Beida, AlgeriaAbstract: Cardiovascular disease, including atherosclerosis, is the leading cause of death in patients with diabetes worldwide; thus, it is a major medical concern. The endothelium contributes to the control of many vascular functions, and clinical observations show that it is a primary target for diabetic syndrome. To get better insight into the mechanisms underlying atherosclerosis, we studied the interspecific differences in the arterial metabolisms of two, Psammomys obesus and Gerbillus gerbillus, as well as Rattus norvegicus (Wistar rat, well known for its atheroresistance. Twenty-two enzymatic activities and six macromolecular substances were histochemically compared in the two desert species and in Wistar aortas (abdominal and thoracic and arteries (femoral and caudal embedded in a common block. In the healthy adult rodents, enzyme activities were very intense. They demonstrated that aortic myocytes are capable of various synthesis and catabolism processes. However, considering the frequency of atherosclerosis and its phenotypes, significant differences appeared between the species studied. Our comparative study shows that aortic atherosensitive animals have several common metabolic characteristics, which are found in Psammomys rich in metachromatic glycosaminoglycans (involved in the inhibition of lipolysis and in calcification of the organic matrix, reduced activity in enzymes related to the Krebs cycle (weakening energetic power, and low lipolytic enzyme, adenosine triphosphatase, and adenosine diphosphatase activities

Asymptomatic ''crowned dens'' calcification in CT images for the craniovertebral junction

International Nuclear Information System (INIS)

Kubota, Gen; Mori, Masataka; Fukushima, Tatsuro

2007-01-01

Calcification around the odontoid process suggests 'crowned dens' syndrome, when accompanied with acute occipital headache or neck pain and with inflammatory signs. We retrospectively searched for calcification around the odontoid process in routine CT images of 282 patients emcompassing the craniovertebral junction, and found 13 (4.6%) had 'crowned dens' calcifications with neither characteristic symptoms nor signs suggestive for crowned dens' syndrome. Females of older ages frequently showed asymptomatic crowned dens' calcifications. (author)

Heart failure due to severe myocardial calcification

International Nuclear Information System (INIS)

Takahashi, Shouichi; Maida, Kiyoshi; Yokoyama, Hitoshi; Tanaka, Shigeo

1993-01-01

A 28-year-old female who had had irradiation on the chest wall at the age of 5 as a remedy for keloid granulation after burn, recently developed congestive heart failure. Severe tricuspid regurgitation was demonstrated by echocardiography with a certain calcification in the cardiac shadow on chest radiogram. Calcified right ventricle and ventricular septum were noticed operatively, which disturbed ventricular motion and also caused tricuspid valve deformity. These calcified myocardium apparently corresponded with the irradiation field. After tricuspid valve replacement, she regained physical activity satisfactorily without congestive heart failure. Because she had no other known causes of cardiac calcification such as hypercalcemia, myocarditis, myocardial infarction or renal diseases, irradiation on the chest wall could be responsible for the severe myocardial calcification. (author)

Clinicoradiologic evaluation of styloid process calcification

International Nuclear Information System (INIS)

Bagga, Mun Bhawni; Kumar, C. Anand; Yeluri, Garima

2012-01-01

This study was performed to investigate the prevalence, morphology, and calcification pattern of the elongated styloid process in the Mathura population and its relation to gender, age, and mandibular movements. The study analyzed digital panoramic radiographs of 2,706 adults. The elongated styloid process was classified with the radiographic appearance based on the morphology and calcification pattern. The limits of mandibular protrusion were evaluated for each subject. The data were analyzed by using a Student's t-test and chi-squared test with significance set at p=0.05. Bilateral elongation having an 'elongated' type styloid process with a 'partially mineralized' pattern was the most frequent type of styloid process. No correlation was found between styloid process type and calcification pattern on the one hand and gender on the other, although elongated styloid was more prevalent in older and male populations (p 0.05). Dentists should recognize the existence of morphological variation in elongated styloid process or Eagle syndrome apparent on panoramic radiographs. We found higher prevalence of elongated styloid process in the population of the Mathura region when compared with other Indian populations. The calcification of the styloid process was more common in the older age group with no correlation to gender, mandibular movement and site. 'Type I' with a 'partially calcified' styloid process was observed more frequently in the population studied.

Recurrent acute low back pain secondary to lumbar epidural calcification

Energy Technology Data Exchange (ETDEWEB)

Ziade, M.; Zufferey, P.; So, A.K.L. [Centre Hospitalier Vaudois, Service de Rhumatologie, Lausanne (Switzerland)

2007-06-15

Epidural calcification is a rare cause of back pain, and spontaneous epidural calcification has not been reported previously. We describe a patient with acute low back pain and signs of lumbar nerve root compression due to epidural calcification, as demonstrated by CT-scan and MRI. Radiological signs of spondylodiscitis led to a search for an infectious cause, which was negative, and her symptoms responded rapidly to NSAID treatment alone. Her symptoms recurred 18 months later, and further imaging studies again revealed epidural calcification, but with a changed distribution. Her symptoms were relieved once more by NSAID treatment alone. We propose that epidural calcification secondary to aseptic spondylodiscitis is the main cause of acute back pain in this patient. A possible mechanism may be the pro-inflammatory effects of calcium pyrophosphate or hydroxyapatite crystal deposition within the epidural space. (orig.)

Recurrent acute low back pain secondary to lumbar epidural calcification

International Nuclear Information System (INIS)

Ziade, M.; Zufferey, P.; So, A.K.L.

2007-01-01

Epidural calcification is a rare cause of back pain, and spontaneous epidural calcification has not been reported previously. We describe a patient with acute low back pain and signs of lumbar nerve root compression due to epidural calcification, as demonstrated by CT-scan and MRI. Radiological signs of spondylodiscitis led to a search for an infectious cause, which was negative, and her symptoms responded rapidly to NSAID treatment alone. Her symptoms recurred 18 months later, and further imaging studies again revealed epidural calcification, but with a changed distribution. Her symptoms were relieved once more by NSAID treatment alone. We propose that epidural calcification secondary to aseptic spondylodiscitis is the main cause of acute back pain in this patient. A possible mechanism may be the pro-inflammatory effects of calcium pyrophosphate or hydroxyapatite crystal deposition within the epidural space. (orig.)

Calcification remodeling index characterized by cardiac CT as A novel parameter to predict the use of rotational atherectomy for coronary intervention of lesions with moderate to severe calcification

International Nuclear Information System (INIS)

Yu, Meng Meng; Li, Yue Hua; Li, Wen Bin; Lu, Zhi Gang; Wei, Meng; Zhang, Jia Yin

2017-01-01

To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation.

Calcification Remodeling Index Characterized by Cardiac CT as a Novel Parameter to Predict the Use of Rotational Atherectomy for Coronary Intervention of Lesions with Moderate to Severe Calcification

Science.gov (United States)

Yu, Mengmeng; Li, Yuehua; Li, Wenbin; Lu, Zhigang; Wei, Meng

2017-01-01

Objective To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Materials and Methods Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. Results A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Conclusion Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation. PMID:28860893

Calcification remodeling index characterized by cardiac CT as A novel parameter to predict the use of rotational atherectomy for coronary intervention of lesions with moderate to severe calcification

Energy Technology Data Exchange (ETDEWEB)

Yu, Meng Meng; Li, Yue Hua; Li, Wen Bin; Lu, Zhi Gang; Wei, Meng; Zhang, Jia Yin [Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai (China)

2017-09-15

To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation.

Abdominal aortic calcification in dialysis patients: results of the CORD study

DEFF Research Database (Denmark)

Honkanen, Eero; Kauppila, Leena; Wikström, Björn

2008-01-01

BACKGROUND: Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain...

Impact of seawater carbonate chemistry on the calcification of marine bivalves

Science.gov (United States)

Thomsen, J.; Haynert, K.; Wegner, K. M.; Melzner, F.

2015-07-01

Bivalve calcification, particularly of the early larval stages, is highly sensitive to the change in ocean carbonate chemistry resulting from atmospheric CO2 uptake. Earlier studies suggested that declining seawater [CO32-] and thereby lowered carbonate saturation affect shell production. However, disturbances of physiological processes such as acid-base regulation by adverse seawater pCO2 and pH can affect calcification in a secondary fashion. In order to determine the exact carbonate system component by which growth and calcification are affected it is necessary to utilize more complex carbonate chemistry manipulations. As single factors, pCO2 had no effects and [HCO3-] and pH had only limited effects on shell growth, while lowered [CO32-] strongly impacted calcification. Dissolved inorganic carbon (CT) limiting conditions led to strong reductions in calcification, despite high [CO32-], indicating that [HCO3-] rather than [CO32-] is the inorganic carbon source utilized for calcification by mytilid mussels. However, as the ratio [HCO3-] / [H+] is linearly correlated with [CO32-] it is not possible to differentiate between these under natural seawater conditions. An equivalent of about 80 μmol kg-1 [CO32-] is required to saturate inorganic carbon supply for calcification in bivalves. Below this threshold biomineralization rates rapidly decline. A comparison of literature data available for larvae and juvenile mussels and oysters originating from habitats differing substantially with respect to prevailing carbonate chemistry conditions revealed similar response curves. This suggests that the mechanisms which determine sensitivity of calcification in this group are highly conserved. The higher sensitivity of larval calcification seems to primarily result from the much higher relative calcification rates in early life stages. In order to reveal and understand the mechanisms that limit or facilitate adaptation to future ocean acidification, it is necessary to better

Size-dependent response of foraminiferal calcification to seawater carbonate chemistry

Science.gov (United States)

Henehan, Michael J.; Evans, David; Shankle, Madison; Burke, Janet E.; Foster, Gavin L.; Anagnostou, Eleni; Chalk, Thomas B.; Stewart, Joseph A.; Alt, Claudia H. S.; Durrant, Joseph; Hull, Pincelli M.

2017-07-01

The response of the marine carbon cycle to changes in atmospheric CO2 concentrations will be determined, in part, by the relative response of calcifying and non-calcifying organisms to global change. Planktonic foraminifera are responsible for a quarter or more of global carbonate production, therefore understanding the sensitivity of calcification in these organisms to environmental change is critical. Despite this, there remains little consensus as to whether, or to what extent, chemical and physical factors affect foraminiferal calcification. To address this, we directly test the effect of multiple controls on calcification in culture experiments and core-top measurements of Globigerinoides ruber. We find that two factors, body size and the carbonate system, strongly influence calcification intensity in life, but that exposure to corrosive bottom waters can overprint this signal post mortem. Using a simple model for the addition of calcite through ontogeny, we show that variable body size between and within datasets could complicate studies that examine environmental controls on foraminiferal shell weight. In addition, we suggest that size could ultimately play a role in determining whether calcification will increase or decrease with acidification. Our models highlight that knowledge of the specific morphological and physiological mechanisms driving ontogenetic change in calcification in different species will be critical in predicting the response of foraminiferal calcification to future change in atmospheric pCO2.

Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

Energy Technology Data Exchange (ETDEWEB)

Karimi, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Hematology Research Center, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: karimim@sums.ac.ir; Rasekhi, A.R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: rasekhia@sums.ac.ir; Rasekh, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: Rasekhm@sums.ac.ir; Nabavizadeh, S.A. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: nabavia@gmail.com; Assadsangabi, R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: assadsangabi@yahoo.com; Amirhakimi, G.H. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: amirhakimig@sums.ac.ir

2009-06-15

Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

International Nuclear Information System (INIS)

Karimi, M.; Rasekhi, A.R.; Rasekh, M.; Nabavizadeh, S.A.; Assadsangabi, R.; Amirhakimi, G.H.

2009-01-01

Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

Can dental pulp calcification predict the risk of ischemic cardiovascular disease?

Science.gov (United States)

Khojastepour, Leila; Bronoosh, Pegah; Khosropanah, Shahdad; Rahimi, Elham

2013-09-01

To report the association of pulp calcification with that of cardiovascular disease (CVD) using digital panoramic dental radiographs. Digital panoramic radiographs of patients referred from the angiography department were included if the patient was under 55 years old and had non-restored or minimally restored molars and canines. An oral and maxillofacial radiologist evaluated the images for pulpal calcifications in the selected teeth. The sensitivity, specificity, positive predictive value and negative predictive value of panoramic radiography in predicting CVD were calculated. Out of 122 patients who met the criteria, 68.2% of the patients with CVD had pulp chamber calcifications. Pulp calcification in panoramic radiography had a sensitivity of 68.9% to predict CVD. This study demonstrates that patients with CVD show an increased incidence of pulp calcification compared with healthy patients. The findings suggest that pulp calcification on panoramic radiography may have possibilities for use in CVD screening.

The association of breast arterial calcification and metabolic syndrome

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Seyma Yildiz

2014-01-01

Full Text Available OBJECTIVES: We investigated the relationship between metabolic syndrome and breast arterial calcification detected via mammography in a cohort of postmenopausal subjects. METHODS: Among 837 patients referred to our radiology department for mammographic screening, 310 postmenopausal females (105 patients with and 205 patients without breast arterial calcification aged 40 to 73 (mean 55.9±8.4 years were included in this study. The groups were compared with respect to clinical characteristics and metabolic syndrome criteria. Univariate and multivariate analyses identified the factors related to breast arterial calcification. RESULTS: Age, postmenopausal duration and the frequencies of diabetes mellitus, hypertension and metabolic syndrome were significantly higher in the subjects with breast arterial calcification than in those without (p<0.05. Multivariate analysis indicated that age (OR = 1.3, 95% CI = 1.1-1.6, p = 0.001 and metabolic syndrome (OR = 4.0, 95% CI = 1.5−10.4, p = 0.005 were independent predictors of breast arterial calcification detected via mammography. The independent predictors among the features of metabolic syndrome were low levels of high-density lipoproteins (OR = 8.1, 95% CI = 1.0−64.0, p = 0.047 and high blood pressure (OR = 8.7, 95% CI = 1.5−49.7, p = 0.014. CONCLUSIONS: The likelihood of mammographic detection of breast arterial calcification increases with age and in the presence of hypertension or metabolic syndrome. For patients undergoing screening mammography who present with breast arterial calcification, the possibility of metabolic syndrome should be considered. These patients should be informed of their cardiovascular risk factors and counseled on appropriate lifestyle changes.

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.

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Hernández, Domingo; Triñanes, Javier; Armas, Ana María; Ruiz-Esteban, Pedro; Alonso-Titos, Juana; Duarte, Ana; González-Molina, Miguel; Palma, Eulalia; Salido, Eduardo; Torres, Armando

2017-07-01

Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin-angiotensin system could contribute to this vascular damage. Thus, understanding the vascular lesions that occur in KT recipients and the pathogenic mechanisms involved in their development could be crucial to optimize the therapeutic management and outcomes in survival of this population. This review focuses on the following issues: (1) epidemiological data framing the problem; (2) atheromatosis in KT patients: subclinical and clinical atheromatosis, involving ischemic heart disease, congestive heart failure, stroke and peripheral vascular disease; (3) arteriosclerosis and vascular calcifications; and (4) potential pathogenic mechanisms and their therapeutic targets. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Foraminiferal calcification and CO2

Science.gov (United States)

Nooijer, L. D.; Toyofuku, T.; Reichart, G. J.

2017-12-01

Ongoing burning of fossil fuels increases atmospheric CO2, elevates marine dissolved CO2 and decreases pH and the saturation state with respect to calcium carbonate. Intuitively this should decrease the ability of CaCO3-producing organisms to build their skeletons and shells. Whereas on geological time scales weathering and carbonate deposition removes carbon from the geo-biosphere, on time scales up to thousands of years, carbonate precipitation increases pCO2 because of the associated shift in seawater carbon speciation. Hence reduced calcification provides a potentially important negative feedback on increased pCO2 levels. Here we show that foraminifera form their calcium carbonate by active proton pumping. This elevates the internal pH and acidifies the direct foraminiferal surrounding. This also creates a strong pCO2 gradient and facilitates the uptake of DIC in the form of carbon dioxide. This finding uncouples saturation state from calcification and predicts that the added carbon due to ocean acidification will promote calcification by these organisms. This unknown effect could add substantially to atmospheric pCO2 levels, and might need to be accounted for in future mitigation strategies.

Can Dental Pulp Calcification Predict the Risk of Ischemic Cardiovascular Disease?

Directory of Open Access Journals (Sweden)

Leila Khojastepour

2013-01-01

Full Text Available Objective: To report the association of pulp calcification with that of cardiovascular disease (CVD using digital panoramic dental radiographs.Materials and Methods: Digital panoramic radiographs of patients referred from the angiography department were included if the patient was under 55 years old and had non-restored or minimally restored molars and canines. An oral and maxillofacial radiologist evaluated the images for pulpal calcifications in the selected teeth. The sensitivity, specificity, positive predictive value and negative predictive value of panoramic radiography in predicting CVD were calculated.Results: Out of 122 patients who met the criteria, 68.2% of the patients with CVD had pulp chamber calcifications. Pulp calcification in panoramic radiography had a sensitivity of 68.9% to predict CVD.Conclusion: This study demonstrates that patients with CVD show an increased incidence of pulp calcification compared with healthy patients. The findings suggest that pulp calcification on panoramic radiography may have possibilities for use in CVD screening.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

Science.gov (United States)

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

National Coral Reef Monitoring Program: Calcification Rates of Crustose Coralline Algae Derived from Calcification Accretion Units (CAUs) Deployed across Marianas Archipelago in 2011

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Calcification accretion units, or CAUs, are used to assess the current effects of changes in seawater carbonate chemistry on calcification and accretion rates of...

National Coral Reef Monitoring Program: Calcification Rates of Crustose Coralline Algae Derived from Calcification Accretion Units (CAUs) Deployed across American Samoa in 2012

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Calcification accretion units, or CAUs, are used to assess the current effects of changes in seawater carbonate chemistry on calcification and accretion rates of...

Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

Directory of Open Access Journals (Sweden)

Dipti Deshpande

Full Text Available Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/- mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung Health Study.

Science.gov (United States)

Lee, Min-Kyung; Park, Hye-Jeong; Jeon, Won Seon; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

2015-07-15

It is uncertain whether non-alcoholic fatty liver disease (NAFLD) or abdominal obesity is more associated with atherosclerosis. The aim of this study was to determine whether NAFLD or abdominal obesity is more strongly associated with subclinical atherosclerosis represented by coronary artery calcification (CAC). A total of 21,335 male participants in a health screening program (mean age 41 years) were enrolled. Ultrasonographic measurements of fatty liver and multi-detector computed tomography were performed to determine the coronary artery calcium score (CACS). The presence of CAC was defined as CACS > 0. Subjects were divided into four groups according to the presence or absence of NAFLD and/or abdominal obesity as assessed by waist-hip ratio (WHR) > 0.9. The presence of CAC was detected in 2,385 subjects (11.2%). The proportion of subjects with CAC was highest in the abdominal obesity only group (23.2%). After adjustment for age, diabetes history, hypertension, cigarette smoking, and physical inactivity, the odds ratio (OR) for CAC was the highest in the group with both abnormalities [1.465 (1.324-1.623)]. The NAFLD only group showed significantly increased OR for CAC compared to that in the abdominal obesity only group [1.286 (1.151-1.436) vs. 1.076 (0.939-1.233)]. Non-alcoholic fatty liver disease is more closely associated with CAC than abdominal obesity as assessed by the WHR. NAFLD could be considered an independent determinant of subclinical atherosclerosis as assessed by CAC.

Relationship between intracranial internal carotid artery calcification and enlarged cerebral perivascular space

Energy Technology Data Exchange (ETDEWEB)

Tao, Xiao-Xiao [Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Department of Neurology, Shanghai (China); The First People' s Hospital of Wenling, Department of Neurology, Wenling (China); Li, Ge-Fei; Wu, Yi-Lan; Liu, Yi-Sheng; Zhao, Ying; Shi, Yan-Hui; Zhuang, Mei-Ting; Hou, Tian-Yu; Zhao, Rong; Liu, Feng-Di; Wang, Xue-Mei; Shen, Ying; Cui, Guo-Hong; Su, Jing-Jing; Chen, Wei [Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Department of Neurology, Shanghai (China); Tang, Xue-Mei; Sun, Ji; Liu, Jian-Ren [Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Department of Neurology, Shanghai (China); Shanghai Jiao Tong University School of Medicine, Clinical Research Center, Shanghai (China)

2017-06-15

The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS. (orig.)

Kaempferol and inflammation: From chemistry to medicine.

Science.gov (United States)

Devi, Kasi Pandima; Malar, Dicson Sheeja; Nabavi, Seyed Fazel; Sureda, Antoni; Xiao, Jianbo; Nabavi, Seyed Mohammad; Daglia, Maria

2015-09-01

Inflammation is an important process of human healing response, wherein the tissues respond to injuries induced by many agents including pathogens. It is characterized by pain, redness and heat in the injured tissues. Chronic inflammation seems to be associated with different types of diseases such as arthritis, allergies, atherosclerosis, and even cancer. In recent years natural product based drugs are considered as the novel therapeutic strategy for prevention and treatment of inflammatory diseases. Among the different types of phyto-constituents present in natural products, flavonoids which occur in many vegetable foods and herbal medicines are considered as the most active constituent, which has the potency to ameliorate inflammation under both in vitro and in vivo conditions. Kaempferol is a natural flavonol present in different plant species, which has been described to possess potent anti-inflammatory properties. Despite the voluminous literature on the anti-inflammatory effects of kaempferol, only very limited review articles has been published on this topic. Hence the present review is aimed to provide a critical overview on the anti-inflammatory effects and the mechanisms of action of kaempferol, based on the current scientific literature. In addition, emphasis is also given on the chemistry, natural sources, bioavailability and toxicity of kaempferol. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Placental atherosclerosis and markers of endothelial dysfunction in infants born to mothers with gestational diabetes].

Science.gov (United States)

López Morales, Cruz Mónica; Brito Zurita, Olga Rosa; González Heredia, Ricardo; Cruz López, Miguel; Méndez Padrón, Araceli; Matute Briseño, Juan Antonio

2016-08-05

The pathophysiology of gestational diabetes itself causes hyperstimulation of adipose tissue and of the placenta cells increasing the production of inflammatory cytokines, which cause changes in the tissues exposed such as the placenta and foetus. Therefore, the objective of this study was to compare metabolic markers and endothelial dysfunction in umbilical cord blood, as well as to determine the presence of atherosclerosis in the placentas of newborn infants of patients with gestational diabetes and in patients with normally progressing pregnancies. An analytical cross-sectional study was carried out in 84 patients, obtaining data such as age, smoking and weight gain in pregnancy; the gestational age of the newborns was determined by Capurro, and their weight and destination subsequent to birth, the placentas were also collected in order to look for atherosclerosis through histological studies and glucose, insulin, VLDL-C, HDL-C, triglycerides, cholesterol, fibrinogen, PCR and markers of endothelial dysfunction (adiponectin, VCAM-1, ICAM-1 and IL-6) were determined in blood samples obtained from the umbilical cord. Placental atherosclerosis presented in 28.94% of the group with gestational diabetes compared to 10.52% of the group with normally progressing pregnancies (P=.044); differences were found in glucose, cholesterol, triglycerides, fibrinogen, HOMA-IR, PCR-us, HDL-C, not in VLDL-C. Twenty-one point five percent of the newborns of the gestational diabetes patients required hospitalization, against 5.2% in the control group, Pregnancies that involve diabetes have higher proportion of atherosclerosis, hospitalization of the newborn, insulin resistance, as well as elevation of markers associated with inflammation and endothelial dysfunction in umbilical cord blood. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes.

LENUS (Irish Health Repository)

O'Sullivan, Eoin P

2010-09-01

Osteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor-alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well-established biomarkers of subclinical vascular inflammation such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have not been described.

History of hot flashes and aortic calcification among postmenopausal women.

Science.gov (United States)

Thurston, Rebecca C; Kuller, Lewis H; Edmundowicz, Daniel; Matthews, Karen A

2010-03-01

Menopausal hot flashes are considered largely a quality-of-life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The aim of this study was to determine whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use were examined in an exploratory fashion. Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during perimenopause and postmenopause, which was initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997-2004. Associations between the number of visits with report of hot flashes, divided by the number of visits attended, and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Among women using hormone therapy, a longer history of reported hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P history of hot flashes and coronary artery calcification. Among postmenopausal women using hormone therapy, a longer history of reported hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women.

Deficiency of ATP-Binding Cassette Transporters A1 and G1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

NARCIS (Netherlands)

Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

2013-01-01

Rationale: Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this

Clinicoradiologic evaluation of styloid process calcification

Energy Technology Data Exchange (ETDEWEB)

Bagga, Mun Bhawni [Dept. of Oral Medicine Diagnosis and Radiology, M.N. D.A.V. Dental College and Hospital, Solan (Korea, Republic of); Kumar, C. Anand; Yeluri, Garima [Dept. of Oral Medicine Diagnosis and Radiology, KD Dental College and Hospital, Mathura (Korea, Republic of)

2012-09-15

This study was performed to investigate the prevalence, morphology, and calcification pattern of the elongated styloid process in the Mathura population and its relation to gender, age, and mandibular movements. The study analyzed digital panoramic radiographs of 2,706 adults. The elongated styloid process was classified with the radiographic appearance based on the morphology and calcification pattern. The limits of mandibular protrusion were evaluated for each subject. The data were analyzed by using a Student's t-test and chi-squared test with significance set at p=0.05. Bilateral elongation having an 'elongated' type styloid process with a 'partially mineralized' pattern was the most frequent type of styloid process. No correlation was found between styloid process type and calcification pattern on the one hand and gender on the other, although elongated styloid was more prevalent in older and male populations (p<0.05). Further styloid process elongation showed no effect on mandibular protrusive movement (p>0.05). Dentists should recognize the existence of morphological variation in elongated styloid process or Eagle syndrome apparent on panoramic radiographs. We found higher prevalence of elongated styloid process in the population of the Mathura region when compared with other Indian populations. The calcification of the styloid process was more common in the older age group with no correlation to gender, mandibular movement and site. 'Type I' with a 'partially calcified' styloid process was observed more frequently in the population studied.

Basal ganglia calcification on computed tomography in systemic lupus erythematosus

International Nuclear Information System (INIS)

Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki

1988-01-01

The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis. (author)

Basal ganglia calcification on computed tomography in systemic lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki and others

1988-09-01

The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis.

Association of aortic valve calcification to the presence, extent, and composition of coronary artery plaque burden: from the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial.

Science.gov (United States)

Mahabadi, Amir A; Bamberg, Fabian; Toepker, Michael; Schlett, Christopher L; Rogers, Ian S; Nagurney, John T; Brady, Thomas J; Hoffmann, Udo; Truong, Quynh A

2009-10-01

Aortic valve calcification (AVC) is associated with cardiovascular risk factors and coronary artery calcification. We sought to determine whether AVC is associated with the presence and extent of overall plaque burden, as well as to plaque composition (calcified, mixed, and noncalcified). We examined 357 subjects (mean age 53 +/- 12 years, 61% male) who underwent contrast-enhanced electrocardiogram-gated 64-slice multidetector computed tomography from the ROMICAT trial for the assessment of presence and extent of coronary plaque burden according to the 17-coronary segment model and presence of AVC. Patients with AVC (n = 37, 10%) were more likely than those without AVC (n = 320, 90%) to have coexisting presence of any coronary plaque (89% vs 46%, P AVC had >3-fold increase odds of having any plaque (adjusted odds ratio [OR] 3.6, P = .047) and an increase of 2.5 segments of plaque (P AVC. When stratified by plaque composition, AVC was associated most with calcified plaque (OR 5.2, P = .004), then mixed plaque (OR 3.2, P = .02), but not with noncalcified plaque (P = .96). Aortic valve calcification is associated with the presence and greater extent of coronary artery plaque burden and may be part of the later stages of the atherosclerosis process, as its relation is strongest with calcified plaque, less with mixed plaque, and nonsignificant with noncalcified plaque. If AVC is present, consideration for aggressive medical therapy may be warranted.

Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

LENUS (Irish Health Repository)

Packard, Chris J

2011-01-17

Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father\\'s occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father\\'s occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the \\'health divide\\' requires that these life course determinants are taken into account.

Context-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation.

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Miller, Yury I; Shyy, John Y-J

2017-02-01

Oxidized low-density lipoprotein (OxLDL), which contains hundreds of different oxidized lipid molecules, is a hallmark of hyperlipidemia and atherosclerosis. The same oxidized lipids found in OxLDL are also formed in apoptotic cells, and are present in tissues as well as in the circulation under pathological conditions. In many disease contexts, oxidized lipids constitute damage signals, or patterns, that activate pattern-recognition receptors (PRRs) and significantly contribute to inflammation. Here, we review recent discoveries and emerging trends in the field of oxidized lipids and the regulation of inflammation, focusing on oxidation products of polyunsaturated fatty acids esterified into cholesteryl esters (CEs) and phospholipids (PLs). We also highlight context-dependent activation and biased agonism of Toll-like receptor-4 (TLR4) and the NLRP3 inflammasome, among other signaling pathways activated by oxidized lipids. Copyright © 2016 Elsevier Ltd. All rights reserved.

Warfarin accelerated vascular calcification and worsened cardiac dysfunction in remnant kidney mice

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Ming-Tsun Tsai

2018-04-01

Full Text Available Background: Vascular calcification is highly prevalent in end-stage renal disease (ESRD and is a significant risk factor for future cardiovascular events and death. Warfarin use results in dysfunction of matrix Gla protein, an inhibitor of vascular calcification. However, the effect of warfarin on vascular calcification in patients with ESRD is still not well characterized. Thus we investigated whether arterial calcification can be accelerated by warfarin treatment both in vitro and in vivo using a mouse remnant kidney model. Methods: Human aortic smooth muscle cells (HASMC were cultured in medium supplemented with warfarin and phosphate to investigate the potential role of this drug in osteoblast transdifferentiation. For in vivo study, adult male C57BL/6 mice underwent 5/6 nephrectomy were treated with active vitamin D3 plus warfarin to determine the extent of vascular calcification and parameters of cardiovascular function. Results: We found that the expressions of Runx2 and osteocalcin in HASMC were markedly enhanced in the culture medium containing warfarin and high phosphate concentration. Warfarin induced calcification of cultured HASMC in the presence of high phosphate levels, and this effect is inhibited by vitamin K2. Severe aortic calcification and reduced left ventricular ejection fractions were also noted in 5/6 nephrectomy mice treated with warfarin and active vitamin D3. Conclusion: Warfarin treatment contributes to the accelerated vascular calcification in animal models of advanced chronic kidney disease. Clinicians should therefore be aware of the profound risk of warfarin use on vascular calcification and cardiac dysfunction in patients with ESRD and atrial fibrillation. Keywords: Left ventricular dysfunction, Uremia, Vascular calcification, Warfarin

Rate of atherosclerosis progression in ApoE-/- mice long after discontinuation of cola beverage drinking.

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Matilde Otero-Losada

Full Text Available This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE-/- C57BL/6J mice (8 week-old were randomized in 3 groups (n = 20 each according to free accessto water (W, sucrose sweetened carbonated cola drink(C or aspartame-acesulfame K sweetened carbonated 'light' cola drink (Lfor the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8 weeks-old, at the end of treatment (16 weeks-old and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice. Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04 and mice age (F4,54 = 5.009, p<0.03 and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks. Natural evolution of atherosclerosis in ApoE-/- mice (W group evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8-16 weeks of age accelerated atherosclerosis progression in ApoE-/- mice favoring aortic plaque enlargement (inward remodeling over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE-/- mice.

Calcification of the heart: A rare manifestation of chronic renal failure

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Moraes, C.R. de

1986-01-01

A case is presented in which chronic renal failure led to intense visceral calcification, mainly to the lungs and heart. The discovery of cardiac calcifications on plain chest radiographs is exceedingly rare in renal patients. Puncate calcific deposits with an almost homogeneous distribution throughout the cardiac muscle were the main feature of this case. (orig.)

An unusual case of neonatal peritoneal calcifications associated with hydrometrocolpos

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Hu, M.X.; Methratta, S. [College of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark (United States). Dept. of Radiology

2001-10-01

Neonatal peritoneal calcifications usually suggest a diagnosis of meconium peritonitis, but in this case, a premature baby girl, peritoneal calcifications were caused by hydrometrocolpos secondary to imperforate hymen, a rare association. The patient presented with respiratory distress and ascites and demonstrated abdominal calcifications on plain film. Other radiographic work-up revealed hydrometrocolpos without evidence of gastrointestinal tract obstruction. The patient was diagnosed and treated for imperforate hymen; she was recovered fully. (orig.)

National Coral Reef Monitoring Program: Calcification Rates of Crustose Coralline Algae Derived from Calcification Accretion Units (CAUs) Deployed across the Hawaiian Archipelago in 2010

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National Oceanic and Atmospheric Administration, Department of Commerce — Calcification accretion units, or CAUs, are used to assess the current effects of changes in seawater carbonate chemistry on calcification and accretion rates of...

Nuclear medicine and atherosclerosis

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Sinzinger, H.; Virgolini, I.

1990-01-01

Although the pathomechanisms of atherosclerosis are well known, their radioisotopic monitoring is still in its early childhood. The current radioisotope techniques are of only limited value for contributing to the clinical diagnosis of atherosclerosis. The limited reaction time of cellular blood constituents (platelets, monocytes) with the vascular surface at the injury site makes it very difficult to catch the point of injury. Lipoproteins excellently allow receptor imaging, while vascular monitoring is only of scientific interest at present. Labelling and subsequent imaging of components of the coagulation cascade have not succeeded so far, nor have attempts using unspecific labels such as porphyrin, polyclonal IgG and Fc fragments, for example. Preliminary evidence indicates that radioisotopic techniques may be of great benefit in the future in elucidating functional aspects of the disease, while they do not contribute to examining the stage and extent of atherosclerosis. (orig.)

Calcification of the alar ligament of the cervical spine: imaging findings and clinical course

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Kobayashi, Yuka; Mochida, J.; Toh, E. [Dept. of Orthopaedic Surgery, Tokai Univ., Isehara, Kanagawa (Japan); Saito, Ikuo; Matui, Sizuka [Dept. of Orthopaedic Surgery, Odawara Hospital, Printing Bureau, Ministry of Finance, Sakawa, Odawara, Kanagawa (Japan)

2001-05-01

Ligamentous calcification of the cervical spine has been reported in the yellow ligament, anterior and posterior longitudinal ligaments and interspinous ligament. Calcification in the upper cervical spine is rare, although some cases with calcification of the transverse ligament of the atlas have been reported. Two patients with calcification of the alar ligament with an unusual clinical presentation and course are described. Examination by tomography and computed tomography (CT) showed calcification of the alar ligament and the transverse ligament of the atlas. CT documented decreased calcification as symptoms resolved. There may be a role for CT in the search for calcifications in the upper cervical spine in patients presenting with neck pain and pharyngodynia if radiographs are normal. (orig.)

Calcification of the alar ligament of the cervical spine: imaging findings and clinical course

International Nuclear Information System (INIS)

Kobayashi, Yuka; Mochida, J.; Toh, E.; Saito, Ikuo; Matui, Sizuka

2001-01-01

Ligamentous calcification of the cervical spine has been reported in the yellow ligament, anterior and posterior longitudinal ligaments and interspinous ligament. Calcification in the upper cervical spine is rare, although some cases with calcification of the transverse ligament of the atlas have been reported. Two patients with calcification of the alar ligament with an unusual clinical presentation and course are described. Examination by tomography and computed tomography (CT) showed calcification of the alar ligament and the transverse ligament of the atlas. CT documented decreased calcification as symptoms resolved. There may be a role for CT in the search for calcifications in the upper cervical spine in patients presenting with neck pain and pharyngodynia if radiographs are normal. (orig.)

Inflammation in renal atherosclerotic disease.

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Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

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AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients

Directory of Open Access Journals (Sweden)

Khaled AbouSeif

2016-01-01

Full Text Available Disorders associated with the hepatitis C virus (HCV have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC and corneal and conjunctival calcification (CCC in maintenance hemodialysis (MHD patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51 and seronegative patients (n = 49 regarding grading of AAC and CCC (P <0.001. Significant positive correlation was found between grading of CCC, AAC, age (P <0.001, duration on HD (P <0.001, HCV-antibody positivity (P <0.001, serum calcium level (P <0.001, serum phosphorus level (P <0.001, calcium × phosphorus product (P <0.001, and i-parathormone level (P < 0.001. In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Association of Aortic Calcification on Plain Chest Radiography with Obstructive Coronary Artery Disease

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Kang, Yeong Han; Chang, Jeong Ho [Dept. of Diagnostic Radiology, Daegu Catholic University Hospital, Daegu (Korea, Republic of); Park, Jong Sam [Dept. of Radiologic Tecnology, Daegu Health College, Daegu (Korea, Republic of)

2009-03-15

This study was conducted to determine an association between aortic calcification viewed on plain chest radiography and obstructive coronary artery disease. Retrospective review of all chest radiography obtained from consecutive patients undergoing coronary angiography. Chest PA images were reviewed by technical radiologist and radiologist. Considering the presence of aortic arch calcification, images were compared with the results of coronary angiography. In addition, the size of aortic arch calcification were divided into two groups - the smaller and the larger than 10 mm. Among the total 846 patients, the number of the patients with obstructive coronary artery disease is total 417 (88.3%) in males and 312 (83.4%) in females. Considering the presence of aortic arch calcification, the positive predictive value of relation between aortic arch calcification and obstructive coronary artery disease was 91.4% and the relative risk of the group with aortic arch calcification to the opposite group was 1.10. According to the size of aortic arch calcification and obstructive coronary artery disease, the positive predictive value was 91.9% and the relative risk between two groups was 1.04. This study shows that aortic calcification was closely associated with obstructive coronary artery disease. If the aortic calcification is notified on plain chest radiography, we strongly recommend to consult with doctor.

[Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

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