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Sample records for atherosclerosis

  1. Atherosclerosis

    Science.gov (United States)

    Atherosclerosis is a disease in which plaque builds up inside your arteries. Plaque is a sticky substance ... flow of oxygen-rich blood to your body. Atherosclerosis can lead to serious problems, including Coronary artery ...

  2. Atherosclerosis (image)

    Science.gov (United States)

    Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

  3. Molecular imaging in atherosclerosis

    NARCIS (Netherlands)

    Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.; Bozzao, Alessandro; Bonanno, Elena; Arca, Marcello; Dierckx, Rudi A. J. O.; Signore, Alberto

    2010-01-01

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (p

  4. 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...

  5. Histone deacetylases and atherosclerosis.

    Science.gov (United States)

    Zheng, Xia-xia; Zhou, Tian; Wang, Xin-An; Tong, Xiao-hong; Ding, Jia-wang

    2015-06-01

    Atherosclerosis is the most common pathological process that leads to cardiovascular diseases, a disease of large- and medium-sized arteries that is characterized by a formation of atherosclerotic plaques consisting of necrotic cores, calcified regions, accumulated modified lipids, smooth muscle cells (SMCs), endothelial cells, leukocytes, and foam cells. Recently, the question about how to suppress the occurrence of atherosclerosis and alleviate the progress of cardiovascular disease becomes the hot topic. Accumulating evidence suggests that histone deacetylases(HDACs) play crucial roles in arteriosclerosis. This review summarizes the effect of HDACs and HDAC inhibitors(HDACi) on the progress of atherosclerosis.

  6. How Is Atherosclerosis Treated?

    Science.gov (United States)

    ... symptoms Widening or bypassing plaque-clogged arteries Heart-Healthy Lifestyle Changes Your doctor may recommend heart-healthy lifestyle changes if you have atherosclerosis. Heart-healthy lifestyle ...

  7. Macrophage Autophagy in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Maria Chiara Maiuri

    2013-01-01

    Full Text Available Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility.

  8. Immune Vasculitis Induced Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The relationship between immune vasculitis and atherosclerosis was studied. The experimental model of weanling rabbits for immune vasculitis was reproduced by intravenous injection of 10 % bovine serum albumin. There were 6 groups: group A, 25 weanling rabbits with immune vasculitis subject to coronary arteriography; group B, 10 normal mature rabbits subject to coronary arteriography; group C, 10 weanling rabbits subject to coronary arteriography; group D, 8 weanling rabbits with vasculitis and cholesterol diet; group E, 8 weanling rabbits receiving single cholesterol diet; group F: 8 weanling rabbits receiving basic diet. Four weeks later, coronary arteriography was performed in groups A, B and C. The rabbits in groups D, E and F were sacrificed for the study of pathological changes in the coronary artery after 12 weeks. The results showed that the dilatation of coronary artery occurred in 6 rabbits of group A, but in groups B and C, no dilatation of coronary artery appeared. In comparison with group E, more severe atherosclerosis occurred in group D, showing the thickened plaque, fibrous sclerosis and atherosclerotic lesion. Percentage of plaques covering aortic intima, incidence of atherosclerosis of small coronary arteries and degree of stenosis of coronary arteries were significantly higher in group D than in group E (P<0.01). No atherosclerosis changes were found in group F. It was concluded that in the acute phase, the serum immune vasculitis can induce the dilatation of coronary artery of some weanling rabbits, and aggravate the formation of atherosclerosis in rabbits fed with cholesterol diet. Immune vasculitis is a new risk factor of atherosclerosis and ischemic heart disease.

  9. [Atherosclerosis and infection?].

    Science.gov (United States)

    Zeman, K

    2006-09-01

    Atherosclerosis is guided by chronicle inflammation process. In the last decades of the 20th century, studies considering infection another possible risk factor of atherosclerosis development were written. Helicobacter pylori, Porphyromas gingivalis, some viruses but most frequently Chlamydia pneumonie are infection agens mentioned in these studies. Some of them emphasize also combined infections caused by more pathogenic factors having influence on vascular inflammation. Serological, epidemiological, histological and imunological studies show the pathogenic influence of acute or chronic infections. Many studies selected makrolid antibiotics as treatment in patients with ischaemic heart disease. However, existing experience with antibiotics did not bring clear results. These studies have mentioned the fact antibiotics have not been indicated as treatment in patients with acute or chronic vascular system infliction by atherosclerosis. Since the experimental and clinical research of influence of inflammations on the development of atherosclerosis moved forward a lot, no exact evidence of this complicated pathogenic mechanism was given. It will obviously take some time to confirm whether the relation between infections and artherosclerosis is causal, i.e. initiating the pathogenic process, accelerating it or keeping it alive. PMID:17091609

  10. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    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.

  11. Genetic Susceptibility to Atherosclerosis

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    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  12. Alcohol and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Gao Yinglan; Song Jingyu; Jin Junshuo; Zhong Xiuhong; Ren Xiangshan; Liu Shuangping

    2005-01-01

    Objectives To study the relationship between alcohol and atherosclerosis (AS).Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imbalance of oxidationantioxidation system, oxygen free radical (OFR) and endothelium cell (EC) apoptosis, apoptosis and AS.Results Excessive alcohol could lead to imbalance of oxidation-antioxidation system, and increase OFR, in the meanwhile, OFR could lead to EC apoptosis,which could lead to AS.

  13. Blood pressure and atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008412 Association between single nucleotide polymorphisms of matrix metalloproteinase-3 gene and the severity of coronary atherosclerosis in patients with coronary artery disease. WU Naqiong(吴娜琼),et al. Cardiovasc Instit, Fuwai Hosp, Beijing 100037. Chin J Cardiol 2008;36(6):501-505. Objective To investigate the association between the severity of coronary arteries in patients with coronary artery disease and the single nucleotide polymorphisms of MMP-3 gene.

  14. Animal Models of Atherosclerosis

    OpenAIRE

    Godfrey S Getz; Reardon, Catherine A

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to...

  15. Role of Micronutrients on Subclinical Atherosclerosis Micronutrients in Subclinical Atherosclerosis.

    Science.gov (United States)

    Kocyigit, Duygu; Gurses, Kadri Murat; Yalcin, Muhammed Ulvi; Tokgozoglu, Lale

    2016-01-01

    Atherosclerotic cardiovascular disease (CVD) leading to coronary heart disease is the leading cause of morbidity and mortality in the world. Nutrition is one of the key factors in the etiology of atherosclerosis. Micronutrient supplements are widely used to prevent many chronic diseases including atherosclerosis. However, scientific evidence regarding this issue is still insufficient and current data on the association of dietary micronutrients and CVD risk is contradictory. Most of the randomized studies have failed to demonstrate beneficial effects of micronutrient supplementation on markers of subclinical atherosclerosis. In this review, role of each micronutrient on subclinical atherosclerosis will be evaluated thoroughly.

  16. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Murilo Foppa

    2001-02-01

    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  17. [PREDICTORS OF ATHEROSCLEROSIS: NEW DEVELOPMENTS].

    Science.gov (United States)

    Gozhenko, A I; Kotyuzhinskaya, S G; Kovalevskaya, L A

    2014-12-01

    The article describes known atherosclerosis predictors of endothelial origin, which are diagnostic criteria for identifying's early stages of atherosclerosis, and can prevent the development of this disease and are used to monitor the effectiveness of the therapy The authors analyzed the possibility of using heparin as an early marker of atherosclerosis, based on the fact that the inhibition of lipoprotein lipase activity due hyperheparinemia resulting from depletion of mast cells due to endothelial dysfunction, leads to the disorders of lipid transporting system in the form of the resistant hyperlipidemia with the phenomena of dyslipidemia. PMID:26638463

  18. Proteomic Biomarkers of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Natacha Diaz-Prieto

    2008-01-01

    Full Text Available Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The “omics” tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells as well as by circulating cells (monocytes, platelets or novel biomarkers present in plasma.

  19. Proteomic Biomarkers of Atherosclerosis.

    Science.gov (United States)

    Vivanco, F; Padial, L R; Darde, V M; de la Cuesta, F; Alvarez-Llamas, G; Diaz-Prieto, Natacha; Barderas, M G

    2008-01-01

    SUMMARY: Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The "omics" tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls) by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells) as well as by circulating cells (monocytes, platelets) or novel biomarkers present in plasma. PMID:19578499

  20. Intestinal Microbiota Metabolism and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Tian-Xing Liu; Hai-Tao Niu; Shu-Yang Zhang

    2015-01-01

    Objective:This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target.Data Sources:This study was based on data obtained from PubMed and EMBASE up to June 30,2015.Articles were selected using the following search temps:"Intestinal microbiota","trimethylamine N-oxide (TMAO)","trimethylamine (TMA)","cardiovascular",and "atherosclerosis".Study Selection:Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis.Studies on TMA-containing nutrients were also included.Results:A new CVD risk factor,TMAO,was recently identified.It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota,resulting in TMA release.TMA is subsequently converted to TMAO in the liver.Several preliminary studies have linked TMAO to CVD,particularly atherosclerosis;however,the details of this relationship remain unclear.Conclusions:Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management.

  1. Vitamin K Intake and Atherosclerosis

    Science.gov (United States)

    It has been hypothesized that insufficient intake of vitamin K may increase soft tissue calcification due to impaired gamma-carboxylation of the vitamin K-dependent protein, matrix gamma-carboxyglutamic acid (MGP). The evidence to support this putative role of vitamin K intake in atherosclerosis is ...

  2. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    DEFF Research Database (Denmark)

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S;

    2016-01-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B...... that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production...... of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis....

  3. [Is regression of atherosclerosis possible?].

    Science.gov (United States)

    Thomas, D; Richard, J L; Emmerich, J; Bruckert, E; Delahaye, F

    1992-10-01

    Experimental studies have shown the regression of atherosclerosis in animals given a cholesterol-rich diet and then given a normal diet or hypolipidemic therapy. Despite favourable results of clinical trials of primary prevention modifying the lipid profile, the concept of atherosclerosis regression in man remains very controversial. The methodological approach is difficult: this is based on angiographic data and requires strict standardisation of angiographic views and reliable quantitative techniques of analysis which are available with image processing. Several methodologically acceptable clinical coronary studies have shown not only stabilisation but also regression of atherosclerotic lesions with reductions of about 25% in total cholesterol levels and of about 40% in LDL cholesterol levels. These reductions were obtained either by drugs as in CLAS (Cholesterol Lowering Atherosclerosis Study), FATS (Familial Atherosclerosis Treatment Study) and SCOR (Specialized Center of Research Intervention Trial), by profound modifications in dietary habits as in the Lifestyle Heart Trial, or by surgery (ileo-caecal bypass) as in POSCH (Program On the Surgical Control of the Hyperlipidemias). On the other hand, trials with non-lipid lowering drugs such as the calcium antagonists (INTACT, MHIS) have not shown significant regression of existing atherosclerotic lesions but only a decrease on the number of new lesions. The clinical benefits of these regression studies are difficult to demonstrate given the limited period of observation, relatively small population numbers and the fact that in some cases the subjects were asymptomatic. The decrease in the number of cardiovascular events therefore seems relatively modest and concerns essentially subjects who were symptomatic initially. The clinical repercussion of studies of prevention involving a single lipid factor is probably partially due to the reduction in progression and anatomical regression of the atherosclerotic plaque

  4. DONOR-TRANSMITTED CORONARY ATHEROSCLEROSIS

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    B. L. Mironkov

    2014-01-01

    Full Text Available Aim. To estimate opportunities, prospects and safety of using heart transplants from aged donors who are at high risk of coronary atherosclerosis.Materials and methods. Over the period from March 1987 to May 2014450 heart transplantations (HTx were performed in V.I.Shumakov Federal Research Center of Transplantology and Artifi cial Organs. During the fi rst month after HTx coronarography was made to 152 (37,8% recipients inorder to exclude/confi rm donor-transmitted coronary atherosclerosis (DTCA and to identify tactics of treatment. Coronary atherosclerosis was detected among 16 patients (3,6% of total number of HTx, 15 (93,8% men and 1 (6,2% women. Mean age of recipients with DTCA at the moment of HTx was 48,3 ± 13,1 years.Results. Hemodynamically relevant coronary atherosclerosis was not detected and percutaneous coronary intervention (PCI was not made in the group of patients with the mean age of 42,24 ± 8,91 years. Using heart transplants from aged donors is connected with increasing risk of DTCA among the recipients. DTCA-dependent PCI is not connected with coronary mortality. Actuarial survival rate of patients who underwent PCI is comparable with the same one in the total population of HTx recipients and is equal to 87,5% at 5 years and less.Conclusion. Hearts from aged donors (older than 50 years may be used for HTx with suffi cient level of safety. Due to high level of DTCA using of hearts from such donors is preferable for completing urgent HTx to recipients 1А–В UNOS.

  5. Atherosclerosis in Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    Ewa Jednacz

    2012-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE or rheumatoid arthritis (RA. There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA. Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance.

  6. Cholesterol-Lowering Atherosclerosis Study (CLAS)

    Science.gov (United States)

    2013-12-12

    Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis

  7. 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.

  8. Atherosclerosis in Egyptian patients with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Dahlia A Hussein

    2014-01-01

    Conclusion Patients with AS are more susceptible to atherosclerosis, which is related to disease activity, and receiving biologics may place them at a higher risk. vWF, as a useful marker of atherosclerosis in AS patients, was correlated positively with disease activity scores and IMT.

  9. Rapid Progression of Coronary Atherosclerosis: A Review

    Directory of Open Access Journals (Sweden)

    Priyank Shah

    2015-01-01

    Full Text Available Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis.

  10. In-Vivo Assessment of Coronary Atherosclerosis

    NARCIS (Netherlands)

    G.A. Rodriguez-Granillo

    2006-01-01

    textabstractIntravascular ultrasound (IVUS) has emerged as a highly accurate tool for the serial assessment of the natural history of coronary atherosclerosis and to evaluate the effect of different conventional and emerging drug therapies on the progression of atherosclerosis. The contemporary a

  11. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    M.C.S. Boshuizen

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  12. Oral microbiota in patients with atherosclerosis

    DEFF Research Database (Denmark)

    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...... 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......: 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...

  13. Atherosclerosis

    Science.gov (United States)

    ... to help you stop smoking. Eat a heart-healthy diet. A heart-healthy diet includes a variety of fresh fruits and vegetables, ... High Cholesterol” for more on eating a heart-healthy diet. Talk to your doctor about adding supplements to ...

  14. Naringenin and atherosclerosis: a review of literature.

    Science.gov (United States)

    Orhan, Ilkay E; Nabavi, Seyed F; Daglia, Maria; Tenore, Gian C; Mansouri, Kowsar; Nabavi, Seyed M

    2015-01-01

    Atherosclerosis is a multifactorial disease mainly caused by deposition of low-density lipoprotein (LD) cholesterol in macrophages of arterial walls. Atherosclerosis leads to heart attacks as well as stroke. Epidemiological studies showed that there is an inverse correlation between fruit and vegetable consumption and the risk of atherosclerosis. The promising effect of high vegetable and fruit containing diet on atherosclerosis is approved by several experimental studies on isolated phytochemicals such as flavonoids. Flavonoids are known to up-regulate endogenous antioxidant system, suppress oxidative and nitrosative stress, decrease macrophage oxidative stress through cellular oxygenase inhibition as well as interaction with several signal transduction pathways and from these ways, have therapeutic effects against atherosclerosis. Naringenin is a well known flavonoid belonging to the chemical class of flavanones. It is especially abundant in citrus fruits, especially grapefruits. A plethora of evidences ascribes to naringenin antiatherosclerotic effects. Naringenin abilities to decrease LDL and triglycerides as well as inhibit glucose uptake; increase high-density lipoprotein (HDL); co-oxidation of NADH; suppress protein oxidation; protect against intercellular adhesion molecule-1(ICAM-1); suppress macrophage inflammation; inhibit leukotriene B4, monocyte adhesion and foam cell formation; induce of HO-1 and G 0/G 1 cell cycle arrest in vascular smooth muscle cells (VSMC) and down regulate atherosclerosis related genes are believed to have crucial role in the promising role against atherosclerosis. In the present review, we have summarized the available literature data on the anti-atherosclerotic effects of naringenin and its possible mechanisms of action.

  15. Macrophage plasticity in experimental atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Jamila Khallou-Laschet

    Full Text Available As in human disease, macrophages (MØ are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with progression of atherosclerosis in the apolipoprotein E (ApoE knockout (KO mouse model.We found that bone marrow-derived MØ submitted to M1 and M2 polarization specifically expressed arginase (Arg II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I(+ (M2 MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II(+ (M1 MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ phenotype. In order to address whether the M2->M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ in the lesion. The combined data therefore suggest that the M2->M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the MØ infiltrate towards the M2 phenotype may exert an atheroprotective action.

  16. The Progression and Early detection of Subclinical Atherosclerosis (PESA) study

    DEFF Research Database (Denmark)

    Fernández-Ortiz, Antonio; Jiménez-Borreguero, L Jesús; Peñalvo, José L;

    2013-01-01

    The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined.......The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined....

  17. Aorta Atherosclerosis Lesion Analysis in Hyperlipidemic Mice

    Science.gov (United States)

    Mohanta, Sarajo; Yin, Changjun; Weber, Christian; Hu, Desheng; Habenicht, Andreas JR

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. Apolipoprotein E-deficient (ApoE-/-) mice are used as experimental models to study human atherosclerosis. ApoE-/- mice are constitutively hyperlipidemic and develop intima plaques that resemble human plaques. Various issues including experimental design for lesion analysis, dietary conditions, isolation of the aorta, staining methods, morphometry, group size, age, the location within the arterial tree, and statistical analyses are important parameters that need to be addressed to obtain robust data. Here, we provide detailed methods to quantify aorta atherosclerosis. PMID:27366759

  18. Mouse models for atherosclerosis and pharmaceutical modifiers

    NARCIS (Netherlands)

    Zadelaar, A.S.M.; Kleemann, R.; Verschuren, L.; Vries-van der Weij, J. de; Hoorn, J. van der; Princen, H.M.; Kooistra, T.

    2007-01-01

    Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically

  19. Secondary Retroperitoneal Fibrosis Associated with Generalized Atherosclerosis

    OpenAIRE

    Barbullushi Myftar; Pasko Nevi; Bezhani Edip; Duraku Ahmet; Rusi Reza; Hoti Klit; Bakalli Vaso; Idrizi Alma

    1999-01-01

    Retroperitoneal fibrosis is an uncommon disease that often presents in a subtle manner. Only a few cases of the combined association of generalized atherosclerosis and retroperitoneal fibrosis are reported in the recent literature, supporting the view that the condition is probably an autoimmune periaortitis. We describe a typical case of retroperitoneal fibrosis associated with generalized atherosclerosis with clinical presentation of progressive renal insufficiency, and claudication from ar...

  20. Secondary Retroperitoneal Fibrosis Associated with Generalized Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Barbullushi Myftar

    1999-01-01

    Full Text Available Retroperitoneal fibrosis is an uncommon disease that often presents in a subtle manner. Only a few cases of the combined association of generalized atherosclerosis and retroperitoneal fibrosis are reported in the recent literature, supporting the view that the condition is probably an autoimmune periaortitis. We describe a typical case of retroperitoneal fibrosis associated with generalized atherosclerosis with clinical presentation of progressive renal insufficiency, and claudication from arterial compromise.

  1. 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.

  2. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    International Nuclear Information System (INIS)

    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

  3. Noninvasive assessment of preclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Helen A Lane

    2006-03-01

    Full Text Available Helen A Lane, Jamie C Smith, J Stephen DaviesDepartment of Endocrinology, University of Wales College of Medicine, Heath Park, Cardiff, Wales, UKAbstract: Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk.Keywords: endothelial function, vascular risk, vascular stiffness

  4. Metabolic syndrome, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rodolfo Paoletti

    2006-06-01

    Full Text Available Rodolfo Paoletti1,2, Chiara Bolego1, Andrea Poli2, Andrea Cignarella1,31Department of Pharmacological Sciences, University of Milan, Italy; 2Nutrition Foundation of Italy (NFI, Milan; 3Department of Pharmacology and Anesthesiology, University of Padova, ItalyAbstract: The inflammatory component of atherogenesis has been increasingly recognized over the last decade. Inflammation participates in all stages of atherosclerosis, not only during initiation and during evolution of lesions, but also with precipitation of acute thrombotic complications. The metabolic syndrome is associated with increased risk for development of both cardiovascular disease and type-2 diabetes in humans. Central obesity and insulin resistance are thought to represent common underlying factors of the syndrome, which features a chronic low-grade inflammatory state. Diagnosis of the metabolic syndrome occurs using defined threshold values for waist circumference, blood pressure, fasting glucose and dyslipidemia. The metabolic syndrome appears to affect a significant proportion of the population. Therapeutic approaches that reduce the levels of proinflammatory biomarkers and address traditional risk factors are particularly important in preventing cardiovascular disease and, potentially, diabetes. The primary management of metabolic syndrome involves healthy lifestyle promotion through moderate calorie restriction, moderate increase in physical activity and change in dietary composition. Treatment of individual components aims to control atherogenic dyslipidemia using fibrates and statins, elevated blood pressure, and hyperglycemia. While no single treatment for the metabolic syndrome as a whole yet exists, emerging therapies offer potential as future therapeutic approaches.Keywords: metabolic syndrome, systemic inflammation, coronary artery disease

  5. Chemokines and their receptors in Atherosclerosis.

    Science.gov (United States)

    van der Vorst, Emiel P C; Döring, Yvonne; Weber, Christian

    2015-09-01

    Atherosclerosis, a chronic inflammatory disease of the medium- and large-sized arteries, is the main underlying cause of cardiovascular diseases (CVDs) most often leading to a myocardial infarction or stroke. However, atherosclerosis can also develop without this clinical manifestation. The pathophysiology of atherosclerosis is very complex and consists of many cells and molecules interacting with each other. Over the last years, chemokines (small 8-12 kDa cytokines with chemotactic properties) have been identified as key players in atherogenesis. However, this remains a very active and dynamic field of research. Here, we will give an overview of the current knowledge about the involvement of chemokines in all phases of atherosclerotic lesion development. Furthermore, we will focus on two chemokines that recently have been associated with atherogenesis, CXCL12, and macrophage migration inhibitory factor (MIF). Both chemokines play a crucial role in leukocyte recruitment and arrest, a critical step in atherosclerosis development. MIF has shown to be a more pro-inflammatory and thus pro-atherogenic chemokine, instead CXCL12 seems to have a more protective function. However, results about this protective role are still quite debatable. Future research will further elucidate the precise role of these chemokines in atherosclerosis and determine the potential of chemokine-based therapies. PMID:26175090

  6. Osteoprotegerin as a marker of atherosclerosis

    DEFF Research Database (Denmark)

    Hosbond, Susanne Elisabeth; Poulsen, Tina Svenstrup; Diederichsen, Axel Cosmus Pyndt;

    2012-01-01

    Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD) a syste......Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD...... with clearly defined cohorts qualified for this review. Results: In 11 studies OPG concentrations were elevated. Severity of atherosclerosis was significantly associated with higher OPG concentrations compared to healthy controls. No association between PAD and OPG concentrations was observed. Conclusion: OPG...

  7. ATHEROSCLEROSIS DISEASE: A MULTI-FACTORIAL PATHOLOGY

    Directory of Open Access Journals (Sweden)

    Marcieli da Luz Giroldo1; Arienne Serrano Alves1; Francielle Baptista1

    2007-06-01

    Full Text Available Atherosclerosis or arterial stiffening is a gradual disease that restricts the normal blood flow in different areas of body and maylead to secondary illnesses as myocardial infarction and cerebral stroke. Innumerable factors are related to the development ofatherosclerosis, among them are the dyslipidemia; genetic factors; arterial hypertension; diabetes mellitus; obesity; smoking;lack of exercise; pulmonary infection by Chlamydia and stress. Due to multi-factorial atherosclerosis characteristics,innumerable drugs, with differentiated mechanisms of action, are being elaborated to be used in prevention and control of thisdisease. However, beyond the pharmacological therapy, a balanced diet, physical activity and elimination of risk habits, assmoking, also are need for controlling atherosclerosis progression, as well as for the increase of expectative and quality of life

  8. Association between arterial stiffness and atherosclerosis: the Rotterdam Study

    NARCIS (Netherlands)

    N.M-L. van Popele (Nicole); D.E. Grobbee (Diederick); M.L. Bots (Michiel); R. Asmar (Roland); J. Topouchian; R.S. Reneman; A.P.G. Hoeks; D.A. van der Kuip (Deirdre); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractBACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted w

  9. Atherosclerosis: Process, Indicators, Risk Factors and New Hopes

    Directory of Open Access Journals (Sweden)

    Mahmoud Rafieian-Kopaei

    2014-01-01

    Conclusions: The pathogenesis factors involved in atherosclerosis have recently been cleared and the discovery of these factors has brought about new hopes for better prevention and treatment of atherosclerosis.

  10. Imaging Atherosclerosis in Diabetes: Current State.

    Science.gov (United States)

    Rahmani, Sina; Nakanishi, Rine; Budoff, Matthew J

    2016-11-01

    Cardiovascular events, including myocardial infarction and stroke, are the primary causes of mortality in both type 1 and type 2 diabetes. Affected patients frequently have asymptomatic coronary artery disease. Studies have shown heterogeneity in cardiovascular risk among patients with diabetes. Imaging can help categorize risk of future cardiovascular events by identifying those patients with atherosclerosis, rather than relying on risk prediction based on population-based studies. In this article, we will review the evidence regarding use of atherosclerosis imaging in patients with diabetes to predict risk of coronary heart disease and mortality. PMID:27658933

  11. [The treatment of atherosclerosis--drug therapy].

    Science.gov (United States)

    Nakamura, H; Takahashi, Y

    1993-08-01

    Drug treatment against atherosclerosis has been evaluated recently in many epidemiological studies. Lipid Research Clinics Group convincingly reported in a large scale design that anion exchange resin effectively reduced blood cholesterol level and concomitantly decreased the events of coronary heart disease. Subsequently, anion exchange resin with or without combined administration of niacin or statin was found to inhibit the progression of coronary atherosclerotic lesions in FATS, SCOR, CLAS and STARS. Fenofibrate also successfully reduced the coronary artery narrowings. Based on these intervention studies, several hypocholesterolemic agents are definitely effective in the treatment of coronary atherosclerosis.

  12. Atherosclerotic Plaque Vulnerability in Experimental Models of Atherosclerosis

    NARCIS (Netherlands)

    D. Segers (Dolf)

    2011-01-01

    textabstractAtherosclerosis is a chronic and often progressive disease of the wall of the arterial vasculature. The term atherosclerosis is derived from the Greek words “athero” meaning gruel or paste and “skleros” meaning stiff or hard. Atherosclerosis is considered a major clinical problem, which

  13. LDL oxidation and extent of coronary atherosclerosis

    NARCIS (Netherlands)

    Vijver, L.P.L. van de; Kardinaal, A.F.M.; Duyvenvoorde, W. van; Kruijssen, D.A.C.M.; Grobbee, D.E.; Poppel, G. van; Princen, H.M.G.

    1998-01-01

    Accumulated evidence indicates that oxidative modification of LDL plays an important role in the atherogenic process. Therefore, we investigated the relation between coronary atherosclerosis and susceptibility of LDL to oxidation in a case-control study in men between 45 and 80 years of age. Case su

  14. Imaging of coronary atherosclerosis: Intravascular ultrasound

    NARCIS (Netherlands)

    H.M. Garcia-Garcia (Hector); M.A. Costa (Marco); P.W.J.C. Serruys (Patrick)

    2010-01-01

    textabstractAtherosclerosis is the main cause of coronary heart disease, which is today the leading cause of death worldwide and will continue to be the first in the world in 2030. In the formation of atherosclerotic coronary lesions, a critical primary step is the accumulation and oxidation of low-

  15. Crosstalk between apoptosis and inflammation in atherosclerosis

    NARCIS (Netherlands)

    Westra, Marijke Marianne

    2010-01-01

    In this thesis the role of several apoptosis regulating proteins in the development of atherosclerosis and atherosclerotic plaque stability is investigated. Apoptosis of different cell types in atherosclerotic plaques, such as macrophages and smooth muscle cells may inhibit or promote plaque develop

  16. Photoacoustic tomography: applications for atherosclerosis imaging

    Science.gov (United States)

    Sangha, Gurneet S.; Goergen, Craig J.

    2016-08-01

    Atherosclerosis is a debilitating condition that increases a patient’s risk for intermittent claudication, limb amputation, myocardial infarction, and stroke, thereby causing approximately 50% of deaths in the western world. Current diagnostic imaging techniques, such as ultrasound, digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and optical imaging remain suboptimal for detecting development of early stage plaques. This is largely due to the lack of compositional information, penetration depth, and/or clinical efficiency of these traditional imaging techniques. Photoacoustic imaging has emerged as a promising modality that could address some of these limitations to improve the diagnosis and characterization of atherosclerosis-related diseases. Photoacoustic imaging uses near-infrared light to induce acoustic waves, which can be used to recreate compositional images of tissue. Recent developments in photoacoustic techniques show its potential in noninvasively characterizing atherosclerotic plaques deeper than traditional optical imaging approaches. In this review, we discuss the significance and development of atherosclerosis, current and novel clinical diagnostic methods, and recent works that highlight the potential of photoacoustic imaging for both experimental and clinical studies of atherosclerosis.

  17. Mechanisms of MicroRNAs in Atherosclerosis.

    Science.gov (United States)

    Schober, Andreas; Weber, Christian

    2016-05-23

    The maladaptation of endothelial cells to disturbed flow at arterial bifurcations increases permeability for lipoproteins. Additional injury by chemically modified lipoproteins disrupts the continuous repair of maladapted endothelial cells and triggers intimal macrophage accumulation. Macrophages remove modified lipoproteins from the extracellular space until the cholesterol overload leads to macrophage death and insufficient efferocytosis. This macrophage failure promotes the progression to advanced lesions by formation of a lipid-rich necrotic core, which may rupture and cause myocardial infarction and stroke. In this article, we summarize the fundamental roles of microRNAs (miRNAs) in the regulation of endothelial maladaptation and macrophage failure during atherosclerosis. We describe how miRNAs coordinate the mutual interaction between chronic endothelial repair and endothelial senescence and mechanistically link the regulation of macrophage cholesterol homeostasis with defective efferocytosis. Lastly, we discuss how miRNAs may challenge and extend current theories about atherosclerosis. PMID:27193456

  18. Atherosclerosis in elderly patients with renal insufficiency

    Institute of Scientific and Technical Information of China (English)

    Sandeep S. Soman

    2005-01-01

    @@ Introduction As people age,cardiovascular structure and function change and this is superimposed on by specific pathophysiologic disease mechanism.In addition to lipid levels,diabetes,sedentary lifestyle,and genetic factors that are known risks for coronary disease,hypertension,and stroke - the quintessential cardiovascular (CV) diseases related to atherosclerosis within our society - advancing age unequivocally confers the major risk.(Fig.1) Mortality due to cardiovascular disease is more than any other disease and creates enormous costs for the health care system.The main underlying problem in cardiovascular disease is atherosclerosis,a process that obstructs major arteries with lipid deposits and cell accumulation.1 Decreased kidney function (estimated GFR<70 mL/min/1.73 m2) is an independent risk factor for cardiovascular disease and all-cause mortality in the general population.2

  19. Prevention and Regression of Atherosclerosis: Emerging Treatments

    Directory of Open Access Journals (Sweden)

    Aliosvi Rodríguez Rodríguez

    2014-06-01

    Full Text Available Occlusive vascular diseases such as acute coronary syndrome, cerebral stroke, and peripheral arterial disease, represent a serious health problem worldwide. In recent decades, there has been significant progress in the diagnosis and treatment of atherosclerosis. Intravascular ultrasound imaging provides detailed information on the anatomy of the plaque and it has been used in several studies to evaluate the results. Atherosclerosis destabilizes the normal protective mechanism provided by the endothelium and this mechanism has been involved in the pathophysiology of acute coronary disease and brain stroke. Main efforts focus on prevention, especially at early ages. This paper is a review of 68 updated bibliographic citations in order to show the current options available for the prevention and reversal of the atherosclerotic process.

  20. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    Science.gov (United States)

    Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

    2016-02-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID:26809711

  1. Lysophosphatidic acid effects on atherosclerosis and thrombosis

    OpenAIRE

    Cui, Mei-Zhen

    2011-01-01

    Lysophosphatidic acid (LPA) has been found to accumulate in high concentrations in atherosclerotic lesions. LPA is a bioactive phospholipid produced by activated platelets and formed during the oxidation of LDL. Accumulating evidence suggests that this lipid mediator may serve as an important risk factor for development of atherosclerosis and thrombosis. The role of LPA in atherogenesis is supported by the evidence that LPA: stimulates endothelial cells to produce adhesion molecules and chemo...

  2. Mitogen-activated protein kinases in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Dorota Bryk

    2014-01-01

    Full Text Available Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase, JNK (c-Jun N-terminal kinase and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis.

  3. Doinseunggitang Ameliorates Endothelial Dysfunction in Diabetic Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jung Joo Yoon

    2013-01-01

    Full Text Available Atherosclerosis, a chronic and progressive disease characterized by vascular inflammation, is a leading cause of death in diabetes patients. Doinseunggitang (DYSGT, traditional prescription, has been used for promoting blood circulation to remove blood stasis. The aim of this study was to investigate the beneficial effects of DYSGT on endothelial dysfunction in diabetic atherosclerosis animal model. Apolipoprotein E knockout (ApoE KO mice fed on a Western diet were treated with DYSGT (200 mg/kg/day. DYSGT significantly lowered blood glucose level and glucose tolerance as well as systolic blood pressure. Metabolic parameter showed that DYSGT markedly decreased triglyceride and LDL-cholesterol levels. In the thoracic aorta, the impairment of vasorelaxation response to acetylcholine and atherosclerotic lesion was attenuated by DYSGT. Furthermore, DYSGT restored the reduction of endothelial nitric oxide synthase (eNOS expression, leading to the inhibition of intracellular adhesion molecule-1 (ICAM-1 and endothelin-1 (ET-1 expression. In conclusion, DYSGT improved the development of diabetic atherosclerosis via attenuation of the endothelial dysfunction, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation. Therefore, these results suggest that Korean traditional prescription Doinseunggitang may be useful in the treatment and prevention of diabetic vascular complications.

  4. LDL biochemical modifications: a link between atherosclerosis and aging

    Directory of Open Access Journals (Sweden)

    Matilde Alique

    2015-12-01

    Full Text Available Atherosclerosis is an aging disease in which increasing age is a risk factor. Modified low-density lipoprotein (LDL is a well-known risk marker for cardiovascular disease. High-plasma LDL concentrations and modifications, such as oxidation, glycosylation, carbamylation and glycoxidation, have been shown to be proatherogenic experimentally in vitro and in vivo. Atherosclerosis results from alterations to LDL in the arterial wall by reactive oxygen species (ROS. Evidence suggests that common risk factors for atherosclerosis raise the likelihood that free ROS are produced from endothelial cells and other cells. Furthermore, oxidative stress is an important factor in the induction of endothelial senescence. Thus, endothelial damage and cellular senescence are well-established markers for atherosclerosis. This review examines LDL modifications and discusses the mechanisms of the pathology of atherosclerosis due to aging, including endothelial damage and oxidative stress, and the link between aging and atherosclerosis.

  5. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    OpenAIRE

    Xin-Fang Leong; Chun-Yi Ng; Kamsiah Jaarin

    2015-01-01

    Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Co...

  6. Atherosclerosis: a chronic inflammatory disease mediated by mast cells

    OpenAIRE

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endotheli...

  7. Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Zech Loren A

    2008-03-01

    Full Text Available Abstract Background A relationship between corneal arcus and atherosclerosis has long been suspected but is controversial. The homozygous familial hypercholesterolemia patients in this study present a unique opportunity to assess this issue. They have both advanced atherosclerosis and corneal arcus. Methods This is a cross-sectional study of 17 patients homozygous for familial hypercholesterolemia presenting to the Clinical Center of the National Institutes of Health. Plasma lipoproteins, circumferential extent of arcus, thoracic aorta and coronary calcific atherosclerosis score, and Achilles tendon width were measured at the National Institutes of Health. Results Patients with corneal arcus had higher scores for calcific atherosclerosis (mean 2865 compared to 412, cholesterol-year score (mean 11830 mg-yr/dl compared to 5707 mg-yr/dl, and Achilles tendon width (mean 2.54 cm compared to 1.41 cm than those without. Corneal arcus and Achilles tendon width were strongly correlated and predictive of each other. Although corneal arcus was correlated with calcific atherosclerosis (r = 0.67; p = 0.004, it was not as highly correlated as was the Achilles tendon width (r = 0.855; p Conclusion Corneal arcus reflects widespread tissue lipid deposition and is correlated with both calcific atherosclerosis and xanthomatosis in these patients. Patients with more severe arcus tend to have more severe calcific atherosclerosis. Corneal arcus is not as good an indicator of calcific atherosclerosis as Achilles tendon thickness, but its presence suggests increased atherosclerosis in these hypercholesterolemic patients.

  8. Study on Atherosclerosis Treated with Theory of Detoxification

    Institute of Scientific and Technical Information of China (English)

    Xu Yingchun; Wang Hualiang; Ding Jing

    2006-01-01

    Starting with the contents, classification and pathogenic characteristics of the toxic pathogen and combining the modem medical research on the correlation of atherosclerosis with inflammation and immune reaction,authors have studied and expounded the interrelationship between the toxic pathogen and atherosclerosis.The toxic pathogen affecting the whole pathological process of atherosclerosis is a key factor for the disease to remain lingering and a cause of various cardiocerebrovascular diseases. Detoxification can be used to treat atherosclerosis so as to enhance the toxin-removing ability of the body and resist the damage to the body from the toxic pathogen.

  9. (-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Hansen, B F; Mortensen, A; Hansen, J F;

    1995-01-01

    Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups...... differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower...... (p atherosclerosis in the abdominal aorta in WHHL rabbits....

  10. The paradoxical role of IL-17 in atherosclerosis.

    Science.gov (United States)

    Gong, Fangchen; Liu, Zhengxia; Liu, Jingning; Zhou, Ping; Liu, Ying; Lu, Xiang

    2015-09-01

    Atherosclerosis is a chronic inflammatory disease mediated by innate and adaptive immune responses. In recent years, CD4(+) T cells (Th1, Th2, Treg, and Th17) have been increasingly studied for their role in atherosclerosis pathophysiology, atheroma stability, plaque rupture, and life-threatening acute coronary syndrome. IL-17, a marker cytokine of Th17 cells, has been reported to be involved in the pathogenesis of rheumatoid arthritis, inflammatory bowel disease, and asthma. However, its role in atherosclerosis has been poorly characterized. This article provides a comprehensive overview of the role of IL-17 in the development of atherosclerosis and human coronary artery diseases. PMID:26077826

  11. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography.

    Science.gov (United States)

    Scherer, Daniel J; Psaltis, Peter J

    2016-08-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of (18)Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of (18)Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF). PMID:27500093

  12. Targeting and Therapeutic Peptides in Nanomedicine for Atherosclerosis

    OpenAIRE

    Chung, Eun Ji

    2016-01-01

    Peptides in atherosclerosis nanomedicine provide structural, targeting, and therapeutic functionality, and can assist in overcoming delivery barriers of traditional pharmaceuticals. Moreover, their inherent biocompatibility and biodegradability make them especially attractive as materials intended for use in vivo. In this review, an overview of nanoparticle-associated targeting and therapeutic peptides for atherosclerosis are provided, including peptides designed for cellular targets such as ...

  13. Novel experimental therapies for atherosclerosis : a genomics based approach

    NARCIS (Netherlands)

    Wanrooij, Eva Josephine Anna van

    2007-01-01

    Atherosclerosis is a progressive disease of the large arteries characterized by lipid deposition, inflammation, cell death and fibrosis and it is the major cause of death in the Western world. In this thesis new and experimental therapies against atherosclerosis are designed and tested. New targets

  14. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    Science.gov (United States)

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  15. Molecular imaging of atherosclerosis in translational medicine

    Energy Technology Data Exchange (ETDEWEB)

    Perrone-Filardi, Pasquale; Costanzo, Pierluigi; Marciano, Caterina; Vassallo, Enrico; Marsico, Fabio; Ruggiero, Donatella; Petretta, Maria Piera; Chiariello, Massimo [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy); Dellegrottaglie, Santo [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy); Mount Sinai Medical Center, Z. and M.A. Wiener Cardiovascular Institute and M.-J. and H.R. Kravis Center for Cardiovascular Health, New York, NY (United States); Rudd, James H.F. [University of Cambridge, School of Clinical Medicine, Cambridge (United Kingdom); Cuocolo, Alberto [University Federico II, Department of Biomorphological and Functional Sciences, Naples (Italy); SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples (Italy)

    2011-05-15

    Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events. (orig.)

  16. Periodontitis as a Risk Factor of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jirina Bartova

    2014-01-01

    Full Text Available Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis.

  17. [Key laboratory diagnostic biomarkers of coronary atherosclerosis].

    Science.gov (United States)

    Ragino, Iu I; Cherniavskiĭ, A M; Eremenko, N V; Shakhtshneĭder, E V; Polonskaia, Ia V; Tsymbal, S Iu; Ivanova, M V; Voevoda, M I

    2011-01-01

    Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation. PMID:21627612

  18. The relationship between atherosclerosis and pulmonary emphysema

    Directory of Open Access Journals (Sweden)

    Vučević Danijela

    2014-01-01

    Full Text Available Introduction. The etiopathogenesis of atherosclerosis and subsequent pulmonary emphysema has not been fully elucidated. Experimental Studies Foam cells are of great importance in the development of these diseases. It is known that local cytokine secretion and modification of native lipoprotein particles, which are internalized by the vascular and alveolar macrophages via the scavenger receptors on the surfaces of these cells, lead to the formation of foam cells. Thus, the exacerbation of local inflammatory process in the vascular and lung tissue ensues due to a generation of reactive oxygen species, resulting in further lipoprotein modification and cytokine production. Accumulating evidence suggests that oxidants may facilitate the inflammatory response by impairing antiprotease function, directly attacking vascular and lung matrix proteins and by inactivating enzymes involved in elastin synthesis and vascular and lung repair. Clinical Studies Cigarette smoke is recognized as a rich source of oxidants. Nearly 90% of all patients with chronic obstructive pulmonary disease are smokers. The process of atherogenesis is also influenced by tobacco smoke. Conclusion The role of vascular and alveolar macrophages has become increasingly important in understanding the development of atherosclerosis and resulting pulmonary emphysema.[Projekat Ministarstva nauke Republike Srbije, br. 175015

  19. Activated TLR signaling in atherosclerosis among women with lower Framingham risk score: the multi-ethnic study of atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Chiang-Ching Huang

    Full Text Available BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease (CVD. Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis. RESULTS: A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (100 and carotid intima-media thickness (IMT >1.0 mm, whereas controls (N = 71 had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001; among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001. Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis. CONCLUSION: Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.

  20. 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....

  1. High density lipoproteins and atherosclerosis: emerging aspects

    Institute of Scientific and Technical Information of China (English)

    Federica Sala; Alberico Luigi Catapano; Giuseppe Danilo Norata

    2012-01-01

    High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes.Furthermore, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis.

  2. Chlamydia pneumoniae and Atherosclerosis: The End?

    Directory of Open Access Journals (Sweden)

    LE Nicolle

    2005-01-01

    Full Text Available In this issue of the Journal, Patrick et al (pages 298-300 report on the results of a pilot study testing the hypothesis that seropositivity to Chlamydia pneumoniae together with a specific bacteriophage protein is associated with first-episode myocardial infarction or unstable angina. The study evolved from an earlier report suggesting that C pneumoniae with phage seropositivity was strongly associated with the presence of abdominal aortic aneurysm. The phage association suggested a potential explanation for some of the variability in previous studies exploring C pneumoniae as a cause for atherosclerosis (ie, only selected strains of C pneumoniae were pathogenic. Patrick et al found no significant association or trend, and the authors concluded that the negative findings in their pilot study did not support further studies to address this potential association.

  3. Homocysteine and the pathogenesis of atherosclerosis.

    Science.gov (United States)

    McCully, Kilmer S

    2015-03-01

    The homocysteine theory of arteriosclerosis was discovered by study of arteriosclerotic plaques occurring in homocystinuria, a disease caused by deficiencies of cystathionine synthase, methionine synthase or methylenetetrahydrofolate reductase. According to the homocysteine theory, metabolic and nutritional abnormalities leading to elevation of plasma homocysteine cause atherosclerosis in the general population without these rare enzymatic abnormalities. Through studies of metabolism of homocysteine thiolactone, the anhydride of homocysteine, in cell cultures from homocystinuric children, the pathway for synthesis of sulfate was found to be dependent upon thioretinamide, the amide formed from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide form the complex thioretinaco with cobalamin, and oxidative phosphorylation is catalyzed by reduction of oxygen, which is bound to thioretinaco ozonide, by electrons from electron transport particles. Atherogenesis is attributed to formation of aggregates of homocysteinylated lipoproteins with microorganisms, which obstruct the vasa vasorum during formation of arterial vulnerable plaques. PMID:25653125

  4. Effect of age on aortic atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Michael A. Chen; Miwa Kawakubo; Patrick M. Colletti; Dongxiang Xu; Laurie LaBree Dustin; Robert Detrano; Stanley P Azen; Nathan D. Wong; Xue-Qiao Zhao

    2013-01-01

    Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). Methods A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated. Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI × 100. Results In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area and wall thickness were 222 ± 45 mm2 and 2.7 ± 0.4 mm, respectively. Maximum wall thickness was 3.4 ± 0.6 mm, and PWV was 32% ± 4%. Women appeared to have smaller wall area, but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associated with larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors, Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcification was associated with coronary calcification. Conclusions Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, and women had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.

  5. Ventilatory chaos is impaired in carotid atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Laurence Mangin

    Full Text Available Ventilatory chaos is strongly linked to the activity of central pattern generators, alone or influenced by respiratory or cardiovascular afferents. We hypothesized that carotid atherosclerosis should alter ventilatory chaos through baroreflex and autonomic nervous system dysfunctions. Chaotic dynamics of inspiratory flow was prospectively evaluated in 75 subjects undergoing carotid ultrasonography: 27 with severe carotid stenosis (>70%, 23 with moderate stenosis (<70%, and 25 controls. Chaos was characterized by the noise titration method, the correlation dimension and the largest Lyapunov exponent. Baroreflex sensitivity was estimated in the frequency domain. In the control group, 92% of the time series exhibit nonlinear deterministic chaos with positive noise limit, whereas only 68% had a positive noise limit value in the stenoses groups. Ventilatory chaos was impaired in the groups with carotid stenoses, with significant parallel decrease in the noise limit value, correlation dimension and largest Lyapunov exponent, as compared to controls. In multiple regression models, the percentage of carotid stenosis was the best in predicting the correlation dimension (p<0.001, adjusted R(2: 0.35 and largest Lyapunov exponent (p<0.001, adjusted R(2: 0.6. Baroreflex sensitivity also predicted the correlation dimension values (p = 0.05, and the LLE (p = 0.08. Plaque removal after carotid surgery reversed the loss of ventilatory complexity. To conclude, ventilatory chaos is impaired in carotid atherosclerosis. These findings depend on the severity of the stenosis, its localization, plaque surface and morphology features, and is independently associated with baroreflex sensitivity reduction. These findings should help to understand the determinants of ventilatory complexity and breathing control in pathological conditions.

  6. Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yavuz Beyazit

    2011-01-01

    Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

  7. Toll-Like Receptors, Their Ligands, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Conrad P. Hodgkinson

    2011-01-01

    Full Text Available Atherosclerosis is a disease characterized by inflammation in the arterial wall. Atherogenesis is dependent on the innate immune response involving activation of Toll-like receptors (TLRs and the expression of inflammatory proteins. TLRs, which recognize various pathogen-associated molecular patterns, are expressed in various cell types within the atherosclerotic plaque. Microbial agents are associated with an increased risk of atherosclerosis and this is, in part, due to activation of TLRs. Recently considerable evidence has been provided suggesting that endogenous proteins promote atherosclerosis by binding to TLRs. In this review, we describe the role of TLRs in atherosclerosis with particular emphasis on those atherogenic endogenous proteins that have been implicated as TLR ligands.

  8. Inflammatory and Autoimmune Reactions in Atherosclerosis and Vaccine Design Informatics

    Directory of Open Access Journals (Sweden)

    Michael Jan

    2010-01-01

    Full Text Available Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide. As its complex pathogenesis has been gradually unwoven, the regime of treatments and therapies has increased with still much ground to cover. Active research in the past decade has attempted to develop antiatherosclerosis vaccines with some positive results. Nevertheless, it remains to develop a vaccine against atherosclerosis with high affinity, specificity, efficiency, and minimal undesirable pathology. In this review, we explore vaccine development against atherosclerosis by interpolating a number of novel findings in the fields of vascular biology, immunology, and bioinformatics. With recent technological breakthroughs, vaccine development affords precision in specifying the nature of the desired immune response—useful when addressing a disease as complex as atherosclerosis with a manifold of inflammatory and autoimmune components. Moreover, our exploration of available bioinformatic tools for epitope-based vaccine design provides a method to avoid expenditure of excess time or resources.

  9. Iron and hepcidin as risk factors in atherosclerosis

    DEFF Research Database (Denmark)

    Galesloot, Tessel E; Janss, Luc L; Burgess, Stephen;

    2015-01-01

    BACKGROUND: Previous reports suggested a role for iron and hepcidin in atherosclerosis. Here, we evaluated the causality of these associations from a genetic perspective via (i) a Mendelian randomization (MR) approach, (ii) study of association of atherosclerosis-related single nucleotide...... polymorphisms (SNPs) with iron and hepcidin, and (iii) estimation of genomic correlations between hepcidin, iron and atherosclerosis. RESULTS: Analyses were performed in a general population sample. Iron parameters (serum iron, serum ferritin, total iron-binding capacity and transferrin saturation), serum...... hepcidin and genome-wide SNP data were available for N = 1,819; non-invasive measurements of atherosclerosis (NIMA), i.e., presence of plaque, intima media thickness and ankle-brachial index (ABI), for N = 549. For the MR, we used 12 iron-related SNPs that were previously identified in a genome...

  10. [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 atheros......[(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...... of atherosclerosis, and reports recommendations to optimize imaging protocols....

  11. Risk Analysis on Uric Acid Resulting in Carotid Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    肖敏; 李河; 郭兰; 石美铃; 麦劲壮

    2004-01-01

    Objectives To explore the risk of uric acid (UA) resulting in carotid atherosclerosis. Methods With a cross sectional study, 643 subjects (aged 41-83 yrs, male 552 and female 91)were surveyed in 1999 in Guangdong Province, China.The main research variables were uric acid (UA), occurrence and the size of carotid artery plaque. Results There was no statistical significance between the UA means of plaque occurrence and no-occurrence groups (t=0.60, df=242, P=0.5495). It seemed UA was not a possible risk factor of carotid atherosclerosis (OR=1.060, P=-0.8448>0.05, n=244) based on the logistic regression analysis. Conclusions Our results are not consistent with serum UA being an independent risk factor for atherosclerosis and coronary heart disease (CHD). It is necessary to do more research to learn the risk degree of UA during the progress of atherosclerosis/CHD.

  12. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis.

    Science.gov (United States)

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE -/- mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come.

  13. T Lymphocyte Autoreactivity in Inflammatory Mechanisms Regulating Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Elisabetta Profumo

    2012-01-01

    Full Text Available Atherosclerosis has been clearly demonstrated to be a chronic inflammatory disease of the arterial wall. Both cells of the innate and the acquired immune system, particularly monocytes and T lymphocytes, are implicated in the atherogenic process, producing different cytokines with pro- and anti-inflammatory effects. The majority of pathogenic T cells involved in atherosclerosis are of the Th1 profile, that has been correlated positively with coronary artery disease. Many studies conducted to evaluate the molecular factors responsible for the activation of T cells have demonstrated that the main antigenic targets in atherosclerosis are modified endogenous structures. These self-molecules activate autoimmune reactions mainly characterized by the production of Th1 cytokines, thus sustaining the inflammatory mechanisms involved in endothelial dysfunction and plaque development. In this paper we will summarize the different T-cell subsets involved in atherosclerosis and the best characterized autoantigens involved in cardiovascular inflammation.

  14. Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study

    Science.gov (United States)

    2016-02-05

    Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial Infarction; Heart Diseases; Diabetes Mellitus, Non-insulin Dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus

  15. [The role of infection in the pathogenesis of atherosclerosis].

    Science.gov (United States)

    Banach, Maciej; Markuszewski, Leszek; Zasłonka, Janusz; Grzegorczyk, Janina; Okoński, Piotr; Jegier, Bogdan

    2004-01-01

    Experimental models and human studies have supported a role of infection in the initiation of atherosclerosis. There are many known microorganisms who can play an important role in atherosclerosis, but especially two of them--Chlamydia pneumoniae and Cytomegalovirus are suspected to stimulate the process of atheromatosis. Until antibiotics or vaccines are useful in artery diseases prevention, therapies with proven vascular anti-inflammatory effects (diet, exercise, smoking cessation, aspirin, statins) should be optimized. PMID:15810509

  16. Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis

    OpenAIRE

    Aliev, G; Burnstock, G.

    1998-01-01

    Many factors play important roles in the development of atherosclerotic lesions. The leading risk factor for atherosclerosis is familial hypercholesterolaemia (FH). FH is a genetic disease characterized by a deficiency of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells, a high level of serum LDL, and early development of atherosclerosis and skin xanthoma. Watanabe and colleagues have developed a line of rabbits with unprovoke...

  17. Atherosclerosis and Thrombosis: Insights from Large Animal Models

    OpenAIRE

    Gemma Vilahur; Teresa Padro; Lina Badimon

    2011-01-01

    Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination of in vitro, ex vivo, and in vivo experimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protei...

  18. C-Peptide: A New Mediator of Atherosclerosis in Diabetes

    Directory of Open Access Journals (Sweden)

    Dusica Vasic

    2012-01-01

    Full Text Available Diabetes type 2 and insulin resistance are the risk factors for cardiovascular disease. It is already known that atherosclerosis is an inflammatory disease, and a lot of different factors are involved in its onset. C-peptide is a cleavage product of proinsulin, an active substance with a number of effects within different complications of diabetes. In this paper we discuss the role of C-peptide and its effects in the development of atherosclerosis in type 2 diabetic patients.

  19. 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...... in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis....

  20. (18)F-FDG PET imaging of murine atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina;

    2012-01-01

    To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice.......To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice....

  1. Baroreflex dysfunction promotes the induction of atherosclerosis in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-junCAI; Chao-yuMIAO; He-huiXIE; Ding-fengSU

    2004-01-01

    AIM: To testify the hypothesis that arterial baroreflex dysfunction promotes the induction of atherosclerosis. METHODSAND RESULTS: Experiment 1 : The baroreflex sensitivity (BRS) was measured in 30 SD rats in conscious state with a computerized blood pressure monitoring system. Four weeks later, the rats were fed with a high-cholesterol diet for 8-week duration to induce atherosclerosis. The hearts and aortae were removed for pathological examination and the scores of coronary and aortic

  2. Matrix metalloproteinase inhibition in atherosclerosis and stroke.

    Science.gov (United States)

    Roycik, M D; Myers, J S; Newcomer, R G; Sang, Q-X A

    2013-09-01

    Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc-dependent proteases that degrade extracellular matrix (ECM), cell surface, and intracellular proteins. Vascular remodeling, whether as a function of normal physiology or as a consequence of a myriad of pathological processes, requires degradation of the ECM. Thus, the expression and activity of many MMPs are up-regulated in numerous conditions affecting the vasculature and often exacerbate vascular dysfunction. A growing body of evidence supports the rationale of using MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic vascular dementia. This manuscript will examine promising targets for MMP inhibition in atherosclerosis and stroke, reviewing findings in preclinical animal models and human patient studies. Strategies for MMP inhibition have progressed beyond chelating the catalytic zinc to functional blocking antibodies and peptides that target either the active site or exosites of the enzyme. While the inhibition of MMP activity presents a rational therapeutic avenue, the multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors that cause unintended side-effects hinder full realization of MMP inhibition as therapy for vascular disease. For optimal therapeutic effects to be realized, specific targets for MMP inhibition in these pathologies must first be identified and then attacked by potent and selective agents during the most appropriate timepoint.

  3. Noninvasive indicators of atherosclerosis in subclinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    Ismail Dogu Kilic

    2013-01-01

    Full Text Available Introduction: Cardiovascular system is rich in thyroid hormone receptors and is one of the major sites of action for thyroid hormones. However, the effect of subclinical hypothyroidism (SCH on atherosclerosis has not been cleared yet. Materials and Methods: SCH is defined as high thyroid-stimulating hormone (TSH levels in the presence of normal serum T4 and T3 levels. A total of 32 patients with SCH and 29 controls were included in the study. Carotid intima-media thickness, flow-mediated dilatation, and aortic distensibility were compared between the groups. Results: FMD was lower in patients with SCH than in controls. GTN-induced vasodilatation was similar in the patients with SCH and controls. There was no statistically significant difference between the patients with SCH and controls with respect to CIMT and aortic distensibility. Conclusion: SCH is associated with endothelial dysfunction as established by FMD. Inconsistent results of CIMT and aortic stiffness can be explained by these parameters being measures of structural changes whereas FMD is a dynamic measure that reflects the impact of both acute and chronic influences on endothelial function.

  4. Is Sudden Hearing Loss Associated with Atherosclerosis?

    Directory of Open Access Journals (Sweden)

    Mohsen Rajati

    2016-05-01

    Full Text Available Introduction: Sudden sensorineural hearing-loss (SSNHL patients constitute approximately 2–3% of referrals to ear, nose and throat (ENT clinics. Several predisposing factors have been proposed for this condition; one of which is vascular disorders and perfusion compromise. In this research the atherosclerotic changes and their known risk factors are studied in SSNHL patients.   Materials and Methods: Thirty SSNHL patients and 30 controls were evaluated with regard to cardiovascular risks including history, heart examination, blood pressure, body mass index, waist circumference, electrocardiogram, blood sugar, triglycerides, cholesterol, high-sensitivity C-reactive protein (HSCRP; also, carotid artery color Doppler study was undertaken to measure intima media thickness(IMT.   Results: IMT and HSCRP showed an increased risk in the case group compared with the controls (P= 0.005 & P=0.001. However, waist circumference, history of smoking, fasting blood sugar, lipid profile, and electrocardiogram revealed no significant difference between the two groups. Interestingly, blood pressure and body mass index were higher in the controls in this study.   Conclusion:  Sudden sensorineural hearing loss may be associated with subclinical atherosclerosis.

  5. Is Sudden Hearing Loss Associated with Atherosclerosis?

    Science.gov (United States)

    Rajati, Mohsen; Azarpajooh, Mahmoud Reza; Mouhebati, Mohsen; Nasrollahi, Mostafa; Salehi, Maryam; Khadivi, Ehsan; Nourizadeh, Navid; Hashemi, Firoozeh; Bakhshaee, Mehdi

    2016-01-01

    Introduction: Sudden sensorineural hearing-loss (SSNHL) patients constitute approximately 2–3% of referrals to ear, nose and throat (ENT) clinics. Several predisposing factors have been proposed for this condition; one of which is vascular disorders and perfusion compromise. In this research the atherosclerotic changes and their known risk factors are studied in SSNHL patients. Materials and Methods: Thirty SSNHL patients and 30 controls were evaluated with regard to cardiovascular risks including history, heart examination, blood pressure, body mass index, waist circumference, electrocardiogram, blood sugar, triglycerides, cholesterol, high-sensitivity C-reactive protein (HSCRP); also, carotid artery color Doppler study was undertaken to measure intima media thickness(IMT). Results: IMT and HSCRP showed an increased risk in the case group compared with the controls (P= 0.005 & P=0.001). However, waist circumference, history of smoking, fasting blood sugar, lipid profile, and electrocardiogram revealed no significant difference between the two groups. Interestingly, blood pressure and body mass index were higher in the controls in this study. Conclusion: Sudden sensorineural hearing loss may be associated with subclinical atherosclerosis. PMID:27429947

  6. Research Advances of Atherosclerosis in Translational Medicine

    Institute of Scientific and Technical Information of China (English)

    YANG Zhuo-xin; DENG Rong; PI Min; YU Hai-bo

    2015-01-01

    Atherosclerotic cardiovascular diseases (ASCVD) are defined as a series of diseases caused by atherosclerosis (AS), including coronary heart disease (CHD), myocardial infarction (MI), stable or unstable angina pectoris, revascularization of coronary artery or other arteries, stroke, transient cerebral ischemic onset or atherosclerotic peripheral arterial disease. AS has common pathological basis with ASCVD as it is a general arterial regressive disease of human beings. With the industrialization progression, AS morbidity increases annually and it also leads to coronary atherosclerotic heart disease, cerebral stroke and peripheral artery stenosed occlusion or dilation, thus becoming the main cause for high disability and mortality. The main purpose of translational medicine is to break the intrinsic barrier between basic medicine with drug research and development as well as clinical and public healthcare, and establish a direct connection between them. It is also can rapidly transform basic research results to new clinical preventive and therapeutic methods. This study mainly reviewed AS from the aspect of translational medicine, aiming to provide a reliable basis for the prevention and treatment of AS.

  7. Atherosclerosis: from biology to pharmacological treatment

    Institute of Scientific and Technical Information of China (English)

    Graziano Riccioni; Valeriana Sblendorio

    2012-01-01

    A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.

  8. Hostility, Anger and Risk of Coronary Artery Atherosclerosis

    Directory of Open Access Journals (Sweden)

    E Masoudnia

    2011-02-01

    Full Text Available Introduction: The previous researches about the etiology of coronary artery atherosclerosis have accentuated on clinical and medical risk factors, such as cigarette smoking, hypertension, diabetes mellitus, hyperlipidemia, positive family background, myocardial ischemia history in family, atherogenic diet, increase of A lipoprotein, inflammatory factors such as increase of cross-reactive protein and so on. Although factors in behavioral medicine are recognized as an independent risk factor in coronary artery atherosclerosis, few researches have been done on hostility and anger. The aim of this study was to determine the difference between normal people(Control group and people with coronary artery atherosclerosis(Case group with regards to hostility and anger. Methods: This study was performed as a case-control design. Data was collected from seventy-seven patients with coronary artery atherosclerosis who had referred to Afshar Hospital Professional Heart Clinic in Yazd city and seventy-eight normal people were used as control. Two groups completed the Buss and Perry Aggression Questionnaire(BPAQ to measure their hostility and anger. Results: The results of the analysis showed that there was a statistically significant difference regarding hostility(p<.05 and anger(p<.001 between the two groups. Hierarchical multiple logistic regression analysis showed that the sociodemographic and clinical variables(step 1 explained 35.5 % to 47.4%, while hostility and anger(step 2 explained 6.7% to 9% of the variance in incidence of coronary artery atherosclerosis. Conclusion: Hostility and anger are strong risk factors for coronary artery atherosclerosis or CAD in Iran. Therefore, in order to decrease the incidence rate of coronary artery atherosclerosis in Iran, alongside medical interventions, attention should also be paid towards behavioral interventions in order to modify hostile and angrily behavior.

  9. Immune mechanisms in atherosclerosis, especially in diabetes type 2.

    Science.gov (United States)

    Frostegård, Johan

    2013-10-29

    Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1β (IL-1β), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed.

  10. MicroRNAs in Lipid Metabolism and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-04-01

    Full Text Available BACKGROUND: MicroRNAs (miRNA are mediators of post-transcriptional gene expression that likely regulate most biological pathways and networks. The study of miRNAs is a rapidly emerging field; recent findings have revealed a significant role for miRNAs in atherosclerosis and lipoprotein metabolism. CONTENT: Results from recent studies demonstrated a role for miRNAs in endothelial integrity, macrophage inflammatory response to oxidized low-density lipoprotein, vascular smooth muscle cell proliferation and cholesterol synthesis. These mechanisms are all vital to the initiation and proliferation of atherosclerosis and cardiovascular disease. The importance of miRNAs has recently been recognized in cardiovascular sciences and miRNAs will likely become an integral part of our fundamental comprehension of atherosclerosis and lipoprotein metabolism. The extensive impact of miRNA mediated gene regulation and the relative ease of in vivo applicable modifications highlight the enormous potential of miRNA-based therapeutics in cardiovascular diseases. SUMMARY: miRNA studies in the field of lipid metabolism and atherosclerosis are in their infancy, and thus there is tremendous opportunity for discovery in this understudied area. The ability to target miRNAs in vivo through delivery of miRNA-mimics to enhance miRNA function, or antimiRNAs which inhibit miRNAs, has opened new avenues for the development of therapeutics for dyslipidemias and atherosclerosis, offers a unique approach to treating disease by modulating entire biological pathways. These exciting findings support the development of miRNA antagonists as potential therapeutics for the treatment of dyslipidaemia,atherosclerosis and related metabolic diseases. KEYWORDS: atherosclerosis, lipoprotein, HDL, miRNA.

  11. Ultrasound screening of multifocal atherosclerosis: markers for coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Lachezar Grozdinski; Mario Stankev; Alexander Doganov

    2009-01-01

    Background and Objective The frequency of multifocal atherosclerosis (MFA) in patients with coronary heart disease (CHD) has not been thoroughly studied. The purpose of our study was to perform ultrasound screening for MFA in patients with coronary atherosclerosis and make evaluation of the sensitivity and significance of different atherosclerosis markers. Methods Using Color Dupplex Ultrasound (CDU), we studied 32 clinically healthy persons and 87 patients of the city of B with clinical data for CHD where we also performed coronarography. Results In patients with coronary atherosclerosis we found high frequency of carotid atherosclerosis (93%) and peripheral artery disease (PAD) (81%). We established verifiable thickening of the intima-media (IMT) of the common carotid artery (CCA) and common femoral artery (CFA) in patients with CHD. There is a correlation between the frequency of carotid and femoral stenoses and CHD proven by coronarography. Patients with CHD had a high relative risk to develop carotid (RR = 5) and peripheral atherosclerosis (RR=3.5) and high frequency of asymptomatic stenoses and thromboses of the internal carotid artery (86.9%) and femoral artery (78.3%), as well as aneurisms of the abdominal aorta (8.1%). Markers for CAD with high sensitivity were the atherosclerotic plaques of ICA (0.93) and CFA (0.81) as well as IMT of the CFA (0.84). Conclusions MFA are common among patients with CHD. Ultrasound diagnosis is the method of choice for simultaneous non-invasive screening of carotid, peripheral and MFA and provides sensitive markers for coronary atherosclerosis. The most sensitive and specific markers for CHD are the combination of the IMT and atherosclerotic plaques of CCA, ICA and CFA (100% sensitivity and 0.92 specificity).

  12. Apolipoprotein E gene polymorphisms as risk factors for carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zurnić Irena

    2014-01-01

    Full Text Available Background/Aim. Atherosclerosis is still the leading cause of death in Western world. Development of atherosclerotic plaque involves accumulation of inflammatory cells, lipids, smooth muscle cells and extracellular matrix proteins in the intima of the vascular wall. Apolipoprotein E participates in the transport of exogenous cholesterol, endogenouly synthesized lipids and triglycerides in the organism. Apolipoprotein E gene has been identified as one of the candidate genes for atherosclerosis. Previous studies in different populations have clearly implicated apolipoprotein E genetic variation (ε polymorphisms as a major modulator of low density lipoprotein cholesterol levels. Data considering apolipoprotein E polymorphisms in relation to carotid atherosclerosis gave results that are not in full compliance. The aim of present study was to investigate the apolipoprotein E polymorphisms in association with carotid plaque presence, apolipoprotein E and lipid serum levels in patients with carotid atherosclerosis from Serbia. Methods. The study group enrolled 495 participants: 285 controls and 210 consecutive patients with carotid atherosclerosis who underwent carotid endarterectomy. Genotyping of apolipoprotein E polymorphisms were done using polymerase chain reaction and restriction fragment length polymorphism methods. Results. Patients had significantly decreased frequency of the ε2 allele compared to controls. Patients who carry at least one ε2 allele had a significantly higher level of serum apolipoprotein E and significantly lower low density lipoprotein cholesterol levels compared to those who do not carry this allele. Conclusion. Our results suggest protective effect of apolipoprotein E ε2 allele on susceptibility for carotid plaque presence as well as low density lipoprotein cholesterol lowering effect in Serbian patients with carotid atherosclerosis. Further research of multiple gene and environmental factors that contribute to the

  13. Association Between Psoriasis and Subclinical Atherosclerosis

    Science.gov (United States)

    Fang, Na; Jiang, Menglin; Fan, Yu

    2016-01-01

    Abstract The association between psoriasis and carotid intima-media thickness (CIMT) or impaired flow-mediated dilation (FMD) remains controversial. We aimed to evaluate the extent of subclinical atherosclerosis as measured by CIMT and FMD in patients with psoriasis by conducting a meta-analysis. A systematic literature search was performed using PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure, and VIP databases up to February 2015. Observational studies investigating CIMT or FMD in patients with psoriasis and controls were eligible. Psoriatic patients and controls were at least age- and sex-matched. Random-effects analysis was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI) between psoriatic patients and controls. A total of 20 studies were identified and analyzed. Meta-analysis showed that psoriatic patients had a significantly thicker CIMT (WMD 0.11 mm; 95% CI 0.08–0.15) and lower FMD (WMD −2.79%; −4.14% to −1.43%) than those in controls. Subgroup analysis indicated that psoriatic arthritis appeared to have less impaired FMD (WMD −2.45%) and thinner CIMT (WMD 0.10 mm). Psoriatic patients with mean age >45 years had much thicker CIMT (WMD 0.13 mm). The impaired FMD (WMD −3.99%) seemed more pronounced in psoriatic patients with mean age FMD may be recommended to identify a subgroup of psoriatic patients at higher risk for cardiovascular events. PMID:27196459

  14. Effects of ezetimibe on atherosclerosis in preclinical models.

    Science.gov (United States)

    Davis, Harry R; Lowe, Robert S; Neff, David R

    2011-04-01

    Ezetimibe (Zetia(®), Ezetrol(®), Merck, Whitehouse Station, NJ) is a potent inhibitor of sterol absorption, which selectively blocks the uptake of biliary and dietary cholesterol in the small intestine. Clinical trials have demonstrated the beneficial effects of ezetimibe on the reduction of atherogenic lipoproteins and the attainment of guideline-recommended lipid levels. Direct evidence that these improvements translate to a reduction in atherosclerosis or cardiovascular events is limited, although reductions in major atherosclerotic events that are consistent with the LDL-C lowering achieved have recently been presented for patients with chronic kidney disease treated with ezetimibe/simvastatin 10/20mg in the SHARP trial. Animal models of atherosclerosis have played a central role in defining the mechanisms involved in initiation and development of disease and have been used in drug development to evaluate potential therapeutic efficacy. The effect of ezetimibe on atherosclerosis has been examined in several of these animal model systems. ApoE knockout mice develop severe hypercholesterolemia and premature atherosclerosis with features similar to that seen in humans and techniques ranging from gross visualization of plaque to high-resolution MRI have demonstrated the consistent ability of ezetimibe to significantly inhibit atherosclerosis. sr-b1(-/-)/apoE(-/-) double knockout mice exhibit additional characteristics common to human coronary heart disease (CHD), and the one study of ezetimibe in sr-b1(-/-)/apoE(-/-) mice showed a significant reduction in aortic sinus plaque (57%), coronary arterial occlusion (68%), myocardial fibrosis (57%), and cardiomegaly (12%) compared with untreated controls. The effects of ezetimibe have also been evaluated in ldlr(-/-)/apoE(-/-) double knockout mice, demonstrating that functional LDL receptors were not required for ezetimibe-mediated reduction of plasma cholesterol or atherosclerosis. For the few studies that have been

  15. Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis

    Science.gov (United States)

    Babaev, Vladimir R.; Chew, Joshua D.; Ding, Lei; Davis, Sarah; Breyer, Matthew D.; Breyer, Richard M.; Oates, John A.; Fazio, Sergio; Linton, MacRae F.

    2009-01-01

    Prostagladin (PG) E2, a major product of activated macrophages, has been implicated in atherosclerosis and plaque rupture. The PGE2 receptors, EP2 and EP4, are expressed in atherosclerotic lesions and are known to inhibit apoptosis in cancer cells. To examine the roles of macrophage EP4 and EP2 in apoptosis and early atherosclerosis, fetal liver cell transplantation was used to generate LDLR−/− mice chimeric for EP2−/− or EP4−/− hematopoietic cells. After 8-weeks on a Western diet, EP4−/− → LDLR−/− mice, but not EP2−/− → LDLR−/− mice, had significantly reduced aortic atherosclerosis with increased apoptotic cells in the lesions. EP4−/− peritoneal macrophages had increased sensitivity to pro-apoptotic stimuli, including palmitic acid and free cholesterol loading, which was accompanied by suppression of activity of p-Akt, p-Bad and NF-kB-regulated genes. Thus, EP4 deficiency inhibits the PI3K/Akt and NF-kB pathways compromising macrophage survival and suppressing early atherosclerosis, identifying macrophage EP4 signaling pathways as molecular targets for modulating the development of atherosclerosis. PMID:19041765

  16. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Suppression of atherosclerosis by synthetic REV-ERB agonist

    International Nuclear Information System (INIS)

    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

  18. IL-35: a potential target for the treatment of atherosclerosis.

    Science.gov (United States)

    Huang, Ying; Lin, Ying-Zhong; Shi, Ying; Ji, Qing-Wei

    2013-10-01

    The imbalance of anti- inflammatory/pro-inflammatory cytokines plays an important role in the process of atherosclerosis. IL-35 is an anti-inflammatory cytokine comprising the p35 subunit of IL-12 and the subunit Epstein-Barr virus (EBV) -induced gene 3(EBI3). Accumulating evidence showed that IL-35 up-regulates the expression of anti-inflammatory cytokines, induces the generation of CD4 + regulatory T cells, inhibits CD4 + effector T cells response and other target cells activity, and reduces the progression of inflammatory and autoimmune diseases. In addition, it has been found that Ebi3 and p35 strongly coexpressed in human advanced lesions. Therefore, we hypothesize that IL-35 may become a novel target for the treatment of atherosclerosis. Further studies are required to investigate the precise effect and the signaling pathway of IL-35 in atherosclerosis process.

  19. Redox balance and blood elemental levels in atherosclerosis

    Science.gov (United States)

    Napoleão, P.; Lopes, P. A.; Santos, M.; Steghens, J.-P.; Viegas-Crespo, A. M.; Pinheiro, T.

    2006-08-01

    Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant (α-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

  20. Nestin(+) cells direct inflammatory cell migration in atherosclerosis.

    Science.gov (United States)

    Del Toro, Raquel; Chèvre, Raphael; Rodríguez, Cristina; Ordóñez, Antonio; Martínez-González, José; Andrés, Vicente; Méndez-Ferrer, Simón

    2016-01-01

    Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) cells-but not in endothelial cells only- increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis. PMID:27586429

  1. Immunometabolism of AMPK in insulin resistance and atherosclerosis.

    Science.gov (United States)

    Fullerton, Morgan D; Steinberg, Gregory R; Schertzer, Jonathan D

    2013-02-25

    Obesity leads to insulin resistance and atherosclerosis, which precede Type 2 diabetes and cardiovascular disease. Immunometabolism addresses how metabolic and inflammatory pathways converge to maintain health and a contemporary problem is determining how obesity-induced inflammation precipitates chronic diseases such as insulin resistance and atherosclerosis. AMP-activated protein kinase (AMPK) is an important serine/threonine kinase well known for regulating metabolic processes and maintaining energy homeostasis. However, both metabolic and immunological AMPK-mediated effects play a role in disease. Pro-inflammatory mediators suppress AMPK activity and hinder lipid oxidation. In addition, AMPK activation curbs inflammation by directly inhibiting pro-inflammatory signaling pathways and limiting the build-up of specific lipid intermediates that elicit immune responses. In the context of obesity and chronic disease, these reciprocal responses involve both immune and metabolic cells. Therefore, the immunometabolism of AMPK-mediated processes and therapeutics should be considered in atherosclerosis and insulin resistance. PMID:22361321

  2. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

    International Nuclear Information System (INIS)

    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 (H2S), 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 H2S and inflammatory processes. The role of H2S 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 H2S in atherosclerosis.

  3. Redox balance and blood elemental levels in atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Napoleao, P. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal) and Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal)]. E-mail: pnapoleao@itn.pt; Lopes, P.A. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Santos, M. [Centro de Quimica e Bioquimica and Departamento de Quimica e Bioquimica, Faculdade de Ciencias de Lisboa, 1749-016 Lisbon (Portugal); Steghens, J.-P. [Federation de Biochimie, Hopital Edouard Herriot, 3 Place d' Arsonval, 69437 03 Lyon (France); Viegas-Crespo, A.M. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Pinheiro, T. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal); Centro de Fisica Nuclear, Universidade de Lisboa, Av. Prof. Egas Moniz, 1700 Lisbon (Portugal)

    2006-08-15

    Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant ({alpha}-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

  4. Role of Helicobacter pylori infection in pathogenesis of atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Rajesh; Vijayvergiya; Ramalingam; Vadivelu

    2015-01-01

    Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.

  5. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Wang [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Chaoshu, Tang [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China); Key Laboratory of Molecular Cardiovascular Medicine, Ministry of Education (China); Hongfang, Jin, E-mail: jinhongfang51@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Junbao, Du, E-mail: junbaodu1@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)

    2010-05-28

    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{sub 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{sub 2}S and inflammatory processes. The role of H{sub 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{sub 2}S in atherosclerosis.

  6. 75 FR 62544 - Proposed Collection; Comment Request; the Atherosclerosis Risk in Communities Study (ARIC)

    Science.gov (United States)

    2010-10-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; the Atherosclerosis... and Budget (OMB) for review and approval. Proposed Collection: Title: The Atherosclerosis Risk...

  7. 75 FR 7482 - Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC)

    Science.gov (United States)

    2010-02-19

    ... Atherosclerosis Risk in Communities Study (ARIC) Summary: Under the provisions of Section 3507(a)(1)(D) of the... Title: The Atherosclerosis Risk in Communities Study (ARIC). Type of Information Collection...

  8. 76 FR 3146 - Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC)

    Science.gov (United States)

    2011-01-19

    ... Atherosclerosis Risk in Communities Study (ARIC) Summary: Under the provisions of Section 3507(a)(1)(D) of the...: Title: The Atherosclerosis Risk in Communities Study (ARIC). Type of Information Collection...

  9. A pilot study into measurements of markers of atherosclerosis in periodontitis

    NARCIS (Netherlands)

    Leivadaros, E; van der Velden, U; Bizzarro, S; ten Heggeler, JMAG; Gerdes, VEA; Hoek, FJ; Nagy, TOM; Scholma, J; Bakker, SJL; Gans, ROB; ten Cate, H; Loos, BG

    2005-01-01

    Background: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. Methods: Patients with moderate (N = 34) and severe periodonti

  10. Potential cell-specific functions of CXCR4 in atherosclerosis.

    Science.gov (United States)

    Weber, Christian; Döring, Yvonne; Noels, Heidi

    2016-05-10

    The chemokine CXCL12 and its receptor CXCR4 form an important axis contributing to cellular functions in homeostasis and disease. In addition, the atypical CXCL12 receptor CXCR7 may shape the availability and function of CXCL12. Further to their role through progenitor cell mobilization, CXCL12 and CXCR4 may affect native atherogenesis by modifying atherosclerosis-relevant cellular functions. This short review intends to provide a concise summary of current knowledge with regards to cell-specific functions of CXCL12 and its receptors CXCR4 and CXCR7 with potential implications for the initiation and progression of atherosclerosis. PMID:25586789

  11. Increased YKL-40 expression in patients with carotid atherosclerosis

    DEFF Research Database (Denmark)

    Michelsen, Axel Gottlieb; Rathcke, C.N.; Skjelland, M.;

    2010-01-01

    atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...

  12. Stanniocalcin-2 overexpression reduces atherosclerosis in hypercholesterolemic mice

    DEFF Research Database (Denmark)

    Steffensen, Lasse B; Conover, Cheryl A; Bjørklund, Martin M;

    2016-01-01

    lesion development. We then used adeno-associated virus-mediated expression of STC2 to increase the fraction of PAPP-A present in the inhibited state and found that it decreased the development of atherosclerosis by 47% (P = 0.0005) in apolipoprotein E-deficient mice challenged with a Western type diet...... compared to controls. CONCLUSIONS: This study is the first to suggest the involvement of STC2 in regulating PAPP-A activity during the development of atherosclerosis. Furthermore, we demonstrate that lesion development can be inhibited in an experimental model by driving the balance towards inhibited PAPP-A....

  13. Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders

    OpenAIRE

    Elisabetta Profumo; Manuela Di Franco; Brigitta Buttari; Roberta Masella; Carmelina Filesi; Maria Elena Tosti; Rossana Scrivo; Antongiulio Scarno; Antonio Spadaro; Luciano Saso; Rachele Riganò

    2012-01-01

    Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and β -carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and I...

  14. Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

    DEFF Research Database (Denmark)

    Bang, Christian A; Bro, Susanne; Bartels, Emil D;

    2007-01-01

    Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

  15. DMPD: Toll-like receptors in atherosclerosis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031244 Toll-like receptors in atherosclerosis. Tobias PS, Curtiss LK. Biochem Soc... Trans. 2007 Dec;35(Pt 6):1453-5. (.png) (.svg) (.html) (.csml) Show Toll-like receptors in atherosclerosis.... PubmedID 18031244 Title Toll-like receptors in atherosclerosis. Authors Tobias PS, Curtiss LK. Publication

  16. 75 FR 46945 - Proposed Collection; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...

    Science.gov (United States)

    2010-08-04

    ... Atherosclerosis (MESA) Event Surveillance SUMMARY: In compliance with the requirement of Section 3506(c)(2)(A) of... Budget (OMB) for review and approval. Proposed Collection: Title: Multi-Ethnic Study of Atherosclerosis... and progression of subclinical cardiovascular disease (CVD)-- that is, atherosclerosis and other...

  17. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

    NARCIS (Netherlands)

    Berbeé, J.F.P.; Boon, M.R.; Khedoe, P.P.S.J.; Bartelt, A.; Schlein, C.; Worthmann, A.; Kooijman, S.; Hoeke, G.; Mol, I.M.; John, C.; Jung, C.; Vazirpanah, N.; Brouwers, L.P.J.; Gordts, P.L.S.M.; Esko, J.D.; Hiemstra, P.S.; Havekes, L.M.; Scheja, L.; Heeren, J.; Rensen, P.C.N.

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic rece

  18. Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs

    Directory of Open Access Journals (Sweden)

    Thim Troels

    2012-03-01

    Full Text Available Abstract Background Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis. Methods An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs. The vein grafts were investigated 12-14 weeks later with ultrasound and angiograpy in vivo and microscopy post mortem. Results One minipig died during follow up (patent vein graft at autopsy, and one vein graft thrombosed early. In the remaining eight patent vein grafts, the mean (standard deviation intima-media thickness was 712 μm (276 μm versus 204 μm (74 μm in the contralateral control internal jugular veins (P diameter of artery. No plaques were found in four non-oversized vein grafts (P Conclusions Our model of jugular vein graft in the common carotid artery of hypercholesterolemic minipigs displayed the components of human vein graft disease, i.e. thrombosis, intimal hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of late failure of human aortocoronary vein grafts was only seen in oversized grafts. This finding suggests that oversized vein grafts may have detrimental effects on patient outcome.

  19. Atherosclerosis induced by diabetogenic diet in New Zealand white rabbits

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To observe the effects of diabetogenic (high fat high sucrose, lacking choleserol) diet on atherogenesis in New Zealand white rabbits. Two groups of New Zealand white rabbits received regular rabbit chow (the normal control), or high fat high sucrose diet for 4 months. The levels of plasma total cholesterol, HDL cholesterol, triglycerides, insulin, and glucose were investigated, the areas of fatty streak of the aortae were measured after staining with Sodan IV, and the aortic, coronary specimens were observed with light and electron microscopies. The plasma glucose, triglycerides, and total cholesterol were increased significantly by high fat high sucrose feeding. At the end of 4 months, the early charateristics of atherosclerosis were present in the animals' vascular specimens. Our findings suggest that high fat high sucrose feeding can induce hyperglycemia, hypertriglyceridemia and atherosclerosis in New Zealand white rabbits, and this could be a potential animal model for studying the mechanisms of diabetes-accelerated atherosclerosis. This study raised a question: What is the mechanism by which high fat high sucrose feeding induces atherosclerosis?. The related hypothesis was given in this article.

  20. Venous Thrombosis and Atherosclerosis is There a link

    Institute of Scientific and Technical Information of China (English)

    LIU MIN-JUAN; LiU Ze-lin

    2008-01-01

    @@ Venous thrombosis and arterial thrombotic disorders have long been viewed as separate pathophysiological entities, partly as a result of the obvious anatomical differences, as well as their distinct clinical presentations. Recently, the potential association between venous thromboembolism(VTE) and atherosclerosis was described for the first time in 2003. Subsequently, numerous investigations have addressed the topic.

  1. Recent advances in lipoprotein and atherosclerosis: nutrigenomic approach

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, S.; Ortega, A.; Varela, L.; Bermudez, B.; Muriana, F. J. G.; Abaia, R.

    2009-07-01

    Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing omics techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall. (Author) 55 refs.

  2. Proteomic identification of proteins in exosomes of patients with atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    JIANG Mei; QUAN Jing; ZHANG Heng; DING Qian-qian; XIANG Meng; MENG Dan; SUN Ning; CHEN Si-feng

    2016-01-01

    AIM:Atherosclerosis primarily involved systemic arteries .Luminal surface , a monolayer of endothelial cells , of artery directly exposes to blood and is susceptible to active substances in the blood .Exosomes contain significantly amount of proteins and RNAs .Ex-osomes can be good and bad for cells , depending on their component .Thus, exosomes may contribute to atherosclerosis by affecting endothelial cells .This study analyzed the relationship of exosome proteins and atherosclerosis .METHODS: Fifty-six patients and healthy subjects were recruited and divided into two comparisons:healthy subjects vs atherosclerosis ( HS vs AS) , and hypertension vs hypertension plus atherosclerosis ( HT vs HT+AS) .Serum exosomes were decoded by protein mass spectrometry .The protein profile and function were analyzed by gene ontology ( GO) .RESULTS:It was found that five child terms repeatedly appeared in “response to stimulus” and “immune system process” of BP of the two categories ( HS vs AS and AS vs HT+AS):“positive regulation of innate immune response”,“immune response-activating signal transduction”,”activation of innate immune response”,“innate immune re-sponse-activating signal transduction” and “innate immune response activating cell surface receptor signaling pathway ”.Two child terms repeatedly showed in “binding” of MF of the two categories:“antigen binding” and “enzyme binding”.Two proteins, PSMA6 and PSMA7, were repeatedly shown in the two categories .CONCLUSION:GO analysis was utilized for structure hierarchy “tree” to illustrate these proteins involved in various terms in BP , CC and MF.The PPI analysis supplied proteins which may play potentially im-portant roles in AS process .Innate immune system and blood coagulation pathway contribute to AS formation .The proteins, PSMA6, PSMA7 and Annexin A2, may can be the new target proteins for prevention and treatment of AS .

  3. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  4. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

    Science.gov (United States)

    Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

    2016-03-01

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

  5. Prevention and treatment of atherosclerosis with flaxseed-derived compound secoisolariciresinol diglucoside.

    Science.gov (United States)

    Prasad, Kailash; Jadhav, Ashok

    2016-01-01

    Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease

  6. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis.

    Science.gov (United States)

    Kojima, Yoko; Volkmer, Jens-Peter; McKenna, Kelly; Civelek, Mete; Lusis, Aldons Jake; Miller, Clint L; Direnzo, Daniel; Nanda, Vivek; Ye, Jianqin; Connolly, Andrew J; Schadt, Eric E; Quertermous, Thomas; Betancur, Paola; Maegdefessel, Lars; Matic, Ljubica Perisic; Hedin, Ulf; Weissman, Irving L; Leeper, Nicholas J

    2016-08-01

    Atherosclerosis is the disease process that underlies heart attack and stroke. Advanced lesions at risk of rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Why these cells are not cleared remains unknown. Here we show that atherogenesis is associated with upregulation of CD47, a key anti-phagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or 'efferocytosis'. We find that administration of CD47-blocking antibodies reverses this defect in efferocytosis, normalizes the clearance of diseased vascular tissue, and ameliorates atherosclerosis in multiple mouse models. Mechanistic studies implicate the pro-atherosclerotic factor TNF-α as a fundamental driver of impaired programmed cell removal, explaining why this process is compromised in vascular disease. Similar to recent observations in cancer, impaired efferocytosis appears to play a pathogenic role in cardiovascular disease, but is not a fixed defect and may represent a novel therapeutic target. PMID:27437576

  7. Novel anti-inflammatory therapies for the treatment of atherosclerosis.

    Science.gov (United States)

    Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L

    2015-06-01

    The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels.

  8. Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

    OpenAIRE

    Maiseyeu, Andrei; Mihai, Georgeta; Kampfrath, Thomas; Simonetti, Orlando P.; Sen, Chandan K.; Roy, Sashwati; Rajagopalan, Sanjay; Parthasarathy, Sampath

    2009-01-01

    Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellula...

  9. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Kazim; Husain; Wilfredo; Hernandez; Rais; A; Ansari; Leon; Ferder

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

  10. Improved Animal Models for Testing Gene Therapy for Atherosclerosis

    OpenAIRE

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R. Y.; Flynn, Rowan; Dichek, David A.

    2013-01-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike le...

  11. Nikolai N. Anichkov and His Theory of Atherosclerosis

    OpenAIRE

    Konstantinov, Igor E.; Mejevoi, Nicolai; Anichkov, Nikolai M.

    2006-01-01

    Nikolai N. Anichkov (1885–1964) first demonstrated the role of cholesterol in the development of atherosclerosis. His classic experiments in 1913 paved the way to our current understanding of the role of cholesterol in cardiovascular disease. Anichkov's research is often cited among the greatest discoveries of the 20th century; however, little is known about Anichkov and his team. Herein, we give a detailed historical account of Anichkov's work, his personality, his research team, and their p...

  12. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  13. Regulatory role of mitochondria in oxidative stress and atherosclerosis

    OpenAIRE

    Chang, Jui-Chih; Kou, Shou-Jen; Lin, Wei-Ting; Liu, Chin-San

    2010-01-01

    Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis (AST). Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species (ROS) production, accumulation of mitochondrial DNA damage, and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial ...

  14. Effects of intra-abdominal sepsis on atherosclerosis in mice

    OpenAIRE

    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.

    2014-01-01

    Introduction 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. Methods 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 ...

  15. Association between Metabolic Components and Subclinical Atherosclerosis in Korean Adults

    OpenAIRE

    Hwang, In Cheol; Suh, Sang-Yeon; Seo, Ah-Ram; Ahn, Hong Yup; Yim, Eunji

    2012-01-01

    Background Many studies have attempted to develop relatively simple and easy noninvasive measurements of atherosclerosis (NIMA), and each NIMA assesses different atherosclerotic properties. We, therefore, investigated the association between metabolic syndrome (MetS) components and different NIMAs. Methods This study included 1,132 Korean subjects over 20 years of age who had visited a Health Promotion Center in Korea. Carotid injury (increased carotid intima-media thickness or plaques) was e...

  16. Bisphenol A exposure enhances atherosclerosis in WHHL rabbits.

    Directory of Open Access Journals (Sweden)

    Chao Fang

    Full Text Available Bisphenol A (BPA is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs and rabbit aortic smooth muscle cells (SMCs with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s. BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37% accompanied by smooth muscle cells (60% but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits.

  17. Association between atherosclerosis and osteoporosis, the role of vitamin D

    OpenAIRE

    Stojanovic, Olivera Ilić; Lazovic, Milica; Lazovic, Marko; Vuceljic, Marina

    2011-01-01

    The latest data support the correlation of atherosclerosis and osteoporosis, indicating the parallel progression of two tissue destruction processes with increased fatal and non-fatal coronary events, as well as higher fracture risk. Vitamin D inadequacy associated with low bone mineral density increases fall and fracture risk, leads to secondary hyperparathyroidism, calcifies coronary arteries and significantly increases cardiovascular disease. Randomized clinical trial evidence related to e...

  18. Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Elisabetta Profumo

    2012-01-01

    Full Text Available Atherosclerosis is accelerated in rheumatoid arthritis (RA and psoriatic arthritis (PsA. We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs, nitric oxide (NO, 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.

  19. Single low shear stress results in atherosclerosis in vivo

    Institute of Scientific and Technical Information of China (English)

    HUANG Rong-guo; LIU Hou-qi; YANG Xiang-qun; ZHANG Chuan-sen; KANG Bin; JIANG Zong-lai

    2005-01-01

    Objective: Whether single low shear stress can result in atherosclerosis without hyperliposis-diet in vivo or not is unknown. Methods: Based on an electromagnetic blood flow meter and a method to determine the pulsatile shear stress from blood flow rate waveform and its software,we developed an in vivo pulsatile blood flow rate-shear stress determining system.The left external carotid arteries of 20 adult New Zealand white rabbits were ligated and the rabbits were fed with a standard chow for 2,4,8 or 12 weeks,then the common carotid arteries of 2 sides in each rabbit were harvested for morphologic test. Results: The ligation reduced pulsatile shear stress of left common carotid significantly,for example,τmean changed from(21.16±7.17) dynes/cm2 to(3.13±2.28) dynes/cm2(p=2.176E-21),meanwhile,the pulsatile shear stress of right common carotid did not change significantly,which lasted more than 12 weeks.Atherosclerotic plaques were found after 8 and 12 weeks in pulsatile-low-shear-stress left(not normal-shear-stress right) common carotid arteries.Conclusion:Single pulsatile low shear stress can result in atherosclerosis.It supports the pulsatile low shear stress(not hypolipidemia) is the key risk factor for atherosclerosis.

  20. SIRT6 protects against endothelial dysfunction and atherosclerosis in mice

    Science.gov (United States)

    Xu, Suowen; Yin, Meimei; Koroleva, Marina; Mastrangelo, Michael A.; Zhang, Wenbo; Bai, Peter; Little, Peter J.; Jin, Zheng Gen

    2016-01-01

    SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE−/− mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation. Moreover, SIRT6+/− haploinsufficient mice fed a high-fat diet (HFD) also displayed impaired endothelium-dependent vasorelaxation. Importantly, SIRT6+/−;ApoE−/− mice after HFD feeding exhibited exacerbated atherosclerotic lesion development, concurrent with increased expression of the proinflammatory cytokine VCAM-1. Loss- and gain-of-SIRT6 function studies in cultured human endothelial cells (ECs) showed that SIRT6 attenuated monocyte adhesion to ECs. RNA-sequencing profiling revealed that SIRT6 overexpression decreased the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4). Chromatin immunoprecipitation assays showed that SIRT6 decreased TNFSF4 gene expression by binding to and deacetylating H3K9 at TNFSF4 gene promoter. Collectively, these findings demonstrate that SIRT6 play a pivotal role in maintaining endothelial function and increased SIRT6 activity could be a new therapeutic strategy to combat atherosclerotic disease. PMID:27249230

  1. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja X; McCormick, Sally P; Tsimikas, Sotirios;

    2010-01-01

    lipoprotein-associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n...... = 19), human apoB-100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo...... with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia....

  2. Biomarkers of subclinical atherosclerosis in patients with autoimmune disorders.

    Science.gov (United States)

    Profumo, Elisabetta; Di Franco, Manuela; Buttari, Brigitta; Masella, Roberta; Filesi, Carmelina; Tosti, Maria Elena; Scrivo, Rossana; Scarno, Antongiulio; Spadaro, Antonio; Saso, Luciano; Riganò, Rachele

    2012-01-01

    Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders. PMID:22529523

  3. Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region

    International Nuclear Information System (INIS)

    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

  4. Atherosclerosis, cholesterol, nutrition, and statins – a critical review

    Directory of Open Access Journals (Sweden)

    Gebbers, Jan-Olaf

    2007-08-01

    Full Text Available Atherosclerosis, which causes approximately half of all deaths of adults over age 60 in industrialized nations, is a pandemic among inappropriately nourished and/or physically hypoactive children, adolescents, and adults world wide. Although nowadays statins are widely prescribed to middle age and elderly adults with high blood lipid levels as pharmacological prevention for the late complications of atherosclerosis, from a critical point of view statins seem not to solve the problem, especially when compared with certain natural ingredients of our nutrition like micronutrients as alternative strategy. Statin ingestion is associated with lowering of serum cholesterol and low-density lipoprotein concentrations; some prospective studies have shown statistical associations with subsequent modest reduction of mortality from cardiovascular disease. However, specific biochemical pathways and pharmacological roles of statins in prevention of atherosclerosis, if any, are unknown. Moreover, there have been no systematic cost-benefit analyses of life-style prophylaxis versus statin prophylaxis versus combined life-style plus statin prophylaxis versus neither life-style nor statin prophylaxis for clinically significant complications of cardiovascular diseases in the elderly. Further, in the trials of effectiveness statins were not compared with management of nutrition, which is the most appropriate alternative intervention. Such studies seem to be important, as the ever increasing world population, especially in developing countries, now demand expensive statins, which may be unaffordable for mitigating the pandemic. Studies of this kind are necessary to identify more precisely those patients for whom cardiovascular benefits will outweigh the risks and costs of the statin treatment in comparison with nutritional interventions. Against the background of the current pathogenetic concept of atherogenesis some of its possible risk factors, particularly the

  5. Atherosclerosis associated with pericardial effusion in a central bearded dragon (Pogona vitticeps).

    Science.gov (United States)

    Schilliger, Lionel; Lemberger, Karin; Chai, Norin; Bourgeois, Aude; Charpentier, Maud

    2010-09-01

    Atherosclerosis is a common disease in pet birds, particularly in psittacines, and is frequently found when performing postmortem examinations on adult and old dogs, in which it is mainly associated with endocrine diseases, such as hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly documented in reptiles and consequently poorly understood. In the current case report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old male central bearded dragon (Pogona vitticeps) based on ultrasound visualization, necropsy, and histologic examination. PMID:20807945

  6. Atherosclerosis profile and incidence of cardiovascular events: a population-based survey

    Directory of Open Access Journals (Sweden)

    Bullano Michael F

    2009-09-01

    Full Text Available Abstract Background Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. Methods Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization. Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. Results Of 17,640 respondents, 488 (2.8% reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2 [all p Conclusion Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

  7. The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis

    DEFF Research Database (Denmark)

    Hovland, Anders; Jonasson, Lena; Garred, Peter;

    2015-01-01

    Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role...... of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans...... to reduce atherosclerosis....

  8. Why did ancient people have atherosclerosis?: from autopsies to computed tomography to potential causes.

    Science.gov (United States)

    Thomas, Gregory S; Wann, L Samuel; Allam, Adel H; Thompson, Randall C; Michalik, David E; Sutherland, M Linda; Sutherland, James D; Lombardi, Guido P; Watson, Lucia; Cox, Samantha L; Valladolid, Clide M; Abd El-Maksoud, Gomaa; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; el-Halim Nur el-Din, Abd; Clarke, Emily M; Thomas, Ian G; Miyamoto, Michael I; Kaplan, Hillard S; Frohlich, Bruno; Narula, Jagat; Stewart, Alexandre F R; Zink, Albert; Finch, Caleb E

    2014-06-01

    Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors. PMID:25667093

  9. The association between periodontal disease parameters and severity of atherosclerosis

    Science.gov (United States)

    Ketabi, Mohammad; Meybodi, Fatemeh Rashidi; Asgari, Mohammad Reza

    2016-01-01

    Background: Atherosclerosis is the most common cause for heart attack and stroke. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. The aim of this research was to determine the possible association between chronic periodontal disease and severity of atherosclerosis. Materials and Methods: Eighty-two subjects that were referred to Chamran Heart Hospital in Isfahan for angiography were involved in this study. Fifty-nine subjects had coronary artery obstruction (CAO) and 23 showed no obstruction after angiography. The severity of CAO was assessed. Periodontal parameters including pocket depth (PD), gingival recession (R), clinical attachment level (CAL), and bleeding on probing (BOP) of all subjects were recorded. The decayed-missing-filled (DMF) index of all subjects was also measured. For statistical analysis, Pearson correlation test, Chi-square, and independent t-test were used. Results: There were significant positive correlation between variables R, PD, CAL, decayed (D), missing (M), DMF, BOP, and degree of CAO. However, there were no significant differences between filling variable degree of CAO (left anterior descending, left circumflex, and right coronary artery). Independent t-test showed that the mean of variables R, PD, AL, D, M, and DMF in patients with obstructed arteries were significantly higher than subjects without CAO. But there were no significant differences between variable F in two groups. Conclusion: The results of this cross-section analytical study showed an association between periodontal disease and dental parameters with the severity of CAO measured by angiography. However, this association must not interpret as a cause and effect relationship. PMID:27274346

  10. Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

    Science.gov (United States)

    Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

    2013-11-01

    Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.

  11. STAT4 deficiency reduces the development of atherosclerosis in mice.

    Science.gov (United States)

    Taghavie-Moghadam, Parésa L; Gjurich, Breanne N; Jabeen, Rukhsana; Krishnamurthy, Purna; Kaplan, Mark H; Dobrian, Anca D; Nadler, Jerry L; Galkina, Elena V

    2015-11-01

    Atherosclerosis is a chronic inflammatory process that leads to plaque formation in large and medium sized vessels. T helper 1 (Th1) cells constitute the majority of plaque infiltrating pro-atherogenic T cells and are induced via IFNγ-dependent activation of T-box (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (STAT4). We thus aimed to define a role for STAT4 in atherosclerosis. STAT4-deficiency resulted in a ∼71% reduction (p atherosclerosis (∼31%, p < 0.01) in western diet fed Stat4(-/-)Apoe(-/-) mice. Surprisingly, reduced atherogenesis in Stat4(-/-)Apoe(-/-) mice was not due to attenuated IFNγ production in vivo by Th1 cells, suggesting an at least partially IFNγ-independent pro-atherogenic role of STAT4. STAT4 is expressed in T cells, but also detected in macrophages (MΦs). Stat4(-/-)Apoe(-/-)in vitro differentiated M1 or M2 MΦs had reduced cytokine production compare to Apoe(-/-) M1 and M2 MΦs that was accompanied by reduced induction of CD69, I-A(b), and CD86 in response to LPS stimulation. Stat4(-/-)Apoe(-/-) MΦs expressed attenuated levels of CCR2 and demonstrated reduced migration toward CCL2 in a transwell assay. Importantly, the percentage of aortic CD11b(+)F4/80(+)Ly6C(hi) MΦs was reduced in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice. Thus, this study identifies for the first time a pro-atherogenic role of STAT4 that is at least partially independent of Th1 cell-derived IFNγ, and primarily involving the modulation of MΦ responses.

  12. The pigeon (Columba livia) model of spontaneous atherosclerosis.

    Science.gov (United States)

    Anderson, J L; Smith, S C; Taylor, R L

    2014-11-01

    Multiple animal models have been employed to study human atherosclerosis, the principal cause of mortality in the United States. Each model has individual advantages related to specific pathologies. Initiation, the earliest disease phase, is best modeled by the White Carneau (WC-As) pigeon. Atherosclerosis develops spontaneously in the WC-As without either external manipulation or known risk factors. Furthermore, susceptibility is caused by a single gene defect inherited in an autosomal recessive manner. The Show Racer (SR-Ar) pigeon is resistant to atherosclerosis. Breed differences in the biochemistry and metabolism of celiac foci cells have been described. For example, WC-As have lower oxidative metabolism but higher amounts of chondroitin-6-sulfate and nonesterified fatty acids compared with SR-Ar. Gene expression in aortic smooth muscle cells was compared between breeds using representational difference analysis and microarray analysis. Energy metabolism and cellular phenotype were the chief gene expression differences. Glycolysis and synthetic cell types were related to the WC-As but oxidative metabolism and contractile cell types were related to the SR-Ar. Rosiglitazone, a PPARγ agonist, blocked RNA binding motif (RBMS1) expression in WC-As cells. The drug may act through the c-myc oncogene as RBMS1 is a c-myc target. Proteomic tests of aortic smooth muscle cells supported greater glycosylation in the WC-As and a transforming growth factor β effect in SR-Ar. Unoxidized fatty acids build up in WC-As cells because of their metabolic deficiency, ultimately preventing the contractile phenotype in these cells. The single gene responsible for the disease is likely regulatory in nature.

  13. Effect of tocotrienol on aortic atherosclerosis in diabetic mice

    International Nuclear Information System (INIS)

    Effect of tocotrienol on aortic atherosclerosis in diabetic mice To study the histomorphological effect of tocotrienol on aortic atherosclerosis in diabetic mice having high fat diet. Study Design: Lab based randomized controlled trial. Place and Duration of Study: Army Medical College, Rawalpindi and National Institute of Health, Islamabad from November 2009 to June 2010. Material and Methods: Forty five female BALB/c mice were randomly divided into three groups. The diabetic mice model was established by intraperitoneal injection of streptozotocin (STZ) 40 mg/kg body weight. Group A was given normal laboratory diet, group B high fat diet and group C was given tocotrienol along with high fat diet for 32 weeks. At the end of experiment the mice were sacrificed. The hearts of animals were dissected out and ascending aortae were taken out. The specimen was fixed in 10% formol calcium and processed for paraffin embedding. Five micrometer thick sections were made for haematoxylin and eosin, and Verhoeff's staining. After staining, histomorphologic changes in slides were noted. Results: In contrast to group A, atheroscelrosis developed in groups B and C. Statistically significant atherosclerotic changes were found in the aortae of diabetic mice in group B when compared to group A. On comparison of group A to C, atherosclerotic changes were statistically insignificant. However when group B was compared with group C, the aortic atherosclerotic changes decreased significantly in group C. Conclusion: In diabetics with high fat diet intake, there is an increase in development of atherosclerosis in aorta which can be reduced by tocotrienol. (author)

  14. The occurrence of dental caries is associated with atherosclerosis

    Directory of Open Access Journals (Sweden)

    Bernhard Glodny

    2013-07-01

    Full Text Available OBJECTIVE: Previous studies have suggested that marginal periodontitis is a risk factor for developing atherosclerosis. The objective of this study was to determine whether caries may also be associated with atherosclerosis. METHODS: The computed tomography data sets of 292 consecutive patients, 137 women and 155 men with a mean age of 54.1±17.3 years, were analyzed. Caries were quantified based on the number of decayed surfaces of all the teeth, and periodontitis was quantified on the basis of the horizontal bone loss in the jaw. The presence of chronic apical periodontitis (CAP was assessed, and the aortic atherosclerotic burden was quantified using a calcium scoring method. RESULTS: The patients with <1 caries surfaces/tooth had a lower atherosclerotic burden (0.13±0.61 mL than patients with ≥1 caries surfaces/tooth. The atherosclerotic burden was greater in patients with a higher number of lesions with pulpal involvement and more teeth with chronic apical periodontitis. In the logistical regression models, age (Wald 49.3, number of caries per tooth (Wald 26.4, periodontitis (Wald 8.6, and male gender (Wald 11 were found to be independent risk factors for atherosclerosis. In the linear regression analyses, age and the number of decayed surfaces per tooth were identified as influencing factors associated with a higher atherosclerotic burden, and the number of restorations per tooth was associated with a lower atherosclerotic burden. CONCLUSION: Dental caries, pulpal caries, and chronic apical periodontitis are associated positively, while restorations are associated inversely, with aortic atherosclerotic burden. Prospective studies are required to confirm these observations and answer the question of possible causality.

  15. Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

    International Nuclear Information System (INIS)

    Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: → Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. → Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs

  16. Premature atherosclerosis in patients with acquired immunodeficiency syndrome

    Institute of Scientific and Technical Information of China (English)

    ZENG Yong; YE Yi-cong; LUO Ling; QIU Zhi-feng; HAN Yang; LI Xiao-meng; FANG Quan; ZHANG Shu-yang; LI Tai-sheng

    2010-01-01

    Background Increased risk of atherosclerosis has been reported in patients with human immunodeficiency virus (HIV)infection since highly active antiretroviral therapy (HAART) has come into use. However, there is no clear evidence of premature atherosclerosis in Chinese HIV-infected patients. Our study was designed to determine the relationship between HIV infection and atherosclerosis in Chinese HIV-infected patients.Methods One hundred and forty-five patients were enrolled in this study. These included 82 HIV-infected patients (41HAART-treated and 41 antiretroviral therapy (ART) naive patients) and 43 HIV-negative control subjects. Data on traditional cardiovascular risk factors, HIV infection parameters, and treatment regimens were collected. Pulse wave velocity (PWV) was determined using a pulse pressure analyzer to evaluate the function of the arterial wall as an indicator of atherosclerotic vascular damage.Results A higher PWV ((1358.3±117.8) cm/s vs. (1270.2±189.2) cm/s, P=0.010) was found in ART na(i)ve HIV-infected patients compared with control subjects. However, HAART treated patients had lower PWV compared to ART na(i)ve patients ((1283.8±181.4) cm/s vs. (1358.0±117.8) cm/s, P=0.033). Multiple regression analysis revealed that age (B=5.218, 95% confidence interval (CI) 1.420-9.016, P=0.008), current smoking (B=-74.671, 95% CI -147.003 to -2.339, P=0.043) and HAART (92.7% patients on a protease inhibitor-free regimen) (B=-169.169, 95% CI-272.508 to -65.831, P=0.010) were associated with reduced PWV in HIV-infected patients.Conclusions Reduced PWV in HIV-infected Chinese patients indicates that they are more likely to develop arterial wall stiffness, possibly by atherosclerosis. A protease inhibitor-free regime may be protective for arterial wall of HIV infected patients.

  17. Aging and atherosclerosis in human and nonhuman primates

    OpenAIRE

    Cefalu, William T.; Wagner, Janice D.

    1997-01-01

    Atherosclerosis is a major age-related process and public health problem and its clinical manifestations (coronary heart disease [CHD] and cerebrovascular disease) continue to be responsible for approximately 50% of all deaths occurring annually. In addition, CHD is responsible for over 70 to 80% of deaths among men and women over 65 years old. As our population ages (35 million people over the age of 65 in the U.S. by the year 2030) and because of the increased morbidity and mortality associ...

  18. Mechanistic similarities between trauma, atherosclerosis, and other inflammatory processes.

    Science.gov (United States)

    Scalea, Joseph R; Bromberg, Jonathan; Bartlett, Stephen T; Scalea, Thomas M

    2015-12-01

    Most human diseases, including trauma, atherosclerosis, and malignancy, can be characterized by either an overexuberant inflammatory response or an inadequate immunologic response. As our understanding of the mechanisms underlying these inflammatory aberrations improves, so should our approach to the patient. The development of novel technologies capable of exploiting inflammatory mediators will undoubtedly play a role in future patient-directed therapies. Trauma surgeons are uniquely positioned to usher in a new era of patient diagnostics and patient-directed therapies based on an understanding of the immune system's response to stimuli. These improvements are likely to affect not only trauma care but all aspects of medicine. PMID:26304513

  19. Depressive and anxiety disorders and risk of subclinical atherosclerosis Findings from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Seldenrijk, Adrie; Vogelzangs, Nicole; van Hout, Hein P. J.; van Marwijk, Harm W. J.; Diamant, Michaela; Penninx, Brenda W. J. H.

    2010-01-01

    Objective: Current evidence regarding the association between psychopathology and subclinical atherosclerosis show inconsistent results. The present study examined whether subclinical atherosclerosis was more prevalent in a large cohort of persons with depressive or anxiety disorders as compared to

  20. Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Nahoko Tanaka

    2016-09-01

    Full Text Available Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5% had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

  1. The natural history of aortic atherosclerosis: A systematic histopathological evaluation of the peri-renal region

    NARCIS (Netherlands)

    R.A. van Dijk; R. Virmani; J.H. von der Thusen; A.F. Schaapherder; J.H.N. Lindeman

    2010-01-01

    Background: Risk factor profiles for the different vascular beds (i.e. coronary, carotid, peripheral and aortic) are remarkably different, suggesting that atherosclerosis is a heterogeneous disorder. Little is known about the morphologic progression of atherosclerosis in the peri-renal aorta, one of

  2. Experimental atherosclerosis in rabbits on diets with milk fat and different proteins

    NARCIS (Netherlands)

    Hermus, R.J.J.

    1975-01-01

    In this thesis the literature about the pathogenesis of atherosclerosis has been reviewed. The various risk indicators for atherosclerosis are discussed and related to the theory about atherogenesis. A review of the influence of milk fat constituents and dietary proteins on serum lipids and atherosc

  3. Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

    Science.gov (United States)

    Tanaka, Nahoko; Masuoka, Shotaro; Kusunoki, Natsuko; Nanki, Toshihiro; Kawai, Shinichi

    2016-09-16

    Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI) were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5%) had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT) increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI) at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

  4. Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice : An immunohistochemical study

    NARCIS (Netherlands)

    Gijbels, M.J.J.; Cammen, M. van der; Laan, L.J.W. van der; Emeis, J.J.; Havekes, L.M.; Hofker, M.H.; Kraal, G.

    1999-01-01

    Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study athero

  5. Extent of atherosclerosis and prognosis of patients with aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    van den Bergh, W M; Algra, A; Elias, R; Rinkel, G J E

    2006-01-01

    BACKGROUND AND PURPOSE: Atherosclerosis impairs the endothelial dependent vasodilatation and may change the diameter and plasticity of cerebral vessels. The aim of this study was to investigate if an index of the occurrence of atherosclerosis is associated with the risk of delayed cerebral ischemia

  6. Prevention of Coronary Atherosclerosis: The Role of a College Health Service.

    Science.gov (United States)

    Manchester, Ralph A.; Greenland, Philip

    1987-01-01

    This paper reviews the concept of behavioral risk factors for atherosclerosis which become entrenched in adolescence or young adulthood. Evidence favoring intervention in the adolescent years and a screening program at the University of Rochester Health Service are described. A preliminary strategy for prevention of atherosclerosis on campus is…

  7. Fibrinogen and P-selectin expression in atherosclerosis model of Sprague Dawley rat

    Institute of Scientific and Technical Information of China (English)

    ZHOU Bi-rong; PAN Ying; ZHAI Zhi-min

    2011-01-01

    Background Platelet P-selectin plays an important role in inflammation and contributes to thrombosis and hemostasis.Fibrinogen may take part in inflammation,thrombosis,and hemostasis via enhancement of platelet P-selectin expression.This study aimed to discover the correlation between them in atherosclerosis model of Sprague Dawley (SD) rat.Methods Diet-induced atherosclerosis SD rats were adopted as experimental models.The blood from the common abdominal aorta of the rats was obtained to measure the biochemical characteristics and for the check of flow cytometry.Then the aortas were separated carefully,taken out,put into 10% (w/v) neutral formalin for later use.Then fibrinogen and P-selectin expression were detected by flow cytometry and immunohistochemistry.Results SD rats were induced to atherosclerosis model by high fat diet and vitamin D2 injected.It was discovered that the binding of fibrinogen and the expression of P-selectin on the platelet increase in atherosclerosis model (Group H)than in that in the control group (Group Z),there were closely interrelated.High levels of fibrinogen and P-selectin express on the artery of atherosclerosis rat model.Conclusions Fibrinogen and P-selectin are concerned with atherosclerosis.Fibrinogen can interact with P-selectin in order to contribute to the development of atherosclerosis,high levels of fibrinogen and P-selectin can be regarded as risk factors for markers of atherosclerosis.

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

    OpenAIRE

    Xiaojuan Ma; Yingmei Feng

    2016-01-01

    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 r...

  9. Signs of subclinical coronary atherosclerosis in relation to risk factor distribution in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR)

    OpenAIRE

    Erbel, Raimund; Delaney, Joseph A. C.; Lehmann, Nils; McClelland, Robyn L.; Möhlenkamp, Stefan; Kronmal, Richard A.; Schmermund, Axel; Moebus, Susanne; Dragano, Nico; Stang, Andreas; Jöckel, Karl-Heinz; Budoff, Matthew J.

    2008-01-01

    Aims Modern imaging technology allows us the visualization of coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis. The prevalence, quantity, and risk factors for CAC were compared between two studies with similar imaging protocols but different source populations: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR). Methods and results The measured CAC in 2220 MESA participants were compared with those in 3126 HNR partici...

  10. Telomere Length and the Cancer–Atherosclerosis Trade-Off

    Science.gov (United States)

    Stone, Rivka C.; Horvath, Kent; Kark, Jeremy D.; Susser, Ezra; Tishkoff, Sarah A.; Aviv, Abraham

    2016-01-01

    Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan. PMID:27386863

  11. Putative targeting of matrix metalloproteinase-8 in atherosclerosis.

    Science.gov (United States)

    Ye, Shu

    2015-03-01

    There is compelling evidence indicating that some members of the matrix metalloproteinase (MMP) family play important roles in the pathogenesis of atherosclerosis and related vascular and cardiac conditions such as atherosclerotic plaque rupture leading to myocardial infarction, heart failure after myocardial infarction, neointima formation following angioplasty, and abdominal aortic aneurysm. Studies have shown that administration of MMP inhibitors can deter some of these conditions in experimental animal models, but few pertinent human clinical trials have been reported to date. Clinical studies of broad-spectrum MMP inhibitors in cancers and arthritis, however, have reported considerable side effects that are likely to be related to the lack of selectivity of these inhibitors. Since different members of the MMP family can have divergent and even opposing functions, it is believed that selective MMP inhibitors that specifically target particular MMPs that are key in the disease pathogenesis will likely have greater efficacy and less adverse effects. In recent years there has been accumulating evidence indicating an important role of MMP8 in atherosclerosis and the associated conditions mentioned above. This article will review findings from studies examining MMP8 in relation to these conditions and discuss rationale of targeting MMP8 as a potential therapeutic strategy.

  12. Dialysis modalities as risk factors in the development of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Damjanović Tatjana

    2003-01-01

    Full Text Available Introduction Atherosclerosis is a major risk factor for increased cardiovascular morbidity and mortality in dialysis patients. First clinical symptoms are usually associated with initial atherosclerotic changes of blood vessels. The aim of this study was ultrasound evaluation of intimae media thickness (IMT of carotid arteries in dialysis patients and its correlation with certain risk factors. Patients and methods IMT was measured in 45 dialysis patients with no signs of cardiovascular diseases:15 continuous ambulatory peritoneal dialysis (CAPD patients, 30 haemodialysis (HD patients and in 20 healthy controls. IMT was correlated with certain risk factors for atherosclerosis (general parameters - age, gender, duration of dialysis cause of renal diseases, parameters of nutrition, parameters of calcium and phosphorus metabolism, lipid parameters, blood pressure and smoking. Results The mean carotid artery IMT was significantly higher in dialysis patients than in the control group (p<0.05. In addition, the mean IMT was statistically significantly higher in PD than in HD patients (p<0.05. In CAPD patients there was a significant correlation between IMT and total and LDL cholesterol. In the second group (HD patients IMT was significantly correlated with diastolic blood pressure, BMI and smoking. Conclusion Although atherosclerotic cardiovascular disease may not manifest in dialysis patients, IMT of carotid arteries significantly increases. Major risk factors affecting IMT are lipid disturbances in patients on peritoneal dialysis and hypertension, obesity and smoking in HD patients.

  13. Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

    Directory of Open Access Journals (Sweden)

    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.

  14. Update on medical management of dyslipidemia and atherosclerosis.

    Science.gov (United States)

    Ginter, E; Simko, V

    2013-01-01

    Scientific achievements revealing the pathogenesis of atherosclerosis resulted in the second half of the 20th century in major improvement in prevention and therapy of cardiovascular disorders (CVD). Essential became the understanding of a critical pathogenetic role of the low-density lipoproteins (LDL), mainly their oxidized form (oxLDL) and also the protective potential of the high-density lipoproteins (HDL). CVD is now regarded to be an inflammatory disease in which a systemic inflammatory reaction is combined with an accumulation of immune cells in atherosclerotic plaques. Higher intake of antioxidants in fruit and vegetable, life style modifications, cessation of smoking, physical exercise and introduction of medications that lower LDL and promote HDL (statins, niacin and fibrates) resulted in a substantial decline of the killer effect of unmanaged CVD. In the United Kingdom the male CVD mortality declined between 1970 and 2009 from 700 to 200 deaths per 100,000. In France, CVD mortality in the middle age population (25-64 years) is now responsible for death in only 15 % men and in 11 % women. Unfortunately, in many parts of the world CVD mortality remains a prominent population scourge. Recent discoveries, especially on the role of peroxisome proliferator-activated receptors (PPAR) and antisense compounds used in addition to established anti-atherogenic medications, promise further gains in the fight against atherosclerosis (Fig. 4, Ref. 54).

  15. Telomere Length and the Cancer-Atherosclerosis Trade-Off.

    Science.gov (United States)

    Stone, Rivka C; Horvath, Kent; Kark, Jeremy D; Susser, Ezra; Tishkoff, Sarah A; Aviv, Abraham

    2016-07-01

    Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan. PMID:27386863

  16. Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

    Science.gov (United States)

    Mulvihill, Erin E; Burke, Amy C; Huff, Murray W

    2016-07-17

    Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents. PMID:27146015

  17. Wine, alcohol and atherosclerosis: clinical evidences and mechanisms

    Directory of Open Access Journals (Sweden)

    P.L. da Luz

    2004-09-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease which may cause obstructions of the coronary, cerebral and peripheral arteries. It is typically multifactorial, most often dependent on risk factors such as hypercholesterolemia, diabetes, smoking, hypertension, sedentarism, and obesity. It is the single main cause of death in most developed countries due to myocardial infarction, angina, sudden death, and heart failure. Several epidemiological studies suggest that moderate alcohol intake, especially red wine, decrease cardiac mortality due to atherosclerosis. The alcohol effect is described by a J curve, suggesting that moderate drinkers may benefit while abstainers and heavy drinkers are at higher risk. Experimental studies indicate that most beneficial effects of drinking are attributable to flavonoids that are present in red wine, purple grape juice and several fruits and vegetables. The mechanisms include antiplatelet actions, increases in high-density lipoprotein, antioxidation, reduced endothelin-1 production, and increased endothelial nitric oxide synthase expression which causes augmented nitric oxide production by endothelial cells. These findings lead to the concept that moderate red wine drinking, in the absence of contraindications, may be beneficial to patients who are at risk of atherosclerotic cardiovascular events. Moreover, a diet based on fruits and vegetables containing flavonoids may be even more beneficial.

  18. Imaging of coronary atherosclerosis - evolution towards new treatment strategies.

    Science.gov (United States)

    Dweck, Marc R; Doris, Mhairi K; Motwani, Manish; Adamson, Philip D; Slomka, Piotr; Dey, Damini; Fayad, Zahi A; Newby, David E; Berman, Daniel

    2016-09-01

    Coronary atherosclerosis and the precipitation of acute myocardial infarction are highly complex processes, which makes accurate risk prediction challenging. Rapid developments in invasive and noninvasive imaging technologies now provide us with detailed, exquisite images of the coronary vasculature that allow direct investigation of a wide range of these processes. These modalities include sophisticated assessments of luminal stenoses and myocardial perfusion, complemented by novel measures of the atherosclerotic plaque burden, adverse plaque characteristics, and disease activity. Together, they can provide comprehensive, individualized assessments of coronary atherosclerosis as it occurs in patients. Not only can this information provide important pathological insights, but it can also potentially be used to guide personalized treatment decisions. In this Review, we describe the latest advances in both established and emerging imaging techniques, focusing on the strengths and weakness of each approach. Moreover, we discuss how these technological advances might be translated from attractive images into novel imaging strategies and definite improvements in clinical risk prediction and patient outcomes. This process will not be easy, and the many potential barriers and difficulties are also reviewed. PMID:27226154

  19. Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.

    Science.gov (United States)

    Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin; Tellides, George; Simons, Michael

    2016-01-01

    The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFβ signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFβ signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFβ activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2α led to a profound inhibition of atherosclerotic plaque growth when these animals were crossed on Apoe(-/-) background and subjected to a high-fat diet. In particular, there was a significant reduction in plaque cellularity, increase in fibrous cap area, and decrease in necrotic core size. In agreement with these findings, examination of human coronary arteries with various degrees of atherosclerosis revealed a strong correlation between the activation of FGF signaling, loss of TGFβ activity, and increased disease severity. These results identify SMC FGF/TGFβ signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth. PMID:27189169

  20. Imaging of coronary atherosclerosis in various susceptible groups.

    Science.gov (United States)

    Munnur, Ravi Kiran; Nerlekar, Nitesh; Wong, Dennis T L

    2016-08-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Atherosclerosis, which is the primary pathophysiologic mechanism for the development of plaque leading to CAD, is a multifactorial process resulting from a complex interplay between genetic susceptibility and various risk factors such as hypertension (HT), dyslipidaemia, diabetes mellitus (DM) and smoking. In addition, influences from other disease states such as chronic kidney disease (CKD), obesity and the metabolic syndrome as well as gender and ethnic diversity also contribute to the disease process. Insights from pathological observations and advances in cellular and molecular biology have helped us understand the process of plaque formation, progression and rupture leading to events. Several intravascular imaging techniques such as intravascular ultrasound (IVUS), Virtual histology IVUS (VH-IVUS) and optical coherence tomography (OCT) allow in vivo assessment of plaque burden, plaque morphology and response to therapy. In addition, non invasive assessment using coronary artery calcium (CAC) score allows risk stratification and plaque burden assessment whilst computed tomography coronary angiography (CTCA) allows evaluation of luminal stenosis, plaque characterisation and quantification. This review aims to summarise the results of invasive and non-invasive imaging studies of coronary atherosclerosis seen in various high-risk populations including DM, metabolic syndrome, obesity, CKD and, gender differences and ethnicity. Understanding the phenotype of plaques in various susceptible groups may allow potential development of personalised therapies. PMID:27500095

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

    Science.gov (United States)

    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. PMID:25174928

  2. Periodontitis-atherosclerosis syndrome: an expanded model of pathogenesis.

    Science.gov (United States)

    Offenbacher, S; Madianos, P N; Champagne, C M; Southerland, J H; Paquette, D W; Williams, R C; Slade, G; Beck, J D

    1999-10-01

    The early reports of a linkage between periodontitis and atherosclerosis have garnered further support by additional data generated by several investigative teams in many different countries. The evidence continues to suggest that periodontitis may be an important risk factor or risk indicator for cardiovascular pathology for some individuals. The term periodontitis-atherosclerosis syndrome (PAS) is proposed as a new diagnostic term to describe this condition in these individuals. Current evidence, albeit preliminary in nature, which describes a cluster of clinical signs and symptoms that are associated with this condition, is presented. It is clear that this syndrome will require considerable study and refinement before a definitive diagnosis and treatment plan can be formulated. Potential mechanisms by which systemic inflammation and infectious challenge of periodontal origin may serve as a potential modifier of cardiovascular disease are discussed in the context of a detailed working model of pathogenesis. This hypothetical model embraces many cellular and molecular components of atherogenesis and thromboembolic diseases from the perspective of periodontitis pathogenesis. Many aspects of the hypothetical model remain unproved; however, it is our opinion that only through the clarification of the mechanisms of pathogenesis can we ultimately construct a knowledge framework for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on the cardiovascular system represents an unprecedented challenge to our profession. PMID:10685359

  3. Coronary, Carotid, and Lower-extremity Atherosclerosis and Their Interrelationship in Danish Patients with Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Kay, Susan Due; Poulsen, Mikael Kjaer; Diederichsen, Axel Cosmus Pyndt;

    2015-01-01

    OBJECTIVE: Atherosclerosis is highly prevalent among patients with systemic lupus erythematosus (SLE), but has been demonstrated predominantly in non-European SLE cohorts and few investigations have included more than 1 imaging modality. We aimed to investigate the prevalence of atherosclerosis...... regression model, age (p Systemic Lupus International Collaborating Clinics (SLICC; p = 0.008) were significant independent risk factors for atherosclerosis at any vascular territory. CONCLUSION: Atherosclerosis is highly prevalent among Danish patients with SLE...

  4. 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

    BACKGROUND: Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. METHODS AND RESULTS: The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean...... 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...... or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2-3 sites), or generalized (4-6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63...

  5. 75 FR 63488 - Submission for OMB Review; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...

    Science.gov (United States)

    2010-10-15

    ... Study of Atherosclerosis (MESA) Event Surveillance SUMMARY: Under the provisions of Section 3507(a)(1)(D... Collection: Title: Multi-Ethnic Study of Atherosclerosis (MESA) Event Surveillance. Type of Information... disease (CVD)-- that is, atherosclerosis and other forms of CVD that have not produced signs and...

  6. The coexistence of carotid and lower extremity atherosclerosis further increases cardio-cerebrovascular risk in type 2 diabetes

    OpenAIRE

    Li, Mei-Fang; Zhao, Cui-Chun; Li, Ting-ting; Tu, Yin-Fang; Lu, Jun-Xi; Zhang, Rong; Chen, Ming-Yun; Bao, Yu-Qian; Li, Lian-Xi; Jia, Wei-Ping

    2016-01-01

    Background Both carotid and lower limb atherosclerosis are associated with increased cardiovascular and cerebrovascular risks. However, it is still unclear whether the concomitant presence of carotid and lower extremity atherosclerosis further increases the cardiovascular and cerebrovascular risks. Therefore, our aim is to investigate whether the coexistence of carotid and lower extremity atherosclerosis was associated with higher cardiovascular and cerebrovascular risks in patients with type...

  7. Atherosclerosis in coronary artery and aorta in a semi-urban population by applying modified American Heart Association classification of atherosclerosis: An autopsy study

    Science.gov (United States)

    Thej, Mothakapalli Jagadish; Kalyani, Raju; Kiran, Jayaramaiah

    2012-01-01

    Background: Ischemic heart disease (IHD) following atherosclerosis is a giant killer and the incidence of atherosclerosis in coronary arteries is rapidly increasing among Indians. The study was formulated to assess the histomorphological atherosclerotic changes in aorta and coronary arteries at autopsy by applying the modified American Heart Association classification of atherosclerosis based on morphological descriptions to find out the age and sex related prevalence of atherosclerosis in the semi-urban population of Kolar, a district in Southern India. Materials and Methods: Autopsy was conducted on 113 cases whose age ranged from 8-85 years. Autopsy was conducted by the conventional technique; heart and the aorta were removed and fixed in 10% formalin. The heart was dissected along the direction of flow of blood and aorta along the posterior surface. Microscopic assessment of the three main coronary arteries and aorta was done using the modified American Heart Association classification of atherosclerosis. Proportions were analyzed using Chi-square test. Results: The number of males was 78 (69%) and number of females was 35 (31%). Mean age was 37.11 ± 15.69 years. Increased incidence of intermediate lesions was noted in young individuals (15-34 yrs). Atherosclerotic lesions were more in left anterior descending artery compared to other coronary arteries and in abdominal aorta compared to thoracic and ascending aorta. Vulnerable plaques were more in right coronary artery. Conclusion: With cardiovascular disease attaining pandemic proportions, the study of subclinical atherosclerosis is the need of the hour to estimate the disease burden in the asymptomatic population. The increased amount of atherosclerosis (advanced and intermediate lesions) found in the young population in this study gives an indication that anti-atherogenic preventive measures need to be implemented in young individuals, so as to prevent coronary artery disease from causing premature death

  8. AIP1-mediated stress signaling in atherosclerosis and arteriosclerosis.

    Science.gov (United States)

    Zhang, Jiqin; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

    2015-05-01

    AIP1 (ASK1-interacting protein-1; encoded by the DAB2IP gene), a signaling scaffolding protein, is abundantly expressed in vascular endothelial cells (EC). While it was initially discovered as an apoptosis signal-regulating kinase 1 (ASK1)-interacting protein, AIP1 broadly suppresses inflammatory responses triggered by cytokines and stresses such as TNF, LPS, VEGF, and endoplasmic reticulum (ER) stress in EC (therefore, AIP1 is an anti-inflammatory protein). Human genome-wide association study (GWAS) has identified DAB2IP gene variants conferring susceptibility to cardiovascular diseases. Consistently, a global or vascular EC-specific deletion of DAB2IP in mice strongly enhances inflammatory responses and exacerbates atherosclerosis and graft arteriosclerosis progression in mouse models. Mechanisms for AIP1 function and regulation associated with human cardiovascular diseases need further investigations.

  9. Dynamic Aspects of Macrophage Polarizationduring Atherosclerosis Progression and Regression

    Directory of Open Access Journals (Sweden)

    Michael ePeled

    2014-11-01

    Full Text Available It is well recognized that macrophages in many contexts in vitro and in vivo display a spectrum of inflammatory features and functional properties. A convenient system to group together different subsets of macrophages has been the M1(inflammatory/M2(anti-inflammatory classification. In addition to other sites of inflammation, it is now established that atherosclerotic plaques contain both M1 and M2 macrophages. We review results made possible by a number of recent mouse models of atherosclerotic regression that, taken with other literature, have shown the M1/M2 balance in plaques to be dynamic, with M1 predominating in disease progression and M2 in regression. The regulation of the macrophage phenotype in plaques and the functional consequences of the M1 and M2 states in atherosclerosis will also be discussed.

  10. Cathepsins and cystatin C in atherosclerosis and obesity.

    Science.gov (United States)

    Lafarge, Jean-Charles; Naour, Nadia; Clément, Karine; Guerre-Millo, Michèle

    2010-11-01

    Given the increasing prevalence of human obesity worldwide, there is an urgent need for a better understanding of the molecular mechanisms linking obesity to metabolic and cardiovascular diseases. Our knowledge is nevertheless limited regarding molecules linking adipose tissue to downstream complications. The importance of cathepsins was brought to light in this context. Through a large scale transcriptomic analysis, our group recently identified the gene encoding cathepsin S as one of the most deregulated gene in the adipose tissue of obese subjects and positively correlated with body mass index. Other members of the cathepsin family are expressed in the adipose tissue, including cathepsin K and cathepsin L. Given their implication in atherogenesis, these proteases could participate into the well established deleterious relationship between enlarged adipose tissue and increased cardiovascular risk. Here, we review the clinical and experimental evidence relevant to the role of cathepsins K, L and S and their most abundant endogenous inhibitor, cystatin C, in atherosclerosis and in obesity.

  11. Human neutrophil elastase: mediator and therapeutic target in atherosclerosis.

    Science.gov (United States)

    Henriksen, Peter A; Sallenave, Jean-Michel

    2008-01-01

    Human neutrophil elastase (HNE) is present within atherosclerotic plaques where it contributes to matrix degradation and weakening of the vessel wall associated with the complications of aneurysm formation and plaque rupture. It is joined by other extracellular proteases in these actions but the broad range of substrates and potency of HNE coupled with the potential for rapid increases in HNE activity associated with neutrophil degranulation in acute coronary syndromes single this disruptive protease out as therapeutic target in atherosclerotic disease. This review summarises the role of HNE in neutrophil-mediated endothelial injury and the evidence for HNE as a mediator of atherosclerotic plaque development. The therapeutic potential of HNE neutralising antiproteases, alpha-1-antitrypsin and elafin, in atherosclerosis, is discussed. PMID:18289916

  12. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

    Directory of Open Access Journals (Sweden)

    López, Sergio

    2009-03-01

    Full Text Available Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing “omics” techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall.La aterosclerosis es una enfermedad en la que múltiples factores, entre los que se encuentra la dieta, contribuyen a la degradación de la pared vascular. En la etiología de la aterogénesis son determinantes las lipoproteínas plasmáticas y los distintos tipos celulares de la pared vascular, incluyendo una respuesta inflamatoria. La ingesta de alimentos afecta la concentración y composición de las lipoproteínas, ejerciendo un papel de riesgo o protector durante las diferentes etapas del proceso aterosclerótico. Es importante destacar que la naturaleza de las lipoproteínas y por lo tanto su papel en la enfermedad cardiovascular, también depende del tiempo transcurrido entre comidas. Por ejemplo, las lipoprote

  13. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  14. Subclinical heart failure in juvenile idiopathic arthritis: a consequence of chronic inflammation and subclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Hamada S Ahmad

    2016-01-01

    Conclusion Our findings indicate the presence of subclinical heart failure in these patients. JIA patients with subclinical atherosclerosis, with systemic disease, and with active disease are at greatest risk of developing subclinical heart failure.

  15. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  16. Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study

    NARCIS (Netherlands)

    R. van Leeuwen (Redmer); M.K. Ikram (Kamran); J.R. Vingerling (Hans); J.C.M. Witteman (Jacqueline); P.T.V.M. de Jong (Paulus); A. Hofman (Albert)

    2003-01-01

    textabstractPURPOSE: To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS: The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlan

  17. Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Damir Hamamdzic

    2013-01-01

    Full Text Available Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9 gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

  18. Testing the Role of Myeloid Cell Glucose Flux in Inflammation and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Tomohiro Nishizawa

    2014-04-01

    Full Text Available Inflammatory activation of myeloid cells is accompanied by increased glycolysis, which is required for the surge in cytokine production. Although in vitro studies suggest that increased macrophage glucose metabolism is sufficient for cytokine induction, the proinflammatory effects of increased myeloid cell glucose flux in vivo and the impact on atherosclerosis, a major complication of diabetes, are unknown. We therefore tested the hypothesis that increased glucose uptake in myeloid cells stimulates cytokine production and atherosclerosis. Overexpression of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and flux through the pentose phosphate pathway but did not induce cytokines. Moreover, myeloid-cell-specific overexpression of GLUT1 in LDL receptor-deficient mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux is insufficient for inflammatory myeloid cell activation and atherogenesis. If glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid cells do not appear to be the key targets.

  19. Induction of atherosclerosis in mice and hamsters without germline genetic engineering

    DEFF Research Database (Denmark)

    Bjørklund, Martin Mæng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup;

    2014-01-01

    RATIONALE: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. OBJECTI...

  20. A diet rich in green and yellow vegetables inhibits atherosclerosis in mice.

    Science.gov (United States)

    Adams, Michael R; Golden, Deborah L; Chen, Haiying; Register, Thomas C; Gugger, Eric T

    2006-07-01

    Although dietary patterns characterized by a high intake of fruits and vegetables are associated with reduced risk of coronary heart disease, the mechanisms involved are uncertain. We determined the effects of a diet rich in green and yellow vegetables on the development of atherosclerosis, the underlying cause of coronary heart disease, in a mouse model of atherosclerosis, the LDL receptor -/-, apolipoprotein B transgenic mouse. The mice were randomized into 2 diet groups: 1) a vegetable-free control diet (n = 53) and 2) the same diet with 30% (w:w) replaced by an equal-parts mixture of freeze-dried peas, green beans, broccoli, corn, and carrots (n = 54). Mice were fed these diets for 16 wk. Aortic atherosclerosis, as estimated by cholesteryl ester content, was reduced 38% (P yellow vegetables inhibits the development of atherosclerosis and may therefore lead to a reduction in the risk of coronary heart disease. PMID:16772454

  1. Contrasting effect of fish oil supplementation on the development of atherosclerosis in murine models

    DEFF Research Database (Denmark)

    Zampolli, Antonella; Bysted, Anette; Leth, Torben;

    2006-01-01

    Objective: Increased fish oil intake is associated with protection against coronary heart disease and sudden death, while effects on atherosclerosis are controversial. We explored the effects of supplementing fish oil (rich in n-3 polyunsaturated fatty acids, PUFA) or corn oil (rich in n-6 PUFA......) in two different models of atherosclerosis. Methods and Results: Sixty-three low density lipoprotein receptor-deficient (LDLR-/-) mice and sixty-nine apolipoprotein E-deficient (apoE(-/-)) mice were fed diets without supplementations or supplemented with either 1% fish oil or 1% corn oil. In apo......E(-/-) mice, neither fish oil nor corn oil had any major impact on plasma lipids or atherosclerosis. In LDLR-/- mice, conversely, the fish oil and the corn oil group had lower levels of LDL-cholesterol and triglycerides and had lesser atherosclerosis in the aortic root and in the entire aorta (P

  2. Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

    DEFF Research Database (Denmark)

    Bagger, Y Z; Rasmussen, Henrik Berg; Alexandersen, P;

    2007-01-01

    Epidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids...

  3. Transendothelial exchange of low-density lipoprotein is unaffected by the presence of severe atherosclerosis

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Jensen, Trine Krogsgaard;

    2004-01-01

    OBJECTIVE: We tested the hypothesis that transendothelial exchange of low-density lipoprotein (LDL) is influenced by the presence of severe atherosclerosis; we previously found this exchange elevated in diabetes patients. METHODS: By an in vivo isotope method, we compared transendothelial LDL...... exchange in 24 patients with angiographically verified coronary atherosclerosis, 11 patients with angiographically verified peripheral atherosclerosis, 60 patients with diabetes, and in 42 controls. Autologous 131-iodinated LDL ((131)I-LDL) and 125-iodinated albumin ((125)I-albumin) were injected...... intravenously (i.v.), and the 1-h fractional escape rates (FER(LDL) and FER(alb)) were taken as indices of transendothelial exchange. RESULTS: Patients with coronary or peripheral atherosclerosis had FER(LDL) similar to that of controls [4.3 (3.5-5.1) and 3.2 (2.3-4.1) versus 4.2 (3.7-4.7)%/h; P>0.05], even...

  4. 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...

  5. Inflammatory therapeutic targets in coronary atherosclerosis – from molecular biology to clinical application

    Directory of Open Access Journals (Sweden)

    Fabian eLinden

    2014-11-01

    Full Text Available Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over three years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecu-lar inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

  6. The role of peptide hormones (adiponectin, leptin, insulin in the pathogenesis of atherosclerosis

    Directory of Open Access Journals (Sweden)

    S. A. Smetnev

    2015-11-01

    Full Text Available Currently, cardiovascular diseases (CVD remain the main problem in the world and in Russia in particular. The study of the causes and progression of atherosclerosis is a critical moment in the fight against CVD. Adipose tissue and processes that occur in it attracts attention in recent years. The important role of adipose tissue as an endocrine and immune organ is revealed as well as its participation in the development of the inflammatory process. This leads to the development of initial manifestations of atherosclerosis a precursor of many metabolic disorders and CVD. Particular attention causes adipokines regulatory peptide hormones in the adipose tissue, as well as insulin, due to its close relationship with the adipose tissue and especially with adiponectin and leptin. Recent data on the role of adiponectin, leptin and insulin in the pathogenesis of atherosclerosis in order to identify new potential targets among peptide hormones for the treatment of atherosclerosis are presented. 

  7. Prevention of atherosclerosis in patients living with HIV

    Directory of Open Access Journals (Sweden)

    Ferruccio De Lorenzo

    2009-03-01

    Full Text Available Ferruccio De Lorenzo1, Marta Boffito1, Sophie Collot-Teixeira2, Brian Gazzard1, John L McGregor2,3, Kevin Shotliff2, Han Xiao41General Medicine and Prevention of Vascular Disorders, Beta Cell Diabetes Centre and St Stephen’s AIDS Trust, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 2Kings College London, Cardiovascular Division, London, UK; 3INSERM U970, PARC Hôpital Européen George Pompidou, Paris, France; 4Cardiology Department, Homerton University Hospital NHS, London, UKInvestigational product: Rosuvastatin (Crestor®; Astra Zeneca.Active ingredients: Rosuvastatin (5 mg.Study title: Prevention of Atherosclerosis in Patients Living with HIV.Phase of study: Phase III.Aims: Primary aim:• To assess whether rosuvastatin therapy could slow the progression of the carotid intima-media thickness (C-IMT; as measured by the change in the mean IMT of the near and far walls of the distal common carotid arteries over 2 years in HIV-infected patients (HIV-IP.Secondary aims:• To assess whether rosuvastatin therapy could reduce highly sensitive C reactive protein (hs-CRP inflammatory marker that is increased in HIV-IP.• To assess the effect of rosuvastatin therapy on serum lipid levels (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG] and apolipoproteins (APO A1, APO B and APO B/A1.• To assess the safety of rosuvastatin in HIV-IP through the evaluation of clinical laboratory analyses (liver function tests and creatine kinase and adverse events (AEs.Study design: Two-year randomized, double-blind, placebo-controlled, parallel group study.Planned sample size: 320 HIV-IP.Summary of eligibility criteria: HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm3. Patients must be stable on combination antiretroviral therapy (cART for at least 12 months and have a 10-year CVD risk of less than 20% (using the

  8. Spontaneous Atherosclerosis in Free-Living Pigeons in Mosul Area, Iraq

    OpenAIRE

    Hahfidh I. Al-Sadi* and Ashraf K. Abdullah

    2011-01-01

    The purpose of this study was to investigate for the first time the prevalence and pathology of spontaneous atherosclerosis in free – living pigeons in Mosul, Iraq. A hundred apparently healthy, 1-1.5 year old both sex pigeons of local breed free – living used. Effects of factors such as weight, sex, age and health status on prevalence of the condition were also studied. Prevalence of naturally occurring atherosclerosis was 10%. Grossly, the heart was hypertrophied and of firm consistency, ao...

  9. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    OpenAIRE

    Dolores Busso; Lilian Mascareño; Francisca Salas; Loni Berkowitz; Nicolás Santander; Alonso Quiroz; Ludwig Amigo; Gloria Valdés; Attilio Rigotti

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed a...

  10. NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice

    OpenAIRE

    Langbein, Heike; Brunssen, Coy; Hofmann, Anja; Cimalla, Peter; Brux, Melanie; Bornstein, Stefan R; Deussen, Andreas; Koch, Edmund; Morawietz, Henning

    2015-01-01

    Aims Endothelial dysfunction is an early step in the development of atherosclerosis. Increased formation of superoxide anions by NADPH oxidase Nox1, 2, and 5 reduces nitric oxide availability and can promote endothelial dysfunction. In contrast, recent evidence supports a vasoprotective role of H2O2 produced by main endothelial isoform Nox4. Therefore, we analysed the impact of genetic deletion of Nox4 on endothelial dysfunction and atherosclerosis in the low-density lipoprotein receptor (Ldl...

  11. Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice

    OpenAIRE

    Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

    2012-01-01

    Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control i...

  12. Lower Zinc Bioavailability May Be Related to Higher Risk of Subclinical Atherosclerosis in Korean Adults

    OpenAIRE

    Su Kyoung Jung; Mi-Kyung Kim; Young-Hoon Lee; Dong Hoon Shin; Min-Ho Shin; Byung-Yeol Chun; Bo Youl Choi

    2013-01-01

    BACKGROUND: There is a proposed link between dietary zinc intake and atherosclerosis, but this relationship remains unclear. Phytate may contribute to this relationship by influencing zinc bioavailability. OBJECTIVE: The aim of this study is to examine the relationship between zinc bioavailability and subclinical atherosclerosis in healthy Korean adults. MATERIALS AND METHODS: The present cross-sectional analysis used baseline data from the Korean multi-Rural Communities Cohort Study (MRCohor...

  13. Wall thickness of the carotid artey as an indicator of generalized atherosclerosis : the Rotterdam study

    OpenAIRE

    Bots, Michiel

    1993-01-01

    textabstractThe past decades have led to a better understanding of the etiology and pathogenesis of atherosclerosis and its clinical sequelae. Several risk factors have been identified that promote atherosclerosis to develop and of which it is currently known that their presence increases the risk of cardiovascular disease. At present, cardiovascular disease is believed to be caused by an interplay of advanced atherosclerotic vessel wall changes, stenosis and thrombosis. However, the question...

  14. Serum Carotenoids Reduce Progression of Early Atherosclerosis in the Carotid Artery Wall among Eastern Finnish Men

    OpenAIRE

    Jouni Karppi; Sudhir Kurl; Kimmo Ronkainen; Jussi Kauhanen; Laukkanen, Jari A.

    2013-01-01

    BACKGROUND: Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids. METHODS: We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between conce...

  15. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation

    OpenAIRE

    Cuff, Carolyn A.; Kothapalli, Devashish; Azonobi, Ijeoma; Chun, Sam; Zhang, Yuanming; Belkin, Richard; Yeh, Christine; Secreto, Anthony; Richard K Assoian; Rader, Daniel J; Puré, Ellen

    2001-01-01

    Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD4...

  16. Molecular mechanisms of atherosclerosis in metabolic syndrome: role of reduced IRS2-dependent signaling

    OpenAIRE

    González-Navarro, Herminia; Vinué, Ángela; Vila-Caballer, Marian; Fortuño, Ana; Beloqui, Oscar; Zalba, Guillermo; Burks, Deborah J.; Díez, Javier; Andrés, Vicente

    2008-01-01

    OBJECTIVE: The mechanisms underlying accelerated atherosclerosis in metabolic syndrome (MetS) patients remain poorly defined. In the mouse, complete disruption of insulin receptor substrate-2 (Irs2) causes insulin resistance, MetS-like manifestations, and accelerates atherosclerosis. Here, we performed human, mouse, and cell culture studies to gain insight into the contribution of defective Irs2 signaling to MetS-associated alterations. METHODS AND RESULTS: In circulating leukocytes from ...

  17. Atherosclerosis of the descending aorta predicts cardiovascular events: a transesophageal echocardiography study

    Directory of Open Access Journals (Sweden)

    Havasi Kálmán

    2004-10-01

    Full Text Available Abstract Purpose Previous studies have shown that atherosclerosis of the descending aorta detected by transesophageal echocardiography (TEE is a good marker of coexisting coronary artery disease. The aim of our study was to evaluate whether the presence of atherosclerosis on the descending aorta during TEE has any prognostic impact in predicting cardiovascular events. Material and Methods The study group consisted of 238 consecutive in-hospital patients referred for TEE testing (135 males, 103 females, mean age 58 +/- 11 years with a follow up of 24 months. The atherosclerotic lesions of the descending aorta were scored from 0 (no atherosclerosis to 3 (plaque >5 mm and/or "complex" plaque with ulcerated or mobile parts. Results Atherosclerosis was observed in 102 patients, (grade 3 in 16, and grade 2 in 86 patients whereas 136 patients only had an intimal thickening or normal intimal surface. There were 57 cardiovascular events in the follow-up period. The number of events was higher in the 102 patients with (n = 34 than in the 136 patients without atherosclerosis (n = 23, p =2 (HR 2.4, CI 1.0–5.5 predicted hard cardiovascular events. Conclusion Atherosclerosis of the descending aorta observed during transesophageal echocardiography is a useful predictor of cardiovascular events.

  18. Preclinical mouse models and methods for the discovery of the causes and treatments of atherosclerosis

    Science.gov (United States)

    Hewing, Bernd; Fisher, Edward A

    2013-01-01

    Introduction Atherosclerosis is the leading cause of death in the Western world. Despite huge advances in understanding its pathophysiological mechanisms, current treatment is mostly based on ‘traditional’ risk factors. The introduction of statins more than 20 years ago reduced morbidity and mortality of atherosclerosis by 30%, leaving a residual cardiovascular risk. Therefore, efforts continue toward the development of novel therapies that can be added to established treatments. Besides targeting dyslipidemia, recent focus has been put on preventing or resolving inflammatory processes involved in atherosclerosis. Areas covered The article discusses therapeutic and diagnostic targets in atherosclerosis and how they can be discovered and studied in preclinical animal models. The roles of immune cells, specifically macrophages and monocytes, in plaque inflammation are discussed. The article also describes current preclinical models of atherosclerosis, specifically the mouse, study designs (for progression and regression studies), basic and advanced methods of analysis of atherosclerotic lesions, and discusses the challenges of translating the findings to humans. Expert opinion Advances in genomics, proteomics, lipidomics and the development of high-throughput screening techniques help to improve our understanding of atherosclerosis disease mechanisms immensely and facilitate the discovery of new diagnostic and therapeutic targets. Preclinical studies in animals are still indispensable to uncover pathways involved in atherosclerotic disease and to evaluate novel drug targets. The translation of these targets, however, from animal studies to humans remains challenging. There is a strong need for novel biomarkers that can be used to prove the concept of a new target in humans. PMID:22468952

  19. TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis

    Science.gov (United States)

    Mahmoud, Marwa M.; Kim, Hyejeong Rosemary; Xing, Rouyu; Hsiao, Sarah; Mammoto, Akiko; Chen, Jing; Serbanovic-Canic, Jovana; Feng, Shuang; Bowden, Neil P.; Maguire, Richard; Ariaans, Markus; Francis, Sheila E.; Weinberg, Peter D.; van der Heiden, Kim; Jones, Elizabeth A.; Chico, Timothy J.A.; Ridger, Victoria

    2016-01-01

    Rationale: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown. Objective: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease. Methods and Results: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness. Conclusions: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development. PMID:27245171

  20. Omics-based approaches to understand mechanosensitive endothelial biology and atherosclerosis.

    Science.gov (United States)

    Simmons, Rachel D; Kumar, Sandeep; Thabet, Salim Raid; Sur, Sanjoli; Jo, Hanjoong

    2016-09-01

    Atherosclerosis is a multifactorial disease that preferentially occurs in arterial regions exposed to d-flow can be used to indicate disturbed flow or disturbed blood flow. The mechanisms by which d-flow induces atherosclerosis involve changes in the transcriptome, methylome, proteome, and metabolome of multiple vascular cells, especially endothelial cells. Initially, we begin with the pathogenesis of atherosclerosis and the changes that occur at multiple levels owing to d-flow, especially in the endothelium. Also, there are a variety of strategies used for the global profiling of the genome, transcriptome, miRNA-ome, DNA methylome, and metabolome that are important to define the biological and pathophysiological mechanisms of endothelial dysfunction and atherosclerosis. Finally, systems biology can be used to integrate these 'omics' datasets, especially those that derive data based on a single animal model, in order to better understand the pathophysiology of atherosclerosis development in a holistic manner and how this integrative approach could be used to identify novel molecular diagnostics and therapeutic targets to prevent or treat atherosclerosis. WIREs Syst Biol Med 2016, 8:378-401. doi: 10.1002/wsbm.1344 For further resources related to this article, please visit the WIREs website. PMID:27341633

  1. ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association

    Directory of Open Access Journals (Sweden)

    Graziano Riccioni

    2014-04-01

    Full Text Available Asymmetric dimethylarginine (ADMA is an endogenous nitric oxide synthase (NOS inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT and plaque in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI. All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque (p < 0.001, with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p < 0.001. High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects.

  2. Asymptomatic Atherosclerosis in Egyptian Rheumatoid Arthritis Patients and Its Relation to Disease Activity

    Directory of Open Access Journals (Sweden)

    Rawhya R. Elshereef

    2015-01-01

    Full Text Available Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1 and 40 healthy controls (group 11. All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls P=0.003**. A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease P=0.0001*** and patient’s age P=0.01*. There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients.

  3. The Potential Effect of Puerarin in Preventing Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    朱庆磊; 何爱霞; 韩慧蓉; 吕欣然; 王士雯

    2002-01-01

    Objective:To study the activity of Puerarin (Pue) in scavenging oxygen free radical(OFR) and its inhibitory effect on the oxidative modification of low density lipoprotein (LDL). Methods:Riboflavin-light system was used to generate superoxide anion, and Fenton reaction to generate hydroxylfree radical to study the activity of Pue in scavenging OFR. Hydrogen peroxide-induced hemolysis wasused to study the effect of Pue on erythrocyte hemolysis and malondialdehyde (MDA) production. And ul-traviolet ray and cupric sulfate were used to cause the oxidative modification of LDL for studying the inhib-itory effect of Pue on LDL oxidative modification. Results: (1) Pue could, at concentration of 0.01-1.0mmol/L, scavenge superoxide anion radical and at concentration of 7.5-75μmol/L scavenge hydroxyl rad-ical in a concentration dependent manner. (2) Pue could, at concentration of 0.1-10 mmol/L, inhibit sig-nificantly oxidative hemolysis and MDA production of erythrocyte induced by hydrogen peroxide. (3) Pueof 0.01-1.0 mmol/L could inhibit the oxidative modification of LDL in a concentration dependent man-ner. Conclusion: Pue has an anti-peroxidation effect and shows a potential effect in preventing atherosclero-sis.

  4. Nitric oxide-oxygen radicals interactions in atherosclerosis.

    Science.gov (United States)

    Rubbo, H; Batthyany, C; Radi, R

    2000-01-01

    Atherosclerosis is one of the most common diseases and the principal cause of death in western civilization. The pathogenesis of this disease can be explained on the basis of the 'oxidative-modification hypothesis,' which proposes that low-density lipoprotein (LDL) oxidation represents a key early event. Nitric oxide (*NO) regulates critical lipid membrane and lipoprotein oxidation events by a) contributing to the formation of more potent secondary oxidants from superoxide (i.e.: peroxynitrite), and b) its antioxidant properties through termination reactions with lipid radicals to possibly less reactive secondary nitrogen-containing products (LONO, LOONO). Relative rates of production and steady state concentrations of superoxide and *NO and cellular sites of production will profoundly influence the expression of differential oxidant injury-enhancing and protective effects of *NO. Full understanding of the physiological roles of *NO, coupled with detailed insight into *NO regulation of oxygen radical-dependent reactions, will yield a more rational basis for intervention strategies directed toward oxidant-dependent atherogenic processes. PMID:15693284

  5. Multifocal atherosclerosis in patient after acute first degree radiation sickness.

    Directory of Open Access Journals (Sweden)

    Metlyaeva N.A.

    2014-12-01

    Full Text Available Purpose: assessment the heavy psychosomatic and all-somatic cardiovascular and cerebrovascular pathology of patient, transferred an acute I degree radiation sickness, from the general evenly gamma-beta radiation. Conclusions. The subdepressive and disturbing-depressive syndrome of patient, transferred an acute radiation sickness (ARS of I degree, from the general evenly gamma-beta radiation, was independent risk factor of development of multifocal atherosclerosis; Features of development of all-somatic and psychosomatic pathology of patient are based on a combination of genetic prerequisites, environment influences (the stress caused by accident on the ChNPP and social factors, influencing on him during a course of life, especially during early socialization. Thus at development of psychosomatic frustration the combination of feature of the mental reaction connected with the personal characteristic and special relationship between mental (stress and physiological (somatic by aspects of reaction which led to metabolism violation, to aging, decrease in adaptation opportunities of an organism and development age — dependent pathology took place.

  6. The simulation of magnetic resonance elastography through atherosclerosis.

    Science.gov (United States)

    Thomas-Seale, L E J; Hollis, L; Klatt, D; Sack, I; Roberts, N; Pankaj, P; Hoskins, P R

    2016-06-14

    The clinical diagnosis of atherosclerosis via the measurement of stenosis size is widely acknowledged as an imperfect criterion. The vulnerability of an atherosclerotic plaque to rupture is associated with its mechanical properties. The potential to image these mechanical properties using magnetic resonance elastography (MRE) was investigated through synthetic datasets. An image of the steady state wave propagation, equivalent to the first harmonic, can be extracted directly from finite element analysis. Inversion of this displacement data yields a map of the shear modulus, known as an elastogram. The variation of plaque composition, stenosis size, Gaussian noise, filter thresholds and excitation frequency were explored. A decreasing mean shear modulus with an increasing lipid composition was identified through all stenosis sizes. However the inversion algorithm showed sensitivity to parameter variation leading to artefacts which disrupted both the elastograms and quantitative trends. As noise was increased up to a realistic level, the contrast was maintained between the fully fibrous and lipid plaques but lost between the interim compositions. Although incorporating a Butterworth filter improved the performance of the algorithm, restrictive filter thresholds resulted in a reduction of the sensitivity of the algorithm to composition and noise variation. Increasing the excitation frequency improved the techniques ability to image the magnitude of the shear modulus and identify a contrast between compositions. In conclusion, whilst the technique has the potential to image the shear modulus of atherosclerotic plaques, future research will require the integration of a heterogeneous inversion algorithm. PMID:27130475

  7. Increased prostacyclin and thromboxane A2 biosynthesis in atherosclerosis

    International Nuclear Information System (INIS)

    It has been proposed that atherosclerotic arteries produce less prostacyclin (PGI2) than nonatherosclerotic arteries do, thereby predisposing arteries to vasospasm and thrombosis in vivo. The authors reexamined this concept by measuring spontaneous as well as arachidonate-induced PGI2 biosynthesis in aortic segments from nonatherosclerotic and cholesterol-fed atherosclerotic New Zealand White rabbits. Thromboxane A2 (TXA2) generation was also measured. Formation of PGI2, as well as TXA2, as measured by radioimmunoassay (RIA) of their metabolites, was increased in atherosclerotic aortic segments relative to nonatherosclerotic segments at 0, 5, 10, 15 and 30 min of incubation with arachidonate. Pretreatment of arterial segments with indomethacin inhibited PGI2 as well as TXA2 formation, whereas pretreatment with the selective TXA2 inhibitor OKY-046 inhibited only TXA2 release, thus confirming the identity of icosanoids. To confirm the RIA data, aortic segments were incubated with [14C]arachidonate prior to stimulation with unlabeled arachidonate. The uptake of arachidonate was similar, but the release of incorporated [14C]arachidonate was significantly greater in atherosclerotic segments than in nonatherosclertic ones. Thus, synthesis of PGI2 as well as TXA2 is increased in atherosclerosis, and this alteration in arachidonate metabolism is related to increased release of arachidonate

  8. [Glycation of extracellular matrix proteins and its role in atherosclerosis].

    Science.gov (United States)

    Kuzan, Aleksandra; Chwiłkowska, Agnieszka; Kobielarz, Magdalena; Pezowicz, Celina; Gamian, Andrzej

    2012-10-29

    Glycation consists in formation of advanced glycation end-products (AGE) during non-enzymatic reaction between reducing sugars and proteins, lipids or nucleic acids. This review is focused mainly on glycation of collagen and its role in acceleration of vascular disease. Collagen is an extracellular matrix protein characterized by unique structure forming fibrils with great anti-tensile and anti-breaking strength. The protein builds the connective tissue and is responsible for biomechanical properties of blood vessels. It is reported that higher content of glycated collagen correlates with lower elasticity and greater toughness of the vessel walls and, as a consequence, a faster rate of atherosclerosis development. Numerous mechanisms connected with AGE formation are involved in atherogenesis, among others: receptor-mediated production of free radicals, triggering an inflammatory process, activation of leukocytes and thrombocytes, facilitation of LDL binding, change in level of growth factors, adhesion molecules, MMP and some other proteins' expression. The coverages allow the development of therapeutic strategies to prevent or slow down the pathological processes connected with glycation of collagen and other proteins in the artery wall. The main strategies are based on limitation of exogenous AGE, consumption of products which contain rutin, treatment with drugs which inhibit AGE formation, such as pyridoxamine, and chemicals which are able to cleave already formed AGE protein-protein crosslinks, such as ALT-711.

  9. Contrast-enhanced ultrasound for imaging vasa vasorum: Comparison with histopathology in a swine model of atherosclerosis

    OpenAIRE

    Schinkel, Arend; Krueger, Chris; Tellez, Armando; Granada, Juan; Reed, Jess; Hall, Anne; Zang, William; Owens, Cindy; Kaluza, Grzegorz; Staub, Daniel; Coll, Blai; Cate, Folkert; Feinstein, Steven

    2010-01-01

    textabstractAimTo evaluate the agreement between contrast-enhanced ultrasound imaging and histopathology in an animal model of atherosclerosis.Methods and results: Atherosclerosis was studied in both femoral arteries of four Rapacz familial hypercholesterolaemia (RFH) swine. Contrast-enhanced ultrasound imaging of the eight femoral arteries was performed at baseline and at 5, 12, 26, and 43 weeks follow-up after percutaneous transluminal stimulation of atherosclerosis to assess the progressio...

  10. MicroRNA-155 in the pathogenesis of atherosclerosis: a conflicting role?

    Science.gov (United States)

    Ma, Xiaochun; Ma, Chi; Zheng, Xia

    2013-10-01

    Atherosclerosis is widely appreciated to involve a chronic lipid-induced inflammatory reaction of the arterial wall in response to haemodynamic stress and dyslipidaemia. The dysfunction of resident vascular cells and recruitment of infiltrating leukocyte cells orchestrate a complex interplay in the initiation and development of atherosclerosis. Despite a great many advances in recent years, the detailed mechanisms modulating the inflammation in atherosclerosis have not been fully elucidated. MicroRNAs (miRNAs) are small non-coding RNA (ncRNA) molecules that regulate gene expression post-transcriptionally by degradation and translational repression of target messenger RNAs (mRNAs). Substantial evidence demonstrates that miRNAs play a vital role in the physiological control of gene expression and in the pathogenesis of malignant, infectious, and cardiovascular disorders. MiR-155, a typical multi-functional miRNA, has recently emerged as a novel component of inflammatory signal transduction in the pathogenesis of atherosclerosis. MiR-155-mediated regulation is extensively involved in endothelial cells (ECs), macrophages, dendritic cell (DCs), vascular smooth muscle cells (VSMCs) and differentiation of leukocyte subsets. MiR-155 can modulate the expression of genes correlated with inflammation in different cell types in vitro and also affect the atherogenesis in vivo. However, miR-155 appears to play a conflicting role in the disease pathogenesis. Besides, miR-155 is potentially applied as a novel disease biomarker and therapeutic target in diagnosing and treating atherosclerosis. This article reviews the pertinent literature and mechanisms of action of miR-155 that have thus far been associated with atherosclerosis. Here we first introduce in brief the basic knowledge of the miRNA regulation and later discuss with emphasis the regulatory role of miR-155 in various cell types involved in atherosclerosis. PMID:23827206

  11. 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

  12. Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.

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    Yafeng Li

    Full Text Available Urotensin II (UII is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013. Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005, 11% in the thoracic aorta (P = 0.054 and 18% in the abdominal aorta (P = 0.035. These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.

  13. 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.

  14. Differentially expressed microRNAs at different stages of atherosclerosis in ApoE-deficient mice

    Institute of Scientific and Technical Information of China (English)

    SHAN Zhen; YAO Chen; LI Zi-lun; TENG Yuan; LI Wen; WANG Jin-song; YE Cai-sheng

    2013-01-01

    Background Atherosclerosis is the primary cause of cardiovascular disease,carotid artery disease,and peripheral vascular disease.However,it is hard to obtain human arterial tissue at different stages of atherosclerosis for a systematic study.The ApoE-deficient (ApoE 1-) mice predictably develop spontaneous atherosclerotic plaques with numerous features similar to the human lesions and contain nearly the entire spectrum of lesions observed during atherogenesis in humans.MicroRNA expression profiles at different stages of atherosclerosis in ApoE-deficient mice were screened to find out the differentially expressed microRNAs.Methods ApoE-deficient mice were euthanized at 4,8,and 20 weeks of age and divided into three groups according to the three time points,including groups A4 (fed a Western-type diet for 0 week),A8 (fed a Western-type diet for 4 weeks),and A20 (fed a Western-type diet for 16 weeks).Atherosclerotic lesions were analyzed.Fifteen aortas were collected and combined into three pools (five aortas in one pool) in each group.MicroRNA microarray analysis was replicated thrice in each group.The threshold of fold change ≥2.0 was used to screen up or down-regulated microRNAs.Differentially expressed microRNAs were subsequently verified with quantitative real-time polymerase chain reaction.Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis were selected.Results Atherosclerotic lesions first appeared in the aortic arch in group A8.Severe atherosclerotic lesions were observed in group A20.In group A8,seven MicroRNAs were up-regulated while two were down-regulated.In group A20,15 microRNAs were up-regulated while two were down-regulated.miR-34a-Sp and miR-497-5p were increasingly up-regulated,while miR-434-3p was progressively down-regulated when atherosclerosis progressed.Conclusions In this study,we described that microRNAs are differentially expressed at different stages of atherosclerosis in ApoE-deficient mice

  15. Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish.

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    Sang Joon Lee

    Full Text Available Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis.

  16. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

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    Dolores Busso

    2014-01-01

    Full Text Available The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5, E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%. In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice.

    Science.gov (United States)

    Steffens, Sabine; Veillard, Niels R; Arnaud, Claire; Pelli, Graziano; Burger, Fabienne; Staub, Christian; Karsak, Meliha; Zimmer, Andreas; Frossard, Jean-Louis; Mach, François

    2005-04-01

    Atherosclerosis is a chronic inflammatory disease, and is the primary cause of heart disease and stroke in Western countries. Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions and therefore have potential for the treatment of inflammatory diseases. We investigated the effects of THC in a murine model of established atherosclerosis. Oral administration of THC (1 mg kg(-1) per day) resulted in significant inhibition of disease progression. This effective dose is lower than the dose usually associated with psychotropic effects of THC. Furthermore, we detected the CB2 receptor (the main cannabinoid receptor expressed on immune cells) in both human and mouse atherosclerotic plaques. Lymphoid cells isolated from THC-treated mice showed diminished proliferation capacity and decreased interferon-gamma secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis, was also inhibited in vitro by THC. All these effects were completely blocked by a specific CB2 receptor antagonist. Our data demonstrate that oral treatment with a low dose of THC inhibits atherosclerosis progression in the apolipoprotein E knockout mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, THC or cannabinoids with activity at the CB2 receptor may be valuable targets for treating atherosclerosis.

  19. Anti-Inflammatory Effects of Vinpocetine in Atherosclerosis and Ischemic Stroke: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Linjie Zhang

    2014-12-01

    Full Text Available Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines—this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor κ-light-chain-enhancer of activated B cells κB (NF-κB pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-κB pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke.

  20. Obesity, hypertension and hypercholesterolemia as risk factors for atherosclerosis leading to ischemic events.

    Science.gov (United States)

    van Rooy, Mia-Jeanne; Pretorius, E

    2014-01-01

    Atherosclerosis is a widespread disease of the arterial system that is generated by injury to the vasculature due to hypercholesterolemia, hypertension and inflammatory diseases. In the current review, we discuss the role of different risk factors, including obesity, hypertension and hypercholesterolemia in atherosclerosis, which may ultimately lead to either cardiovascular or cerebral complication. Inflammation plays a pivotal role in conjunction with obesity, hypertension and hypercholesterolemia in the etiology of atherosclerosis. We discuss the role of inflammation with regards to reactive oxygen species (ROS) linked to the specific risk factors. The role of nitric oxide (NO) in conjunction with ROS is also important. Correlations of inflammatory cytokines and their functions in the mentioned risk factors are also discussed. The risk factors may ultimately lead to ischemic events, including transient ischemic attacks (TIAs), thrombotic stroke and myocardial infarction. Importantly, it seems as if there is a combination of pathophysiological triggers that may eventually result in atherosclerosis. Therefore, atherosclerosis is not the result of only one risk factor, but a combination of various physiological processes such as homeostasis and the inflammatory response. Ultimately, each patient's risk profile is unique and determines their immediate risk for acute thrombotic events or lethal ischemia.

  1. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

    Science.gov (United States)

    Slocum, C; Kramer, C; Genco, C A

    2016-07-01

    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease. PMID:26791914

  2. Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development

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    Luciana R. Fernandes

    2013-01-01

    Full Text Available Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages.

  3. Analysis on Homocysteine's Risk to Atherosclerosis and Its Correlations with Serum Lipids

    Institute of Scientific and Technical Information of China (English)

    李河; 郭兰; 肖敏; 陈铁峰; 吴书林; 余细勇; 石美铃; 董太明; 刘小清; 黄平; 李义和

    2004-01-01

    Objectives To explore the homocysteine's risk to atherosclerosis and its correlations with serum lipids TG,TG and HDL-C. Methods With a cross sectional study, 490 subjects (aged 41-86 yrs, male 420 and female 70) were surveyed in 1999 in Guangdong Province, China. The main research variables were homocysteine (Hcy) and the serum lipids total cholesterol (TC), triglyceride (TG),high-density lipoprotein cholesterol(HDL-C). Results Hcy was a possible risk factor resulting in atherosclerosis (OR=l.15, 0.05 <P <0.10, n=108) with Logistic regression analysis. There is no correlation or much lower degree correlation between Hey and the serum lipids group of TC, TG, HDL-C. The canonical correlation coefficient between V1 and W1 was R1,Can =0.12(0.05<P<0.10, n=490, V1=Hcy, W1= - 0.9446 * TC + 0.1588 * TG + 0.6009 * HDL-C). Conclusions It is possible that Hcy is a risk factor to atherosclerosis and is independent of serum lipids group or has much lower correlation with it. It is necessary to do more research to explore the risk degree of Hcy inducing atherosclerosis and whether are there are bigger correlations or higher independence between Hcy and other risk factors during the progress of atherosclerosis.

  4. Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.

    Science.gov (United States)

    Potekhina, Alexandra V; Pylaeva, Ekaterina; Provatorov, Sergey; Ruleva, Natalya; Masenko, Valery; Noeva, Elena; Krasnikova, Tatiana; Arefieva, Tatiana

    2015-01-01

    Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively. We aimed to investigate the balance of circulating Treg and Th17 in stable angina patients with different stages of coronary atherosclerosis. Methods. Treg, Th17 and Th1 cell frequencies were studied in 117 patients via direct immunofluorescence staining and flow cytometry. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone previous coronary stenting; in Group 2 no coronary atherosclerosis progression was found, in Group 3 patients had disease progression in non-invaded coronary arteries. Group 4 had severe coronary atherosclerosis. Results. The frequencies of CD4+CD25highCD127low, CD4+foxp3+, and CD4+IL10 + T cells were decreased, and CD4+IL17 + T cells frequencies were increased in group 4 vs. 1. Treg/Th17 ratios were declined in groups 3 and 4 vs. groups 1 and 2. IL-10 level was lower while hsCRP and sCD25 levels were higher in group 4 vs. 1. Conclusion. We assume that the imbalance in pro- and anti-inflammatory/atherogenic lymphocyte subpopulations is associated with atherosclerosis progression.

  5. Increased plasma levels of Lp(a) enhance the development of coronary atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    LI Ying; XU Hong; ZHOU Qin; WANG Chang-yuan; LIU Yan-xia; LU Yuan-yuan; FAN Jiang-lin; SUN Hui-jun

    2008-01-01

    Objective To test the hypothesis that increased plasma levels of Lp(a) may enhance the development of atherosclerosis in the setting of hypercholesterolemia. Methods The plasma Lp(a) was analyzed by SDS-PAGE Western blotting and quantitated using specific ELISA kits. Plasma total cholesterol, triglycerides and HDL-cholesterol were determined using Wako assay kits. The left coronary artery was used for the evaluation of coronary atherosclerosis (stenosis %). For quantitative study of the lesions in coronary atherosclerosis, hematoxylin- eosin and Elastica - van Gieson staining were used. To study cellular components ( SMC vs. macrophages) and Lp(a) deposits in the lesions, immunohistochemical staining was performed and then image analysis system was used. Results Plasma total cholesterol, triglycerides, or HDL-C were not significantly different between transgenic (Trg) and nontransgenic (nonTrg) rabbits. Trg rabbits had 200 % increase in coronary stenosis caused by atherosclerosis. The lesions of Trg WHHL rabbits contained more SMCs and less macrophage than those of nonTrg WHHL rabbits. Conclusions The results suggest that increased plasma levels of Lp(a) enhance the development of coronary atherosclerosis.

  6. Correlation between Serum Level of Adiponectin and Severity of Coronary Artery Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Lei Juan; Zhou Shuxian; Xue Shengneng; Zhang Yuling; Fang Chang; Luo Niansang

    2007-01-01

    Objectives To investigate the correlation between serum level of adiponectin and severity of coronary artery atherosclerosis. Methods Coronary angiographies were performed and serum levels of adiponectin were measured in 88 patients with suspected coronary heart disease (CHD). Patients were divided into groups according to the coronary angiographies and Gensini's scores of coronary artery atherosclerosis. The serum levels of adiponectin were compared in different groups, and multiple regressions were used to analyze the correlation factors of adiponectin. Results ①Serum adiponectin concentration in CHD group [ 7.1 mg/L(2.4 ~21.1 mg/L) ] was decreased as compared with that in control group [ 11.6 mg/L(4.4 ~ 28.2 mg/L),P<0.01 ]; ②The serum levels of adiponectin fell while the Gensini' s scores of coronary artery atherosclerosis increased ( P<0.05, P<0.01 ); ③Serum level of adiponectin was positively correlated with the high-density lipoprotein cholesterol, while negatively correlated with the Gensini' s score of coronary artery atherosclerosis and triglyceride (P<0.01 ). Conclusions Serum adiponectin concentration was decreased in patients with CHD.Low serum levels of adiponectin reflected the severity of coronary artery atherosclerosis. Adiponectin was a protective factor of cardiovascular system.

  7. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

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    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (PConclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  8. Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population.

    Science.gov (United States)

    Kutikhin, Anton G; Ponasenko, Anastasia V; Khutornaya, Maria V; Yuzhalin, Arseniy E; Zhidkova, Irina I; Salakhov, Ramil R; Golovkin, Alexey S; Barbarash, Olga L; Barbarash, Leonid S

    2016-09-01

    Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011-2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID:27200266

  9. 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.

  10. (Second) Harmonic Disharmony: Nonlinear Microscopy Shines New Light on the Pathology of Atherosclerosis.

    Science.gov (United States)

    Watson, Shana R; Lessner, Susan M

    2016-06-01

    There has been increasing interest in second harmonic generation (SHG) imaging approaches for the investigation of atherosclerosis due to the deep penetration and three-dimensional sectioning capabilities of the nonlinear optical microscope. Atherosclerosis involves remodeling or alteration of the collagenous framework in affected vessels. The disease is often characterized by excessive collagen deposition and altered collagen organization. SHG has the capability to accurately characterize collagen structure, which is an essential component in understanding atherosclerotic lesion development and progression. As a structure-based imaging modality, SHG is most impactful in atherosclerosis evaluation in conjunction with other, chemically specific nonlinear optics (NLO) techniques to identify additional components of the lesion. These include the use of coherent anti-Stokes Raman scattering and two-photon excitation fluorescence for studying atherosclerosis burden, and application of stimulated Raman scattering to image cholesterol crystals. However, very few NLO studies have attempted to quantitate differences in control versus atherosclerotic states or to correlate the application to clinical situations. This review highlights the potential of SHG imaging to directly and indirectly describe atherosclerosis as a pathological condition. PMID:27329310

  11. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation

    Science.gov (United States)

    Cuff, Carolyn A.; Kothapalli, Devashish; Azonobi, Ijeoma; Chun, Sam; Zhang, Yuanming; Belkin, Richard; Yeh, Christine; Secreto, Anthony; Assoian, Richard K.; Rader, Daniel J.; Puré, Ellen

    2001-01-01

    Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50–70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the “synthetic” state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms. PMID:11581304

  12. CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis

    Science.gov (United States)

    Silva, Rosemeire A.; Giordano, Ricardo J.; Gutierrez, Paulo S.; Rocha, Viviane Z.; Rudnicki, Martina; Kee, Patrick; Abdalla, Dulcinéia S. P.; Puech-Leão, Pedro; Caramelli, Bruno; Arap, Wadih; Pasqualini, Renata; Meneghetti, José C.; Marques, Fabio L. N.; Khoobchandani, Menka; Katti, Kattesh V.; Lugão, Ademar B.; Kalil, Jorge

    2016-01-01

    The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p 95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases. PMID:27563889

  13. Serum uric acid is a risk factor for large-artery atherosclerosis cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Jianjun Guo; Qingyu Shen; Jie Li; Xiaoming Rong; Ying Peng; Yamei Tang

    2011-01-01

    Using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery occlusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.

  14. Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer;

    2008-01-01

    Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

  15. Imaging Atherosclerosis with Hybrid Positron Emission Tomography/Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Kjær, Andreas

    2015-01-01

    Noninvasive imaging of atherosclerosis could potentially move patient management towards individualized triage, treatment, and followup. The newly introduced combined positron emission tomography (PET) and magnetic resonance imaging (MRI) system could emerge as a key player in this context. Both...... PET and MRI have previously been used for imaging plaque morphology and function: however, the combination of the two methods may offer new synergistic opportunities. Here, we will give a short summary of current relevant clinical applications of PET and MRI in the setting of atherosclerosis....... Additionally, our initial experiences with simultaneous PET/MRI for atherosclerosis imaging are presented. Finally, future potential vascular applications exploiting the unique combination of PET and MRI will be discussed....

  16. Inhibitory effect of the paraoxonase gene on the formation of rabbit coronary atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Jing Bai; Hui Zhou; Xin-Hong Yang; Hua-Fen Liu; Yan-Yan Meng

    2013-01-01

    Objective: To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene (PON-1) which transfected to the rabbit epicardial adipose tissue. Methods:Rabbit coronary atherosclerosis model was established by high-fat feeding, liposome-encapsulated recombinant plasmid pEGFP-PON-1 50 μL was injected to the rabbit pericardial cavity, and was harvested 4 weeks after transfection. Results: The epicardial fat transfected PON-1 gene had effect on the high lipid level. It significantly increased expression of PON-1 in peripheral arterial vascular tissue (P<0.05); and significantly reduced total cholesterol and low-density lipoprotein cholesterol levels (P<0.05), and the thickness ratio of coronary artery intima/media (P <0.05). Conclusions: The injection of the PON-1 gene in the pericardial cavity can effectively suppress the formation of coronary atherosclerosis.

  17. 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 CXCL4...... and by enhanced monocyte arrest resulting from CCL5-CXCL4 interactions. The CCL5 antagonist Met-RANTES reduces diet-induced atherosclerosis; however, CCL5 antagonism may not be therapeutically feasible, as suggested by studies using Ccl5-deficient mice which imply that direct CCL5 blockade would severely...... 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...

  18. Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits.

    Science.gov (United States)

    Xu, Jingshu; Jüllig, Mia; Middleditch, Martin J; Cooper, Garth J S

    2015-09-01

    The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans.

  19. Future non-invasive imaging to detect vascular plaque instability and subclinical non-obstructive atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Arnon Blum; Menachem Nahir

    2013-01-01

    Atherosclerosis underlies the major causes of death in the Western World. Our main goal is to detect early changes of atherosclerosis and to identify subjects at highest cardiovascular risk that may aid in the development of prevention approaches and better management that will decrease cardiovascular morbidity and mortality. The new methods that are of interest include the advanced vascular ultrasound methods, the infra red and near infra red imaging techniques, the EndoPat device that reflects peripheral arterial tone, the electron beam computed tomography, the magnetic resonance imaging, and the molecular imaging techniques. In this review we will focus on the future of advanced imaging techniques that are being developed to detect early (pre-clinical) development of atherosclerosis.

  20. Recent Advances in Targeted, Self-Assembling Nanoparticles to Address Vascular Damage Due to Atherosclerosis.

    Science.gov (United States)

    Chung, Eun Ji; Tirrell, Matthew

    2015-11-18

    Self-assembling nanoparticles functionalized with targeting moieties have significant potential for atherosclerosis nanomedicine. While self-assembly allows the easy construction (and degradation) of nanoparticles with therapeutic or diagnostic functionality, or both, the targeting agent can direct them to a specific molecular marker within a given stage of the disease. Therefore, supramolecular nanoparticles have been investigated in the last decade as molecular imaging agents or explored as nanocarriers that can decrease the systemic toxicity of drugs by producing accumulation predominantly in specific tissues of interest. In this Progress Report, the pathogenesis of atherosclerosis and the damage caused to vascular tissue are described, as well as the current diagnostic and treatment options. An overview of targeted strategies using self-assembling nanoparticles is provided, including liposomes, high density lipoproteins, protein cages, micelles, proticles, and perfluorocarbon nanoparticles. Finally, an overview is given of current challenges, limitations, and future applications for personalized medicine in the context of atherosclerosis of self-assembling nanoparticles.

  1. Development of Integrated Multimodality Intravascular Imaging System for Assessing and Characterizing Atherosclerosis

    Science.gov (United States)

    Chen, Zhongping

    Atherosclerosis is one of the major causes of morbidity and mortality in developed countries. Early detection of plaque lesions is the first and most necessary step towards preventing the lethal consequences of atherosclerosis. Currently, many biomedical imaging techniques aimed at imaging and assessing vulnerable plaques have been reported in literature. Unfortunately, atherosclerosis is often asymptomatic, as vulnerable plaques grow without causing any detrimental side effects until rupturing. Due to this complication, the information provided by a single clinical arterial imaging technique is often insufficient to diagnose vulnerable plaque formation at an early stage. Therefore, an optimal imaging modality for diagnosis and characterization of plaques should combine high spatial resolution capable of resolving fibrous cap thickness, deep imaging depth capable of assessing plaque burden and vessel remodeling, and molecular sensitivity capable of determining tissue composition and mechanical properties.

  2. Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice

    Science.gov (United States)

    Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

    2012-01-01

    Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

  3. Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice

    Directory of Open Access Journals (Sweden)

    D.M. Grosso

    2008-12-01

    Full Text Available In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(- on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/- mice (6 per group were immunized with the following antibodies (100 µg each: mouse anti-LDL(- monoclonal IgG2b, rabbit anti-LDL(- polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25% cholesterol and then every week for 21 days. The passive immunization with anti-LDL(- monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD, respectively compared to control (124.9 ± 13.2 µm². Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(- monoclonal antibody (3.5 ± 0.70 per field x 10 compared to controls (21.5 ± 3.5 per field x 10. Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(- in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU, the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol, and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein. In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.

  4. Association between genetic polymorphisms and carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Radiotherapy (RT) of the neck is commonly given to nasopharyngeal carcinoma (NPC) patients for preventing cervical lymph node metastasis. However, neck RT may induce the development of carotid atherosclerosis. The mechanisms of radiation-induced carotid atherosclerosis are still unclear and no previous study has investigated the genetic involvement of radiation-induced carotid atherosclerosis. The present study aims to determine the association between genetic polymorphisms and carotid atherosclerosis in patients treated with RT for nasopharyngeal carcinoma. The present study recruited 128 post-RT NPC patients. Carotid plaque score was assessed using ultrasonography. Thirteen single nucleotide polymorphisms (SNPs) that affect the function of anti-atherosclerotic genes, including SOD2, SOD3, CAT, PON1, PPARG, ADIPOQ, IL10, TGFB1 and NOS3, were genotyped. Association between the 13 SNPs and carotid atherosclerosis was evaluated using multiple regression after adjustment for covariates (PLINK). Multiple testing was corrected using Benjamini-Hochberg step-up false discovery rate controlling procedure. rs662 and rs705379 of PON1 were close to be significantly associated with carotid plaque score (Corrected P value, Pcor = 0.0528 and Pcor = 0.0842). When the two SNPs were combined together, TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (Pcor < 0.05). None of the other SNPs showed significant association with carotid plaque score. TC haplotype in rs662-rs705379 of PON1 is likely to be a genetic risk factor of carotid plaque score. Post-RT NPC patients with the TC haplotype may need earlier and more frequent carotid ultrasound examinations for early detection of carotid atherosclerosis

  5. Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Getz GS

    2011-06-01

    Full Text Available Godfrey S Getz, Catherine A ReardonThe University of Chicago, Department of Pathology, Chicago, IL, USAAbstract: Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans.Keywords: apoA-I, mimetic peptides, HDL, anti-inflammatory, atherosclerosis

  6. The association between coronary calcification assessed by electron beam computed tomography and measures of extracoronary atherosclerosis - The Rotterdam Coronary Calcification Study

    NARCIS (Netherlands)

    Oei, HHS; Vliegenthart, R; Hak, AE; del Sol, AI; Hofman, A; Oudkerk, M; Witteman, JCM

    2002-01-01

    OBJECTIVES The present study was designed to examine the associations of coronary calcification assessed by electron beam computed tomography (CT) with measures of extracoronary atherosclerosis. BACKGROUND Although measures of extracoronary atherosclerosis have been used to predict coronary events,

  7. Impaired LDL Receptor-Related Protein 1 Translocation Correlates with Improved Dyslipidemia and Atherosclerosis in apoE-Deficient Mice

    DEFF Research Database (Denmark)

    Gordts, Philip L S M; Bartelt, Alexander; Nilsson, Stefan K;

    2012-01-01

    Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE.......Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE....

  8. Skin autofluorescence, a non-invasive marker for AGE accumulation, is associated with the degree of atherosclerosis

    NARCIS (Netherlands)

    den Dekker, Martijn A. M.; Zwiers, Marjan; van den Heuvel, Edwin R.; de Vos, Lisanne C.; Smit, Andries J.; Zeebregts, Clark J.; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Lefrandt, Johan; Mulder, Douwe J.

    2013-01-01

    Introduction: Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with th

  9. Interactions between inflammation and lipid metabolism: Relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis

    NARCIS (Netherlands)

    Diepen, J.A. van; Berbée, J.F.P.; Havekes, L.M.; Rensen, P.C.N.

    2013-01-01

    Dyslipidemia and inflammation are well known causal risk factors the development of atherosclerosis. The interplay between lipid metabolism and inflammation at multiple levels in metabolic active tissues may exacerbate the development of atherosclerosis, and will be discussed in this review. Cholest

  10. [Effect of trimethylglycine on lipid metabolism in experimental atherosclerosis in rabbits].

    Science.gov (United States)

    Panteleĭmonova, T N; Zapadniuk, V I

    1983-01-01

    It has been shown in adult rabbits aged 8 months with experimental cholesterol atherosclerosis that administration of trimethylglycinee in a dose of 0.5 g/kg reduces the elevated content of total and ester-bound cholesterol, beta-lipoproteins, total lipids in the blood serum and that of total cholesterol and triglycerides in the liver. Little toxicity and high efficacy of trimethylglycin in experimental atherosclerosis make this compound prospective in the light of its use as an antisclerotic agent. PMID:6617841

  11. The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Aristoteli, Lina Panayiota; Møller, Holger Jon; Bailey, Brian;

    2006-01-01

    BACKGROUND: CD163 is a monocyte-macrophage lineage specific scavenger receptor that mediates the uptake and clearance of haptoglobin-haemoglobin complexes, and soluble CD163 (sCD163) is also present in plasma. As atherosclerosis involves infiltration by monocyte-derived macrophages, we investigated...... whether sCD163 may act as a marker of coronary atherosclerosis (CAD). METHODS AND RESULTS: Clinical features were identified and plasma was collected from 147 consecutive patients presenting for coronary angiography. Patients were classified as having CAD+, or being free of CAD- haemodynamically...

  12. Decreased natural killer cell activity is associated with atherosclerosis in elderly humans

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.;

    2001-01-01

    -related inflammatory diseases such as atherosclerosis. Elderly people had decreased cytotoxicity per NK cell in short-term but not in long-term assays. Ca2+ independent cytotoxicity was unaltered, and NK cells maintained their cytotoxic responses to interleukin-2 and interferon-alpha signals. The decreased...... cytotoxicity per NK cell was not completely counteracted by increased circulating numbers of NK cells in the blood. Elderly people with severe medical disorders had low numbers of circulating NK cells. Furthermore, elderly people with atherosclerosis had low cytotoxicity per NK cell and a high number...

  13. Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed.

    Science.gov (United States)

    Prasad, Kailash

    2008-03-01

    Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. It is however not known if SDG would produce regression of atherosclerosis. The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis; (ii) if regression is associated with reduction in serum lipids, oxidative stress or both; and (iii) if the duration of treatment has an effect on regression. Rabbits were assigned to five groups: Group I, regular diet (control); Group II, 0.5% cholesterol diet for 2 months (mo); Group III, same as Group II but followed by regular diet for 2 mo; Group IV, same as Group II and followed by regular diet with SDG (20mg x kg body wt(-1) x day(-1) PO) for 2 mo; and Group V, same as Group IV but SDG treatment for an additional 2 mo. Blood samples were collected from rabbits before and at monthly intervals thereafter on their respective diet regimen for measurement of triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for assessment of atherosclerotic lesions, aortic MDA and aortic chemiluminescence (Aortic-CL), a measure of antioxidant reserve. MDA and Aortic-CL provide an index of oxidative stress. Increases in serum TG, TC, LDL-C, HDL-C and the risk ratio TC/HDL-C in Group II were associated with an increase in oxidative stress and development of atherosclerosis (57% of aortic intimal surface covered with lesions). Serum lipids decreased to a similar extent in Groups III-V, however atherosclerotic lesions were 84%, 63% and 44%, respectively in Groups III-V. There were more atherosclerotic lesions in Group III (+48.9%) as compared to Group II. The atherosclerotic lesions decreased by 24% and 45%, respectively in Groups IV and V compared to Group III. The reduction in atherosclerotic lesions was associated

  14. Non-invasive imaging for subclinical coronary atherosclerosis in patients with peripheral artery disease

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Kjaer, Andreas; Hesse, Birger

    2014-01-01

    Patients with peripheral artery disease are at high risk of coronary artery disease. An increasing number of studies show that a large proportion of patients with peripheral artery disease have significant coronary atherosclerosis, even in the absence of symptoms. Although the reported prevalence...... of subclinical coronary artery disease varies widely in patients with peripheral artery disease, it could include more than half of patients. No consensus exists to date on either the rationale for screening patients with peripheral artery disease for coronary atherosclerosis or the optimal algorithm and method...

  15. Enhanced susceptibility of cyclin kinase inhibitor p21 knockout mice to high fat diet induced atherosclerosis

    OpenAIRE

    Khanna Ashwani K

    2009-01-01

    Abstract Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in severe atherosclerosis in a mouse model. p21-/- and strain matched wild type mice were fed with high fat diet for 21 weeks. Analysis for biochemical parameters (cholesterol, triglycerides) in serum and mRNA expression of CD36, HO-1, TGF-β, IFN-γ, TNF-α, PPAR-γ and NADPH oxidase components (p22...

  16. HDL function and subclinical atherosclerosis in juvenile idiopathic arthritis

    Science.gov (United States)

    Mani, Preethi; Uno, Kiyoko; Duong, MyNgan; Wolski, Kathy; Spalding, Steven; Husni, M. Elaine

    2016-01-01

    Background Increasing evidence suggests that inflammation adversely impacts the protective properties of high-density lipoproteins (HDL) and progression of atherosclerosis. The impact of early chronic inflammatory conditions on HDL function and vascular risk has not been well investigated. Methods We compared measures of HDL particle distribution and functionality, in addition to measures of carotid intima-medial thickness (cIMT) in patients with juvenile idiopathic arthritis (JIA) and age matched controls. Results JIA patients demonstrated lower levels of HDL cholesterol [47.0 (40.0, 56.0) vs. 56.0 (53.0, 61.0) mg/dL, P=0.04], total HDL [29.5 (27.9, 32.3) vs. 32.9 (31.6, 36.3) mg/dL, P=0.05] and large HDL [5.1 (3.7, 7.3) vs. 8.0 (6.7, 9.7) mg/dL, P=0.04] particles. In association JIA patients demonstrated greater cholesterol efflux mediated via ATP binding cassette A1 (ABCA1) [17.3% (12.8, 19.7) vs. 10.0% (5.8, 16.0), P=0.05] and less efflux mediated via ATP binding cassette G-1 (ABCG1) [3.2% (2.0, 3.9) vs. 4.8% (3.5, 5.8), P=0.01] and SR-B1 [6.9% (6.0, 8.4) vs. 9.1% (8.6, 10.2), P=0.002] compared with controls. Exposure of macrophages to serum from JIA patients resulted in a smaller increase in mRNA expression of ABCA1 (2.0±0.95 vs. 7.1±5.7 fold increase, P=0.01) and greater increases in expression of ABCG1 [1.4 (0.9, 1.5) vs. 0.8 (0.7, 1.1) fold increase, P=0.04] and SR-B1 (1.3±0.47 vs. 0.7±0.3 fold increase, P=0.001) compared with controls. Arylesterase (128.9±27.6 vs. 152.0±45.2 umoles/min/mL, P=0.04) activity and endothelial cell migration (491.2±68.9 vs. 634.2±227.4 cells/field, P=0.01) were less in JIA patients. No differences in cIMT were observed between JIA patients and controls. Conclusions The presence of JIA was associated with alterations in HDL particle distribution, cholesterol efflux and non-lipid transporting activities. The ultimate implication of these findings for cardiovascular risk requires further investigation. PMID:26885490

  17. Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia

    NARCIS (Netherlands)

    den Hollander, N. C.; Mulder, Douwe J.; Graaff, R.; Thorpe, S. R.; Baynes, J. W.; Smit, Gerrit; Smit, Andries

    2007-01-01

    Introducton: Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from

  18. Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA

    DEFF Research Database (Denmark)

    Skarpengland, Tonje; B. Dahl, Tuva; Skjelland, Mona;

    2016-01-01

    Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BE...

  19. LDL oxidative modification and carotid atherosclerosis : Results of a multicenter study

    NARCIS (Netherlands)

    Nyyssonen, K.; Kurl, S.; Karppi, J.; Nurmi, T.; Baldassarre, D.; Veglia, F.; Rauramaa, R.; de Faire, U.; Hamsten, A.; Smit, A. J.; Mannarino, E.; Humphries, S. E.; Giral, P.; Grossi, E.; Tremoli, E.

    2012-01-01

    Objective: Serum LDL conjugated diene concentration is a marker of oxidative modification of LDL. We investigated the relationship between LDL conjugated dienes and cross-sectional subclinical atherosclerosis assessed by carotid IMT in high-risk subjects of a multicenter study. Methods: Serum LDL co

  20. Paraoxonase genotype, LDL-oxidation and carotid atherosclerosis in male life-long smokers

    NARCIS (Netherlands)

    Himbergen, van T.; Roest, M.; Waart, de F.; Voorbij, H.; Tits, van L.; Stalenhoef, A.

    2004-01-01

    Paraoxonase (PON-1) is a high-density lipoprotein (HDL) associated enzyme that hydrolyzes lipid peroxides in vitro , which may therefore protect against the onset of atherosclerosis. Heavy smokers are more exposed to oxidative stress and hence at high-risk for oxidative modification of LDL. Our hypo

  1. Clinical chemistry of atherosclerosis : Contribution to apolipoprotein-E analysis, public Health and nutricion

    NARCIS (Netherlands)

    Brouwer, Dineke Aletta Johanna

    1999-01-01

    Chapter 1 is meant as a general introduction to atherosclerosis and the ensuing coronary artery disease (CAD). It gives special attention to atherogenesis, lipoprotein metabolism and nutritional factors. The chapter opens with the presentation of an integrated model of atherogenesis with a central r

  2. Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes

    NARCIS (Netherlands)

    van der Feen, C; Neijens, FS; Kanters, SDJM; Mali, WRTM; Stolk, RP; Banga, JD

    2002-01-01

    Aims To determine differences in the anatomic site of atherosclerosis in the lower extremity between patients with and patients without diabetes. Design Cross-sectional study of patients who underwent angiography of both legs because of symptoms of intermittent claudication, rest and/or night pain,

  3. Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zhuo Chen

    2014-01-01

    Full Text Available Tanshinone IIA (Tan II A is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways.

  4. Aortic stiffness is associated with atherosclerosis of the coronary arteries in older adults : the Rotterdam Study

    NARCIS (Netherlands)

    van Popele, Nicole M.; Mattace-Raso, Francesco U. S.; Vliegenthart, Rozemarijn; Grobbee, Diederick E.; Asmar, Roland; van der Kuip, Deirdre A. M.; Hofman, Albert; de Feijter, Pim J.; Oudkerk, Matthijs; Witteman, Jacqueline C. M.

    2006-01-01

    Objective Aortic stiffness can lead to low diastolic blood pressure, thereby possibly limiting coronary perfusion. Therefore, the simultaneous occurrence of both aortic stiffness and coronary atherosclerosis can lead to an increased risk of subendocardial ischaemia. The aim of the present study was

  5. Aortic stiffness is associated with atherosclerosis of the coronary arteries in older adults: the Rotterdam Study

    NARCIS (Netherlands)

    van Popele, N.M.; Mattace-Raso, F.U.S.; Vliegenthart, R.; Grobbee, D.E.; Asmar, R.; van der Kuip, D.A.M.; Hofman, A.; de Feijter, P.J.; Oudkerk, M.; Witteman, J.C.M.

    2006-01-01

    Objective Aortic stiffness can lead to low diastolic blood pressure, thereby possibly limiting coronary perfusion. Therefore, the simultaneous occurrence of both aortic stiffness and coronary atherosclerosis can lead to an increased risk of subendocardial ischaemia. The aim of the present study was

  6. Carotid atherosclerosis in depression and anxiety : Associations for age of depression onset

    NARCIS (Netherlands)

    Seldenrijk, Adrie; Van Hout, Hein P. J.; van Marwijk, Harm W. J.; de Groot, Eric; Gort, Johan; Rustemeijer, Cees; Diamant, Michaela; Penninx, Brenda W. J. H.

    2011-01-01

    Objective. Mental health and cardiovascular disease have been associated, whereas the temporal course and underlying mechanisms are still incompletely understood. Our aims were to examine the presence of subclinical atherosclerosis in subjects with depressive or anxiety disorder, also taking into ac

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

    Science.gov (United States)

    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.

  8. Suppressive impact of anethum graveolens consumption on biochemical risk factors of atherosclerosis in hypercholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    Mahbubeh Setorki

    2013-01-01

    Conclusions: A. graveolens might have some protective values against atherosclerosis and that it significantly affects some biochemical risk factors of this disease. Our findings also confirm the potential harmful effects of oxidized fats and the importance of dietary polyphenols in the meal.

  9. Breast arterial calcification on mammogram: correlation with carotid arterial atherosclerosis on ultrasonogram

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Nam Ju; Suh, Jung Ho [School of Medicine, Ajou Univ., Suwon (Korea, Republic of); Kim, Ji Hyung [College of Medicine, KonYang Univ., Nonsan (Korea, Republic of)

    2002-01-01

    To investigate the incidence of breast arterial calcification in Korean women, and to determine its association with systemic diseases and carotid arterial atherosclerosis. One thousand seven hundred and thirteen female subjects who underwent mammography at a health care center between May 1999 and May 2000 were included in this study. Of the total, 172 were found to have breast arterial calcification, and were classified according to age. The coincidence of hypertension, diabetes mellitus and hyperlipidemia was examined in both the subject group and the control group selected on the same age basis. To investigate the presence and degree of carotid atherosclerosis, sonographic imaging was performed and the findings were compared between the two groups. The incidence of breast arterial calcification showed statistically significant differences according to age, with a higher incidence in older patients (p<0.05). However, there was no statistical difference in the incidence of hypertension, hyperlipidemia, and diabetes mellitus between groups. Carotid atherosclerosis was subjects more prevalent among subjects than in the control group (p<0.05), though there was no statistically significant difference in the degree of luminal stenosis. The most common pathologic cause of breast arterial calcification is arteriosclerosis. Breast arterial calcification is demonstrated at mammography, along with other clinical risk factors for atherosclerosis or coincidental neurologic symptoms. We stress that further evaluation of the carotid artery is necessary.

  10. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten;

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged...

  11. Arterial heparan sulfate is negatively associated with hyperglycemia and atherosclerosis in diabetic monkeys

    Directory of Open Access Journals (Sweden)

    Litwak Kenneth N

    2004-04-01

    Full Text Available Abstract Background Arterial proteoglycans are implicated in the pathogenesis of atherosclerosis by their ability to trap plasma lipoproteins in the arterial wall and by their influence on cellular migration, adhesion and proliferation. In addition, data have suggested an anti-atherogenic role for heparan sulfate proteoglycans and a pro-atherogenic role for dermatan sulfate proteoglycans. Using a non-human primate model for human diabetes, studies examined diabetes-induced changes in arterial proteoglycans that may increase susceptibility to atherosclerosis. Methods Control (n = 7 and streptozotocin-induced diabetic (n = 8 cynomolgous monkeys were assessed for hyperglycemia by measurement of plasma glycated hemoglobin (GHb. Thoracic aortas obtained at necropsy, were extracted with 4 M guanidine HCL and proteoglycans were measured as hexuronic acid. Atherosclerosis was measured by enzymatic analysis of extracted tissue cholesterol. Glycosaminoglycan chains of arterial proteoglycans were released with papain, separated by agarose electrophoresis and analysed by scanning densitometry. Results Tissue cholesterol was positively associated with hexuronic acid content in diabetic arteries (r = .82, p Conclusions These data implicate hyperglycemia induced modifications in arterial proteoglycans that may promote atherosclerosis.

  12. Association of periodontitis with rheumatoid arthritis and atherosclerosis: Novel paradigms in etiopathogeneses and management?

    Directory of Open Access Journals (Sweden)

    Mena Soory

    2010-05-01

    Full Text Available Mena SooryKing’s College London Dental Institute, Denmark Hill, London UKAbstract: There is increasing documentation of a link between inflammatory periodontal disease affecting the supporting structure of teeth, rheumatoid arthritis, and coronary artery disease. Periodontitis is initiated predominantly by Gram-negative bacteria and progresses as a consequence of the host inflammatory response to periodontal pathogens. Lipopolysaccharide, a cell wall constituent stimulates the production of inflammatory cytokines via the activation of signaling pathways perpetuating inflammatory pathogenesis in a cyclical manner in susceptible individuals; with an element of autoimmune stimulation, not dissimilar to the sequential events seen in RA. Periodontitis, also implicated as a risk factor for cardiovascular disease, promotes mechanisms for atherosclerosis by enhancing an imbalance in systemic inflammatory mediators; more direct mechanisms attributed to microbial products are also implicated in both RA and atherogenesis. Severe periodontal disease characterized by clinical and radiographic parameters has been associated with ischemic stroke risk, significant levels of C-reactive protein and serum amyloid A, amongst others common to both periodontitis and atherosclerosis. Existing data supports the hypothesis that persistent localized infection in periodontitis may influence systemic levels of inflammatory markers and pose a risk for RA and atherosclerosis. A common nucleus of activity in their pathogeneses provides novel paradigms of therapeutic targeting for reciprocal benefit.Keywords: periodontitis, RA, atherosclerosis, periodontal pathogens, cytokines, therapeutic targets

  13. Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting RAGE Signaling in Diabetic Atherosclerosis.

    Science.gov (United States)

    Chung, Jihwa; An, Shung Hyun; Kang, Sang Won; Kwon, Kihwan

    2016-01-01

    A naturally occurring bile acid, ursodeoxycholic acid (UDCA), is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, the detailed action mechanisms of UDCA in atherosclerosis are not fully understood. In this study, we demonstrated whether UDCA exerts anti-atherogenic activity in diabetic atherosclerosis by targeting ER stress and "receptor for advanced glycation endproduct" (RAGE) signaling. UDCA markedly reduced ER stress, RAGE expression, and pro-inflammatory responses [including NF-κB activation and reactive oxygen species (ROS) production] induced in endothelial cells (ECs) by high glucose (HG). In particular, UDCA inhibited HG-induced ROS production by increasing the Nrf2 level. In macrophages, UDCA also blocked HG-induced RAGE and pro-inflammatory cytokine expression and inhibited foam cell formation via upregulation of the ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. In the diabetic mouse model, UDCA inhibited atheromatous plaque formation by decreasing ER stress, and the levels of RAGE and adhesion molecules. In conclusion, UDCA exerts an anti-atherogenic activity in diabetic atherosclerosis by targeting both ER stress and RAGE signaling. Our work implicates UDCA as a potential therapeutic agent for prevention or treatment of diabetic atherosclerosis. PMID:26807573

  14. Overexpression of Angiopoietin-Like Protein 4 Protects Against Atherosclerosis Development

    NARCIS (Netherlands)

    Georgiadi, A.; Wang, Y.; Stienstra, R.; Tjeerdema, N.; Janssen, A.; Stalenhoef, A.; Vliet, J.A. van der; Roos, A. de; Tamsma, J.T.; Smit, J.W.; Tan, N.S.; Müller, M.; Rensen, P.C.; Kersten, S.

    2013-01-01

    Objective: Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized

  15. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    2011-01-01

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed eithe

  16. Linking CD11b+ Dendritic Cells and Natural Killer T Cells to Plaque Inflammation in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Miche Rombouts

    2016-01-01

    Full Text Available Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (subpopulations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/− mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+ conventional dendritic cell (cDC subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+ cDC or natural killer T (NKT cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7. This indicates that circulating CD11b+ cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations.

  17. Transgenic mouse models to study the role of APOE in hyperlipidemia and atherosclerosis

    NARCIS (Netherlands)

    Hofker, M.H.; Vlijmen, B.J.M. van; Havekes, L.M.

    1998-01-01

    Transgenic technologies have provided a series of very useful mouse models to study hyperlipidemia and atherosclerosis. Normally, mice carry cholesterol mainly in the high density lipoprotein (HDL) sized lipoproteins, and have low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cho

  18. 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 (TNF-α

  19. GENETIC VARIATION AND DECREASED RISK FOR OBESITY IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Science.gov (United States)

    Our objective was to investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. We tested the association...

  20. Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality

    NARCIS (Netherlands)

    Sijtsma, F.P.C.

    2015-01-01

    Summary belonging to the thesis entitled ‘Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality’ The long history of epidemiologic studies on diet and cardiovascular disease (CVD) has traditionally relied on analysis of specific nutrient

  1. Monocyte chemotactic protein-1 expression in coronary atherosclerosis plaque of sudden coronary death patients

    Institute of Scientific and Technical Information of China (English)

    冯相平

    2006-01-01

    Objective To investigate the expression of monocyte chemotactic protein 1 (MCP-1) in coronary atherosclerosis plaque of sudden coronary death (SCD) patients and the relationship between MCP-1 expression and SCD. Methods Autopsy heart samples (n=90) collected during 2001 - 2003 were divided to SCD group (n=

  2. 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

    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 of atherosclero......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...... of atherosclerosis and inflammation, in the absence or presence of hyperlipidaemia, was assed in wild-type (n = 36) and human apolipoprotein B (apoB) transgenic mice (n = 27) that were fed normal chow or 60% fat for 12 months. RESULTS: Fat-feeding caused obesity, glucose intolerance and elevated plasma leptin...... atherosclerosis in the absence of dyslipidaemia, and that even a moderate level of LDL-C markedly augments this effect....

  3. Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis

    DEFF Research Database (Denmark)

    Ma, Liqun; Zhong, Jian; Zhao, Zhigang;

    2011-01-01

    Activation of transient receptor potential vanilloid type-1 (TRPV1) channels may affect lipid storage and the cellular inflammatory response. Now, we tested the hypothesis that activation of TRPV1 channels attenuates atherosclerosis in apolipoprotein E knockout mice (ApoE(-/-)) but not Apo...

  4. The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis.

    Science.gov (United States)

    Hovland, Anders; Jonasson, Lena; Garred, Peter; Yndestad, Arne; Aukrust, Pål; Lappegård, Knut T; Espevik, Terje; Mollnes, Tom E

    2015-08-01

    Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis.

  5. Sociodemographic correlates of cognition in the multi-ethnic study of atherosclerosis (MESA)

    Science.gov (United States)

    Our objective was to describe the methodology utilized to evaluate cognitive function in the Multi-Ethnic Study of Atherosclerosis (MESA) and to present preliminary results by age, sex, and race/ethnicity. Cross-sectional measurements of a prospective observational cohort. Residents of 6 U.S. commun...

  6. A study on regression of hypercholesterolemic atherosclerosis in rabbits by flax lignan complex.

    Science.gov (United States)

    Prasad, Kailash

    2007-12-01

    Flax lignan complex (FLC) isolated from flaxseed suppresses the development of hypercholesterolemic atherosclerosis. The objectives of this study were to investigate if FLC produces regression of atherosclerosis and if regression is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, control diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (2 months) followed by regular diet (4 months); and group IV, 0.25% cholesterol diet (2 months) followed by regular diet and FLC (4 months). Serum lipids and oxidative stress parameters were measured before and at various intervals thereafter on their respective diets. The aortas were removed at the end of the protocol for assessment of atherosclerotic plaques and oxidative parameters. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Atherosclerotic changes were accelerated in group III, and this was associated with reductions in serum lipids and oxidative stress. Atherosclerotic lesions in group IV were similar to group II, but significantly smaller than those in group III, and were associated with reductions in serum lipids and oxidative stress similar to that in group III. These results indicate that FLC does not produce regression but prevents the acceleration of atherosclerosis due to the removal of cholesterol in the diet. These effects of FLC are not associated with reductions in serum lipids and oxidative stress. PMID:18172225

  7. Association between metabolic syndrome and subclinical coronary atherosclerosis in asymptomatic adults.

    Science.gov (United States)

    Kullo, Iftikhar J; Cassidy, Andrea E; Peyser, Patricia A; Turner, Stephen T; Sheedy, Patrick F; Bielak, Lawrence F

    2004-12-15

    Metabolic syndrome was associated with the presence and quantity of coronary artery calcium, a marker of subclinical coronary atherosclerosis, in 1,129 asymptomatic adults, ages 20 to 79 years, from a community-based study. The association was independent of 10-year risk of coronary heart disease based on the Framingham risk score.

  8. Measurement of arterial wall thickness as a surrogate marker for atherosclerosis

    NARCIS (Netherlands)

    de Groot, E; Hovingh, GK; Wiegman, A; Duriez, P; Smit, AJ; Fruchart, JC; Kastelein, JJP

    2004-01-01

    Large observational studies and atherosclerosis regression trials of lipid-modifying pharmacotherapy have established that intima-media thickness of the carotid and femoral arteries, as measured noninvasively by B-mode ultrasound, is a valid surrogate marker for the progression of atherosclerotic di

  9. Dietary rice protein isolate attenuates atherosclerosis in apoE-deficient mice by upregulating antioxidant enzymes

    Science.gov (United States)

    Rice-based diets may have been reported to protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of rice-based diet was addressed using the apolipopro...

  10. Abnormalities of blood platelets in rabbits with dietary hypercholesterolemia and atherosclerosis

    International Nuclear Information System (INIS)

    Preliminary results are reported from observations of rabbits that were fed a high cholesterol diet to induce atherosclerosis. The purpose of the project was to develop an animal model that would be appropriate to use in the imaging of vascular lesions by positron emission tomography or other techniques

  11. The HDL hypothesis : does high-density lipoprotein protect from atherosclerosis?

    NARCIS (Netherlands)

    Vergeer, Menno; Holleboom, Adriaan G; Kastelein, John J P; Kuivenhoven, Jan Albert

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  12. Hypocoagulability does not protect against atherosclerosis in hemophilia A patients with obesity

    NARCIS (Netherlands)

    Biere-Rafi, S.; Tuinenburg, A.; Haak, B.; Peters, M.; De Groot, E.; Verhamme, P.; Peerlinck, K.; Visseren, F.; Kruip, M.; Gorkom, B.L.-V.; Buller, H.; Gerdes, V.; Schutgens, R.; Kamphuisen, P.

    2011-01-01

    Introduction: Hemophilia A patients have a 50% lower cardiovascular mortality than the general population. Whether this is caused by less atherosclerosis due to hypocoagulability is unclear. We assessed whether hemophilia A patients with obesity, a major atherosclerotic risk factor, have a lower pre

  13. A semantically-aided architecture for a web-based monitoring system for carotid atherosclerosis.

    Science.gov (United States)

    Kolias, Vassileios D; Stamou, Giorgos; Golemati, Spyretta; Stoitsis, Giannis; Gkekas, Christos D; Liapis, Christos D; Nikita, Konstantina S

    2015-08-01

    Carotid atherosclerosis is a multifactorial disease and its clinical diagnosis depends on the evaluation of heterogeneous clinical data, such as imaging exams, biochemical tests and the patient's clinical history. The lack of interoperability between Health Information Systems (HIS) does not allow the physicians to acquire all the necessary data for the diagnostic process. In this paper, a semantically-aided architecture is proposed for a web-based monitoring system for carotid atherosclerosis that is able to gather and unify heterogeneous data with the use of an ontology and to create a common interface for data access enhancing the interoperability of HIS. The architecture is based on an application ontology of carotid atherosclerosis that is used to (a) integrate heterogeneous data sources on the basis of semantic representation and ontological reasoning and (b) access the critical information using SPARQL query rewriting and ontology-based data access services. The architecture was tested over a carotid atherosclerosis dataset consisting of the imaging exams and the clinical profile of 233 patients, using a set of complex queries, constructed by the physicians. The proposed architecture was evaluated with respect to the complexity of the queries that the physicians could make and the retrieval speed. The proposed architecture gave promising results in terms of interoperability, data integration of heterogeneous sources with an ontological way and expanded capabilities of query and retrieval in HIS.

  14. Thrombin inhibition by dabigatran attenuates atherosclerosis in ApoE deficient mice

    OpenAIRE

    Pingel, Simon; Tiyerili, Vedat; Mueller, Jens; Werner, Nikos; Nickenig, Georg; Mueller, Cornelius

    2014-01-01

    Introduction Atherosclerosis is a chronic inflammatory disease characterized by endothelial cell damage, infiltration, proliferation and accumulation of macrophages, lymphocytes and transformed vascular smooth muscle cells within the vascular wall and procoagulation processes involving activation of plasmatic coagulation events and platelets. Numerous studies suggested a close interaction between thrombin action and atherogenesis, but possibly underlying mechanisms are multiple and specific t...

  15. CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rosemeire A. Silva

    2016-08-01

    Full Text Available The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr−/− mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05, when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr−/− mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC was synthesized and labeled with 111InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC, to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases.

  16. Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man

    NARCIS (Netherlands)

    Luchtefeld, Maren; Schunkert, Heribert; Stoll, Monika; Selle, Tina; Lorier, Rachel; Grote, Karsten; Sagebiel, Christian; Jagavelu, Kumaravelu; Tietge, Uwe J. E.; Assmus, Ulrike; Streetz, Konrad; Hengstenberg, Christian; Fischer, Marcus; Mayer, Bjoern; Maresso, Karen; El Mokhtari, Nour Eddine; Schreiber, Stefan; Mueller, Werner; Bavendiek, Udo; Grothusen, Christina; Drexler, Helmut; Trautwein, Christian; Broeckel, Ulrich; Schieffer, Bernhard

    2007-01-01

    Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepat

  17. Mechanism linking atherosclerosis and type 2 diabetes: increased expression of scavenger receptor CD36 in monocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-mei; ZHANG Xiao-lian; ZHOU Xin; LI Dong; GU Jin-gang; WU Juan-juan

    2005-01-01

    Background We investigated the pathogenesis of atherosclerosis in diabetes, and detected the expression of scavenger receptor CD36 in monocytes in patients with type 2 diabetes.Methods According to the criteria by WHO, diabetic patients were classified into two groups: well controlled diabetic patients (WCP) and poorly controlled diabetic patients (PCP). The expression of CD36 protein and mRNA were evaluated by flow cytometry and reversal transcription polymerase chain reaction (RT-PCR). Plasma levels of accumulution of oxidized LDL (oxLDL) were directly measured by sandwich enzyme-linked immunosorbent assay (ELISA) method.Results Flow cytometry and RT-PCR showed that the mean fluorescence intensity (MFI) of CD36 in monocyte and CD36 mRNA were significantly higher in the PCP and WCP in comparison with healthy controls (P0.05). The concentrations of plasma oxLDL were higher in the PCP group compared to WCP and control group (P0.05). In the WCP and PCP groups, oxLDL levels were higher in patients with diabetic atherosclerosis than those without diabetic atherosclerosis (P<0.05).Conclusions The increased expression of scavenger receptor CD36 may be one of the mechanism of accelerated atherosclerosis in diabetic. The poorly controlled diabetes patients are at higher risk for the vascular complications than the well controlled diabetic patients.

  18. High cumulative insulin exposure : a risk factor of atherosclerosis in type 1 diabetes?

    NARCIS (Netherlands)

    Muis, MJ; Bots, ML; Bilo, HJG; Hoogma, RPLM; Hoekstra, JBL; Grobbee, DE; Stolk, RP

    2005-01-01

    Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a potent

  19. Appropriateness of the hamster as a model to study diet-induced atherosclerosis

    Science.gov (United States)

    Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apo...

  20. The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes

    Directory of Open Access Journals (Sweden)

    sasso Ferdinando

    2007-10-01

    Full Text Available Abstract We have reviewed the impact of the ubiquitin proteasome system (UPS on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD. People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin

  1. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    Directory of Open Access Journals (Sweden)

    Brian J Bennett

    2015-12-01

    Full Text Available Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP. The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden and human cholesteryl ester transfer protein (CETP. The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear

  2. Human-like atherosclerosis in minipigs: a new model for detection and treatment of vulnerable plaques.

    Science.gov (United States)

    Thim, Troels

    2010-07-01

    Advanced atherosclerosis, through thrombosis, leads to ischemic heart disease and ischemic stroke, the leading causes of death and disability worldwide. Advanced atherosclerosis and imaging of atherosclerosis are the focus of this dissertation with particular emphasis on the vulnerable plaque and vulnerable plaque detection. Aspects of advanced atherosclerosis and the vulnerable plaque in humans are described along with the basis for the selected minipig models and methods for atherosclerosis acceleration used. The overall aims of the studies were to develop an animal model of advanced atherosclerosis with human like vulnerable plaque morphology and use this animal model to test an imaging modality aimed at vulnerable plaque detection. The first aim is addressed in 3 papers, where accelerated plaque development in the coronary and carotid arteries is investigated in down sized Rapacz pigs. Down-sized Rapacz pigs are minipigs with familial hypercholesterolemia caused by a mutation in the low density lipoprotein receptor. Paper 1 describes the lipid profile in the down-sized Rapacz on chow and atherogenic diets and spontaneously developed and balloon accelerated coronary plaque with a morphology that resembles the morphology of human vulnerable plaque. Paper 2 describes vein graft disease in internal jugular vein grafts inserted into the common carotid artery. Plaques with necrotic cores were found in oversized vein grafts only indicating an effect of flow and shear stress on plaque development. Paper 3 describes the effects of wall shear stress on local plaque development in surgically stenosed common carotid arteries in the down-sized Rapacz pigs. This study indicated that the combination of low and oscillatory wall shear stress was needed for development of advanced plaque. In paper 4, we interrogated coronary lesions in the down-sized Rapacz with a commercially available diagnostic tool VH IVUS. It is claimed that VH IVUS can characterize the tissue components

  3. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    Science.gov (United States)

    Bennett, Brian J; Davis, Richard C; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C; Hazen, Stanley L; Gargalovic, Peter S; Lusis, Aldons J

    2015-12-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  4. Excess exposure to insulin is the primary cause of insulin resistance and its associated atherosclerosis.

    Science.gov (United States)

    Cao, Wenhong; Ning, Jie; Yang, Xuefeng; Liu, Zhenqi

    2011-11-01

    The main goal of this review is to provide more specific and effective targets for prevention and treatment of insulin resistance and associated atherosclerosis. Modern technologies and medicine have vastly improved human health and prolonged the average life span of humans primarily by eliminating various premature deaths and infectious diseases. The modern technologies have also provided us abundant food and convenient transportation tools such as cars. As a result, more people are becoming overfed and sedentary. People are generally ingesting more calories than their bodies' need, leading to the so-called "positive energy imbalance", which is inseparable from the development of insulin resistance and its associated atherosclerosis. A direct consequence of insulin resistance is hyperinsulinemia. The current general view is that insulin is not functional properly in the presence of insulin resistance. Thus, the role of insulin itself in the development of insulin resistance and associated atherosclerosis has not been recognized. We have recently observed that the basal level of insulin signaling is increased in the presence of insulin resistance and hyperinsulinemia. In this review, we will explain how the increased basal insulin signaling contributes to the development of insulin resistance and associated atherosclerosis. We will first explain how insulin causes insulin resistance through two arbitrary stages (before and after the presence of obvious insulin resistance), and, then, explain how the excess exposure to insulin and the relative insulin insufficiency contributes to the atherosclerotic diseases. We propose that blockade of the excess insulin signaling is a viable approach to prevent and/or reverse insulin resistance and its associated atherosclerosis.

  5. Local factors modify the dose dependence of 56Fe-induced atherosclerosis.

    Science.gov (United States)

    Kucik, Dennis; Gupta, Kiran; Wu, Xing; Yu, Tao; Chang, Polly; Kabarowski, Janusz; Yu, Shaohua

    2012-07-01

    Radiation exposure from a number of terrestrial sources is associated with an increased risk of cardiovascular disease, but evidence establishing whether high-LET radiation has similar effects has been lacking. We recently demonstrated that 600 MeV/n 56Fe induces atherosclerosis as well. Ten-week old male apolipoprotein-E deficient mice, a well-characterized atherosclerosis animal model, were exposed to 0 (control) 2, or 5Gy 56Fe targeted to the chest and neck. In these mice, 56Fe-induced atherosclerosis was similar in character to that induced by X-rays in the same mouse model and to that resulting from therapeutic radiation in cancer patients. Atherosclerosis was exacerbated by 56Fe only in targeted areas, however, suggesting a direct effect of the radiation on the arteries themselves. This is in contrast to some other risk factors, such as high cholesterol or tobacco use, which have systemic effects. The radiation dose required to accelerate development of atherosclerotic plaques, however, differed depending on the vessel that was irradiated and even the location within the vessel. For example, atherosclerosis in the aortic arch was accelerated only by the highest dose (5 Gy), while the carotid arteries and the aortic root showed effects at 2 Gy (a dose four- to eight-fold lower than the dose of X-rays that produces similar effects in this model). Since shear stress is disrupted in the area of the aortic root, it is likely that at least part of the site-specificity is due to additive or synergistic effects of radiation and local hydrodynamics. Other factors, such as local oxidative stress or gene expression may also have been involved. Since the pro-atherogenic effects of 56Fe depend on additional local factors, this suggests that radiation exposure, when unavoidable, might be mitigated by modification of factors unrelated to the radiation itself.

  6. Lower zinc bioavailability may be related to higher risk of subclinical atherosclerosis in Korean adults.

    Directory of Open Access Journals (Sweden)

    Su Kyoung Jung

    Full Text Available BACKGROUND: There is a proposed link between dietary zinc intake and atherosclerosis, but this relationship remains unclear. Phytate may contribute to this relationship by influencing zinc bioavailability. OBJECTIVE: The aim of this study is to examine the relationship between zinc bioavailability and subclinical atherosclerosis in healthy Korean adults. MATERIALS AND METHODS: The present cross-sectional analysis used baseline data from the Korean multi-Rural Communities Cohort Study (MRCohort, which is a part of The Korean Genome Epidemiology Study (KoGES. A total of 5,532 subjects (2,116 men and 3,416 women aged 40 years and older were recruited from rural communities in South Korea between 2005 and 2010. Phytate:zinc molar ratio, estimated from a food-based food frequency questionnaire (FFQ of 106 food items, was used to determine zinc bioavailability, and carotid intima media thickness (cIMT and pulse wave velocity (PWV were measured to calculate the subclinical atherosclerotic index. RESULTS: We found that phytate:zinc molar ratio is positively related to cIMT in men. A higher phytate:zinc molar ratio was significantly related to an increased risk of atherosclerosis in men, defined as the 80(th percentile value of cIMT (5(th vs. 1(st quintile, OR = 2.11, 95% CI 1.42-3.15, P for trend = 0.0009, and especially in elderly men (5(th vs. 1(st quintile, OR = 2.58, 95% CI 1.52-4.37, P for trend = 0.0021. We found a positive relationship between phytate:zinc molar ratio and atherosclerosis risk among women aged 65 years or younger. Phytate:zinc molar ratio was not found to be related to PWV. CONCLUSIONS: Lower zinc bioavailability may be related to higher atherosclerosis risk.

  7. Study on the Prevalence and Corelation of Carotid Atherosclerosis in Stroke Patients

    Institute of Scientific and Technical Information of China (English)

    Wei Hua; Wang Yongjun; Yah Zhenying

    2000-01-01

    Objective To assess the prevalence and severity of carotid atherosclerosis in stroke patients and the risk factors of carotid atherosclerosis. Methods Two hundred fifty-one ischemic stroke patients,46 ccrcbral hemorrhagc patients and 96 control subjects were entercd into this study. Sonographic assessment of the extracranial carotid arteries was performed in all patients. Diametcr. IMT, plaques and percentage ratio of lumen stenosis were observcd. Results (1)The prevalence of carotid plaqucs was prominent in stroke patients than the control subjects(63.0%vs 36.5%). (2)The prevalencc of lumen stenosis>50% in ischemic stroke patients was higher than the cerebral hemorrhage patients and control subjects (15.6% vs 4.3%. 2.1%).(3) The prevalence of severe carotid artery stcnosis(>75%) was promincnt in aged 61~70 years old patients.(4)Our data revealed 30% of the cortical infarction subgroup, 17.5%of the subcortical infarction subgroup, 17% of the lacunar infarction subgroup,8% of the vcrtibral-basilar artery infarction subgroup.2.8% of thc CT normal subgroup possessed carotid stcnosis >50%. (5)Age, diabetes mellitus and ApoAl(inversely) were independent predictors of the extracranial carotid atherosclcrosis. Discusssion (Ⅰ)There is close relation between extracraniai carotid atherosclerosis and ischemic cerebrovascular disease.(2)The extent of serious carotid artery stcnosis in aged patients was lower.(3)Thc severity of extracranial carotid artery atherosclerosis was prominent in patients with conical infarction. Conclusion There is a high prevalence of extracranial carotid atherosclerosis in Chinese stroke patients.

  8. Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E.

    Science.gov (United States)

    Hsu, Charlie C; Paik, Jisun; Brabb, Thea L; O'Brien, Kevin D; Kim, Jinkyu; Sullivan, Brittany G; Hudkins, Kelly L; Seamons, Audrey; Finley, Jennifer C; Meeker, Stacey M; Maggio-Price, Lillian

    2015-10-01

    Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes. Therefore, we investigated whether MNV4 likewise altered atherosclerosis in ApoE(-/-) mice. In the presence of oxidized LDL, MNV4 infection of ApoE(-/-) bone marrow-derived macrophages increased the gene expression of the inflammatory markers inducible nitric oxide synthase, monocyte chemoattractant protein 1, and IL6. In addition, proteins involved in cholesterol transport were altered in MNV4-infected ApoE -/- bone marrow-derived macrophages and consisted of increased CD36 and decreased ATP-binding cassette transporter A1. MNV4 infection of ApoE(-/-) mice at 12 wk of age (during the development of atherosclerosis) had a variable effect on atherosclerotic lesion size. In one study, MNV4 significantly increased atherosclerotic plaque area whereas in a second study, no effect was observed. Compared with controls, MNV4-infected mice had higher circulating Ly6C-positive monocytes, and viral RNA was detected in the aortas of some mice, suggesting potential mechanisms by which MNV4 alters disease progression. Plaque size did not differ when ApoE -/- mice were infected at 4 wk of age (early during disease development) or in ApoE -/- mice maintained on a high-fat, high-cholesterol diet. Therefore, these data show that MNV4 has the potential to exert a variable and unpredictable effect on atherosclerosis in ApoE(-/-) mice. We therefore propose that performing experiments in MNV-free mouse colonies is warranted. PMID:26473341

  9. Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden/composition in young adult population

    Directory of Open Access Journals (Sweden)

    Seckin Satilmis

    2015-02-01

    Full Text Available Evidence suggests that low 25-OH vitamin D 25(OHD concentrations may increase the risk of several cardiovascular diseases such as hypertension, peripheral vascular disease, diabetes mellitus, obesity, myocardial infarction, heart failure and cardiovascular mortality. Recent studies suggested a possible relationship between vitamin D deficiency and increased carotid intima-media wall thickness and vascular calcification. We hypothesized that low 25(OHD may be associated with coronary atherosclerosis and coronary plaque burden and composition, and investigated the relationship between serum vitamin D levels and coronary atherosclerosis, plaque burden or structure, in young adult patients by using dual-source 128x2 slice coronary computed tomography angiography (CCTA. We included 98 patients with coronary atherosclerosis and 110, age and gender matched, subjects with normal findings on CCTA examinations. Patients with subclinical atherosclerosis had significantly higher serum total cholesterol, triglycerides, hs-CRP, uric acid, HbA1c and creatinine levels and lower serum 25(OHD levels in comparison with controls. There was no significant correlation between 25(OHD and plaque morphology. There was also a positive relationship between 25(OHD and plaque burden of coronary atherosclerosis. In multivariate analysis, coronary atherosclerosis was associated high hs-CRP (adjusted OR: 2.832, uric acid (adjusted OR: 3.671 and low 25(OHD (adjusted OR: 0.689. Low levels of 25(OHD were associated with coronary atherosclerosis and plaque burden, but there was no significant correlation between 25(OHD and plaque morphology.

  10. Overexpression of NF-κB p65 in macrophages ameliorates atherosclerosis in apoE-knockout mice

    OpenAIRE

    Ye, Xin; Jiang, Xiaoting; Guo, Wei; Clark, Katie; Gao, Zhanguo

    2013-01-01

    The transcription factor NF-κB p65 is a key regulator in the regulation of an inflammatory response and in the pathology of atherosclerosis. However, there is no direct evidence for the role of NF-κB in macrophages in the development of atherosclerosis. We investigated whether macrophage overexpression of p65 in apoE-knockout mice could improve atherosclerosis. Transgenic (Tg) mice overexpressing p65 in macrophages were generated by crossing fatty acid-binding protein 4 (aP2) promoter-control...

  11. ULTRASONOGRAPHIC ASSESSMENT OF COMMON CAROTID ARTERY ATHEROSCLEROSIS IN PATIENTS OF RHEUMATOID ARTHRITIS

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    Jayakumar

    2015-02-01

    Full Text Available BACKGROUND & OBJECTIVES: Patients with Rheumatoid Arthritis (R.A. have a marked increase in Carotid Atherosclerosis independent of traditional risk factors like family history of myocardial infarction in first degree male relatives younger than 55 years of age or first degree female relatives younger than 65 years of age, smoking, hypertension (D efined as blood pressure of 140/90 mm hg or higher, diabetes mellitus and fasting serum cholesterol levels including age. Chronic inflammation and possibly disease severity and duration are atherogenic in Rheumatoid Arthritis patients. Preclinical disease may also be identified by using ultrasonography to determine carotid intimal - media thickness, an indirect measure of atherosclerosis. The common carotid artery Intima media thickness in Rheumatoid Arthritis patients is positively associated with disease duration, Early Rheumatoid Arthritis (D uration less or = 1 year is associated with lesser Intima media thickness than was Rheumatoid Arthritis of longer duration. Increased carotid artery Intima media thickness and the presence of carotid plaque are associated with markers of systemic inflammation in patients with Rheumatoid Arthritis and in healthy subjects. OBJECTIVE OF THE STUDY: To determine preclinical atherosclerosis occurring prematurely in patients of Rheumatoid Arthritis by ultrasonograhic measurement Common Carotid Artery Intima media thickness and to evaluate the risk factors associated with arterial intima media thickness in patient of Rheumatoid Arthritis. RESULTS: In RA patients, common carotid artery IMT was significantly higher when compared to healthy controls (0.65 ± 0.06 v/s 0.57 ± 0.049 and was significantly associated with the duration of RA, swollen joint count and erosive changes on hand x - ray independently of other confounding variables. CONCLUSION: Patients with rheumatoid arthritis have a marked increase in carotid atherosclerosis independent of traditional risk factors

  12. Premature subclinical atherosclerosis in children and young adults with juvenile idiopathic arthritis. A review considering preventive measures

    DEFF Research Database (Denmark)

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

    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...

  13. Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE(-/-) mice.

    Science.gov (United States)

    Chan, Yee Kwan; El-Nezami, Hani; Chen, Yan; Kinnunen, Kristiina; Kirjavainen, Pirkka V

    2016-12-01

    Atherosclerosis results from chronic inflammation potentially caused by translocation of bacterial components from the oro-gastrointestinal tract to circulation. Specific probiotics have anti-inflammatory effects and may reduce bacterial translocation. We thereby tested whether a probiotic mixture with documented anti-inflammatory potential could reduce atherosclerosis. ApoE(-/-) mice were fed high fat diet alone or with VSL#3 or a positive control treatment, telmisartan or both for 12 weeks. All treatments reduced atherosclerotic plaques significantly compared to high fat diet alone. VSL#3 significantly reduced proinflammatory adhesion molecules and risk factors of plaque rupture, reduced vascular inflammation and atherosclerosis to a comparable extent to telmisartan; and VSL#3 treated mice had the most distinctly different intestinal microbiota composition from the control groups. Combining the VSL#3 and telmisartan brought no further benefits. Our findings showed the therapeutic potential of VSL#3 in reducing atherosclerosis and vascular inflammation. PMID:27576894

  14. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

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    Héctor Rincón-Arévalo

    2016-06-01

    Full Text Available Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/− mice fed or not with high-fat diet (HFD, by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410 [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia.

  15. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Science.gov (United States)

    Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A.; Ramírez-Pineda, José R.; Yassin, Lina M.

    2016-01-01

    Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/−) mice fed or not with high-fat diet (HFD), by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410) [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia. PMID:27081674

  16. Is Early Onset Androgenic Alopecia a Marker of Metabolic Syndrome and Carotid Artery Atherosclerosis in Young Indian Male Patients?

    OpenAIRE

    Banger, Harmeet Singh; Malhotra, Suresh Kumar; Singh, Sohan; Mahajan, Mridula

    2015-01-01

    Background: Androgenic alopecia (AGA) is a common cosmetically and psychosocially distressing condition. High androgen level contributes to the development of atherosclerosis, thrombosis leading to hypertension and hypercholesterolemia. Objectives: To study the clinico-epidemiological profile of AGA and the presence of metabolic syndrome (MetS) and carotid artery atherosclerosis in male patients with early onset AGA as compared to controls. Materials and Methods: In this case-control study, 1...

  17. Anti-Inflammatory and Antioxidant Activities of the Nonlipid (Aqueous) Components of Sesame Oil: Potential Use in Atherosclerosis

    OpenAIRE

    Selvarajan, Krithika; Narasimhulu, Chandrakala Aluganti; Bapputty, Reena; Parthasarathy, Sampath

    2015-01-01

    Dietary intervention to prevent inflammation and atherosclerosis has been a major focus in recent years. We previously reported that sesame oil (SO) was effective in inhibiting atherosclerosis in low-density lipoprotein-receptor negative mice. We also noted that the levels of many proinflammatory markers were lower in the SO-treated animals. In this study we tested whether the non-lipid, aqueous components associated with SO would have anti-inflammatory and antioxidant effects. Polymerase cha...

  18. Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

    OpenAIRE

    Halabalaki Maria; Magiatis Prokopios; Chatziioannou Achilles; Papalois Apostolos; Iliopoulos Dimitrios; Karatzas Theodore; Agrogiannis George; Georgopoulou Katerina; Marinou Katerina A; Tsantila Nektaria; Skaltsounis Leandros A; Patsouris Efstratios; Dontas Ismene A

    2010-01-01

    Abstract Background Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the Pistacia vera nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis. Methods and results Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a...

  19. Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4–NF-κB pathway

    OpenAIRE

    Luo, Hong; Jing WANG; Qiao, Chenhui; Ma, Ning; Liu, Donghai; Zhang, Weihua

    2015-01-01

    Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and i...

  20. CD8{sup +}CD25{sup +} T cells reduce atherosclerosis in apoE(−/−) mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jianchang; Dimayuga, Paul C.; Zhao, Xiaoning; Yano, Juliana; Lio, Wai Man; Trinidad, Portia; Honjo, Tomoyuki; Cercek, Bojan; Shah, Prediman K.; Chyu, Kuang-Yuh, E-mail: Chyuk@cshs.org

    2014-01-17

    Highlights: •The role of a sub-population of CD8{sup +} T cells with suppressor functions was investigated in atherosclerosis. •CD8{sup +}CD25{sup +} T cells from adult apoE(−/−) mice had phenotype characteristics of T suppressor cells. •These CD8{sup +}CD25{sup +} T cells reduced CD4{sup +} T cell proliferation and CD8{sup +} cytotoxic activity in vitro. •Adoptive transfer of CD8{sup +}CD25{sup +} T cells significantly reduced atherosclerosis. •CD8{sup +}CD25{sup +} T cells have a suppressive function in atherosclerosis. -- Abstract: Background: It is increasingly evident that CD8{sup +} T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8{sup +}CD25{sup +} T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis were investigated in this study. Methods and results: CD8{sup +}CD25{sup +} T cells were observed in atherosclerotic plaques of apoE(−/−) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8{sup +}CD25{sup +} T cells from apoE(−/−) mice. Depletion of CD8{sup +}CD25{sup +} from total CD8{sup +} T cells rendered higher cytolytic activity of the remaining CD8{sup +}CD25{sup −} T cells. Adoptive transfer of CD8{sup +}CD25{sup +} T cells into apoE(−/−) mice suppressed the proliferation of splenic CD4{sup +} T cells and significantly reduced atherosclerosis in recipient mice. Conclusions: Our study has identified an athero-protective role for CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis.

  1. Ankle brachial index, C-reactive protein, and central augmentation index to identify individuals with severe atherosclerosis

    DEFF Research Database (Denmark)

    Eldrup, Nikolaj; Sillesen, Henrik; Prescott, Eva;

    2006-01-01

    We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease.......We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease....

  2. Association between microalbuminuria and subclinical atherosclerosis evaluated by carotid artery intima-media in elderly patients with normal renal function

    OpenAIRE

    Kong XiangLei; Jia XiaoYan; Wei Yong; Cui MeiYu; Wang ZunSong; Tang LiJun; Li WenBin; Zhu ZhuXian; Chen Ping; Xu DongMei

    2012-01-01

    Abstract Background Moderate to severe renal insufficiency and albuminuria have been shown to be independent risk factors for atherosclerosis. However, little is known about the direct association between subclinical atherosclerosis evaluated by carotid artery intima-media thickness (IMT) and microalbuminuria in elderly patients with normal renal function. Methods Subjects were 272 elderly patients (age  ≥ 60 years) with normoalbuminuria (n = 238) and microalbuminuria (n = 34). Carotid IMT wa...

  3. Impact of local flow haemodynamics on atherosclerosis in coronary artery bifurcations.

    Science.gov (United States)

    Antoniadis, Antonios P; Giannopoulos, Andreas A; Wentzel, Jolanda J; Joner, Michael; Giannoglou, George D; Virmani, Renu; Chatzizisis, Yiannis S

    2015-01-01

    Coronary artery bifurcations are susceptible to atherosclerosis as a result of the unique local flow patterns and the subsequent endothelial shear stress (ESS) environment that are conducive to the development of plaques. Along the lateral walls of the main vessel and side branches, a distinct flow pattern is observed with local low and oscillatory ESS, while high ESS develops at the flow divider (carina). Histopathologic studies have shown that the distribution of plaque at bifurcation regions is related to the local ESS patterns. The local ESS profile also influences the outcome of percutaneous coronary interventions in bifurcation lesions. A variety of invasive and non-invasive imaging modalities have enabled 3D reconstruction of coronary bifurcations and thereby detailed local ESS assessment by computational fluid dynamics. Highly effective strategies for treatment and ultimately prevention of atherosclerosis in coronary bifurcations are anticipated with the use of advanced imaging and computational fluid dynamic techniques.

  4. Effect of Anna Pavala Sindhooram on plasma and aortic lipids in experimental atherosclerosis.

    Science.gov (United States)

    Marita, A R; Shanmugasundaram, K R

    1982-12-01

    The effect of orally administered Anna Pavala Sindhooram (APS), a herbo-mineral Sidha formulation was investigated on experimental atherosclerosis. Rabbits were fed a cholesterol rich (0.5%) diet for 6 months to induce atherosclerosis. These animals were then divided into six groups and given 50 mg of APS powder/day/animal for a further 6 months. At the end of the experimental period the animals were killed, and their plasma and aortic lipid components estimated. Atherosclerotic lesions of the aorta were quantified and examined histologically. Synthesis of lipids using [14C]acetate as a precursor was studied after i.v. injection. APS was found to be hypolipidemic and induced partial regression of rabbit atheroma and decreased lipogenesis. The results indicate that APS may play an anti-atherogenic role if used in larger doses. PMID:7159504

  5. DENTAL INFECTIONS AND THE ATHEROSCLEROSIS RISK IN A SUBPOPULATION OF SOUTH ROMANIA

    Directory of Open Access Journals (Sweden)

    Alexandru Andrei ILIESCU

    2015-06-01

    Full Text Available Periodontal disease and chronic apical periodontitis are considered risk factors for cardiovascular diseases. This cross-sectional study, performed in a subpopulation living in the South area of Romania, investigated the association between the afore-mentioned oral lesions and atherosclerosis. The research was focused on common carotid artery intima-media wall thickness IMT and dislipidemia, in a batch of 30 hypertensive subjects, age 41-50. Over 40% of the patients diagnosed with periodontal disease and/or chronic apical periodontitis developed subclinical atherosclerosis. Associated dyslipidemia to an increased IMT over 0.9 mm in subjects affected by periodontal disease or combined lesions with chronic apical periodontitis might be considered a strong predictor of future cardiovascular events.

  6. Atherosclerosis in low density lipoprotein receptor knockout mice fed cholesterol and soybean oil

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Olsen, P.; Frandsen, H.

    1999-01-01

    In order to study aortic atherosclerosis and atherosclerotic response to dietary cholesterol and soybean oil in homozygous LDLR-/- mice, the 16 weeks old animals were randomized in 4 groups either fed standard diet (no cholesterol added, group I, 12 male and 12 female), standard diet added 0.......9 +/- 0.07 (group III), 32.6 +/-0.1 (group IV), and of females 6.9 +/- 2.7 (group I) and 31.7 +/- 4.4 (group II). No apparent difference in plasma triglyceride levels was observed between the groups of either sexes. Aortic atherosclerosis (ratio intima/media) in males was 0.17 +/- 0.09 (SD) (group I), 0...

  7. Association between atherosclerosis and female lung cancer--a Danish cohort study

    DEFF Research Database (Denmark)

    Dreyer, Lene; Prescott, Eva; Gyntelberg, Finn

    2003-01-01

    identified 2261 1-year survivors of atherosclerotic diseases through 1977 and 1993, while 26150 of the study subjects had no record of an atherosclerotic diagnosis. After linkage to the Danish Cancer Registry associations between atherosclerosis and cancer were analysed for each sex separately by means...... risk of male lung cancer, RR=1.12 (95% CI: 0.77-1.64), or other smoking-related cancers in either sex was observed after multivariate adjustment. Atherosclerosis did not predict non-smoking-related cancers in general in either men, RR=0.91 (95% CI 0.69-1.20), or women, RR=0.93 (95% CI: 0.64-1.35). We...

  8. Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

    Science.gov (United States)

    Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

    2015-07-01

    Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed.

  9. Intimal pericytes as the second line of immune defence in atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Ekaterina; A; Ivanova; Yuri; V; Bobryshev; Alexander; N; Orekhov

    2015-01-01

    Inflammation plays an essential role in the development of atherosclerosis. The initiation and growth of atherosclerotic plaques is accompanied by recruitment of inflammatory and precursor cells from the bloodstream and their differentiation towards pro-inflammatory phenotypes. This process is orchestrated by the production of a number of pro-inflammatory cytokines and chemokines. Human arterial intima consists of structurally distinct leaflets, with a proteoglycan-rich layer lying immediately below the endothelial lining. Recent studies reveal the important role of stellate pericyte-like cells(intimal pericytes) populating the proteoglycan-rich layer in the development of atherosclerosis. During the pathologic process, intimal pericytes may participate in the recruitment of inflammatory cells by producing signalling molecules and play a role in the antigen presentation. Intimal pericytes are also involved in lipid accumulation and the formation of foam cells. This review focuses on the role of pericytelike cells in the development of atherosclerotic lesions.

  10. Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

    Directory of Open Access Journals (Sweden)

    Alma Zernecke

    2014-01-01

    Full Text Available Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis.

  11. Vector flow imaging of the ascending aorta. Are systolic backflow and atherosclerosis related?

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse; Kjaergaard, Jesper;

    2015-01-01

    In the ascending aorta, atherosclerotic plaque formation, which is a risk factor for cerebrovascular events, most often occurs along the inner curvature. Atherosclerosis is a multifactorial disease, but the predilection site for the aortic vessel degradation is probably flow dependent. To better...... understand the aortic flow and especially the complex flow patterns, the ascending aorta was scanned intraoperatively in patients undergoing heart surgery using the angle-independent vector velocity ultrasound method Transverse Oscillation (TO). The primary aim of the study was to analyze systolic backflow...... in relation to atherosclerosis. Thirteen patients with normal aortic valves were included in to the study. TO implemented on a conventional US scanner (ProFocus 2202 UltraView, BK Medical, Herlev, Denmark) with a linear array transducer (8670, BK Medical, Herlev, Denmark) was used intraoperatively...

  12. Association Between Kidney Dysfunction and Carotid Atherosclerosis in Community-Based Older Adults in China.

    Science.gov (United States)

    Gu, Xiang; Fang, Xianghua; Hua, Yang; Tang, Zhe; Ji, Xunming; Guan, Shaochen; Wu, Xiaoguang; Liu, Hongjun; Liu, Beibei; Wang, Chunxiu; Zhang, Zhongying

    2016-03-01

    We investigated the association between kidney dysfunction and carotid atherosclerosis in community-based older adults. This study consisted of 1257 participants, aged 55 years and older and free of cardiovascular disease. Kidney dysfunction was classified as mild, moderate, and severe (estimated glomerular filtration rate, 45-59, 30-44, and kidney function (P kidney dysfunction was significantly associated with CCA-IMT thickening (CCA-IMT ≥1.0 mm; odds ratio [OR] 1.52; 95% confidence interval [CI] 1.16-1.99) compared to normal kidney function. A significantly increased presence of heterogeneous plaque was observed in relation to decreased kidney function (P for trend = .011), that is, even a mild kidney dysfunction was a potential independent risk factor for heterogeneous plaque (OR 1.43; 95% CI 1.04-1.98). Mild kidney dysfunction may be a predictor of early or accelerated carotid atherosclerosis in older adults.

  13. Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke;

    2013-01-01

    Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu......Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular...... and cellular levels in living systems, this technology represents an opportunity to investigate some of these questions in vivo. In addition, molecular imaging may be translated into clinical use and eventually pave the way for more personalized treatment regimes in patients. Here, we review the current...

  14. Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S; Carreira, Ricardo J; van Zeijl, Rene J M; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-08-01

    The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass spectrometry imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin β4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis. PMID:26079611

  15. Obstructive airway disease and edentulism in the atherosclerosis risk in communities (ARIC) study

    OpenAIRE

    Offenbacher, Steven; Beck, James D.; Barros, Silvana P; Suruki, Robert Y; Zvi G Loewy

    2012-01-01

    Objectives We examined the potential association between prior chronic obstructive pulmonary disease (COPD) and edentulism, and whether the association varied by COPD severity using data from the Dental Atherosclerosis Risk in Communities Study. Design Cross-sectional. Setting Community dwelling subjects from four US communities. Participants and measurements Cases were identified as edentulous (without teeth) and subjects with one or more natural teeth were identified as dentate. COPD cases ...

  16. Protective effects of Arctium lappa L. root extracts (AREs) on high fat diet induced quail atherosclerosis

    OpenAIRE

    Wang, Zhi; Li, Ping; Wang, Chenjing; Jiang, Qixiao; Zhang, Lei; Cao, Yu; Zhong, Weizhen; Wang, Chunbo

    2016-01-01

    Background This study was designed to evaluate the protective effects of Arctium lappa L. root extracts (AREs) from different extraction methods (aqueous, ethanol, chloroform and flavone) on atherosclerosis. Methods Quails (Coturnix coturnix) were subjected to high fat diet, with or without one of the four different AREs or positive control simvastatin. Blood samples were collected before treatment, after 4.5 weeks or ten weeks to assess lipid profile (Levels of total cholesterol (TC), Triacy...

  17. Atherosclerosis of Coronary Arteries as Predisposing Factor in Myocardial Infarction: An Autopsy Study

    OpenAIRE

    Gauravi A Dhruva,; Amit H Agravat; Hardik K Sanghvi

    2012-01-01

    The incidence of coronary heart disease has markedly increased in India over the past few years. Ischemic heart disease, the largest cause of morbidity and mortality in the developed and developing countries today is overwhelmingly contributed by atherosclerosis. The study highlights the impact of atherosclerotic lesions in the population of Rajkot district. We studied atherosclerotic lesions in coronary arteries in cases subjected to autopsy in last 4 years, to grade and to evaluate the athe...

  18. Relationship between serum adiopocyte fatty acid binding protein and atherosclerosis in chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    吴晶

    2014-01-01

    Objective To investigate the expression of serum adiopocyte fatty acid binding protein(A-FABP)in chronic kidney disease(CKD)and the role that A-FABP plays in CKD with atherosclerosis.Methods A total of 138 patients with CKD and 20 health control volunteers(HC)were involved in this study.The levels of serum AFABP,free fatty acid(FFA),interleukin-6(IL-6),

  19. Associations of Neighborhood Characteristics with Sleep Timing and Quality: The Multi-Ethnic Study of Atherosclerosis

    OpenAIRE

    De Santis, AS; Roux, AVD; Moore, K; Baron, KG; Mujahid, MS; Javier Nieto, F

    2013-01-01

    Study Objectives: To investigate the associations of specifc neighborhood features (disorder, safety, social cohesion, physical environment, and socioeconomic status) with sleep duration and quality. Design: Cross-sectional. One wave of a population-based study (Multi-Ethnic Study of Atherosclerosis). Setting: Community-dwelling participants in New York, NY and Los Angeles, CA. Participants: There were 1,406 participants (636 males, 770 females). Interventions: NA. Measurements and Results: S...

  20. Inhibition of nuclear factor of activated T-cells (NFAT suppresses accelerated atherosclerosis in diabetic mice.

    Directory of Open Access Journals (Sweden)

    Anna V Zetterqvist

    Full Text Available OBJECTIVE OF THE STUDY: Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: Streptozotocin (STZ-induced diabetes in apolipoprotein E(-/- mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. CONCLUSIONS: Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications.

  1. Cell-free nucleic acids as a non-invasive route for investigating atherosclerosis.

    Science.gov (United States)

    Cerne, Darko; Bajalo, Jana Lukac

    2014-01-01

    Metabolic syndrome is directly linked with atherosclerotic burden and cell-free nucleic acids (cf-NA) analysis has recently emerged as a novel research tool in atherosclerosis practice and research. cf-NA are nucleic acids (DNA, mRNA, miRNA, mitochondrial DNA) found in plasma and cell-free fractions of various other biological fluids. They have all the characteristics of the nucleic acids in the cells of their origin, thus constituting an emerging field for non-invasive assessment. Initially, quantitative and qualitative analysis of cf-NA has been accepted as clinically useful in non-invasive prenatal diagnosis, and in the diagnosis and monitoring of numerous cancers. As to atherosclerosis, cf-NA analysis poses an important challenge in diagnosis and prognostic evaluation of acute coronary syndrome, in prediction of cardiovascular disease, in non-invasive early detection of atherosclerosis and understanding its pathological mechanism in vivo, in assessing various issues of treatment for atherosclerosis in vivo, and in the unique simultaneous measurement of mRNA levels and protein concentrations in a single sample of plasma. Examples of its use are presented in this review. Besides the advances in technologies, the precise evaluation and optimization of pre-analytical and analytical aspects of cf-NA analysis have impacted importantly on the reliability of test results. We have, therefore, reviewed the most important analytical considerations. Further clinical studies and analytical improvements will answer the question as to whether cf-NA, as novel biomarkers, can be reliably applied clinically in non-invasive, early diagnosis and monitoring of the vulnerable atherosclerotic plaques of patients who could suffer from acute coronary syndrome. PMID:24320033

  2. Studi Penentuan Kecepatan Aliran Darah dan Frekuensi Terimaan Pasien Atherosclerosis Menggunakan USG Color Doppler

    OpenAIRE

    Mulyani, Emba

    2014-01-01

    Jurnal Fisika Medik Studi Penentuan Kecepatan Aliran Darah dan Frekuensi Terimaan Pasien Atherosclerosis Menggunakan USG Color Doppler Mulyani H211 08 507 Pembimbing Utama Sri Dewi Astuty Ilyas,Ssi, Msi Nip.19750513 199903 2 001 Pembimbing Pertama Dahlang Tahir, Msi, Ph.D Nip.19750907 200003 1 001 ABSTRACT Research about Study of determination blood speed of current and freq uency give patient atherosclero sis uses plane USG Color Doppler had be...

  3. Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis.

    Directory of Open Access Journals (Sweden)

    Patrick Horn

    Full Text Available Circulating microparticles (MPs derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC by computed tomography. Thrombin-antithrombin complex (TATc levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs, endothelial-derived MPs (EMPs and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.

  4. Emodin inhibits dietary induced atherosclerosis by antioxidation and regulation of the sphingomyelin pathway in rabbits

    Institute of Scientific and Technical Information of China (English)

    HEI Zi-qing; HUANG He-qing; TAN Hong-mei; LIU Pei-qing; ZHAO Ling-zhi; CHEN Shao-rui; HUANG Wen-ge; CHEN Feng-ying; GUO Fen-fen

    2006-01-01

    @@ Emodin is an important component of rhubarb, a traditional Chinese herb. Previous studies in vitro showed that emodin inhibited the proliferation of human vascular smooth muscle cells,1 indicating the possible inhibitive effect of emodin on atherosclerosis. The present research evaluated the effect of emodin on the formation of atherosclerotic lesion induced by high cholesterol and fat diet in rabbits and the mechanism of this effect.

  5. [Cholagogic effect of trimethylglycine in normal animals of different ages and in experimental atherosclerosis].

    Science.gov (United States)

    Zapadniuk, V I; Panteleĭmonova, T N

    1987-07-01

    Trimethylglycine at a dose of 1.5 g/kg was found to produce marked bile secretory effect in young and old rats. In rabbits with experimental atherosclerosis, trimethylglycine increased the content of biliary acids in the bile and normalized the indexes of lipid metabolism in the blood serum. Apparently, the effect on cholesterol transformation into biliary acids and its excretion with the bile is one of the mechanisms of anti-atherosclerotic action of trimethylglycine. PMID:3620644

  6. Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

    OpenAIRE

    Mari Levula; Niku Oksala; Nina Airla; Rainer Zeitlin; Juha-Pekka Salenius; Otso Järvinen; Maarit Venermo; Teemu Partio; Jukka Saarinen; Taija Somppi; VeliPekka Suominen; Jyrki Virkkunen; Juha Hautalahti; Reijo Laaksonen; Mika Kähönen

    2012-01-01

    BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arterie...

  7. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production

    OpenAIRE

    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A.; Zhou, Zhou; Sun, Lijie; Mathison, Angela J.; Garcia-Barrio, Minerva T.; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J; Rader, Daniel J; Urrutia, Raul

    2015-01-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the ...

  8. Targeted Disruption of LDLR Causes Hypercholesterolemia and Atherosclerosis in Yucatan Miniature Pigs

    OpenAIRE

    Bryan T Davis; Xiao-Jun Wang; Rohret, Judy A.; Struzynski, Jason T.; Merricks, Elizabeth P.; Dwight A Bellinger; Rohret, Frank A.; Nichols, Timothy C.; Rogers, Christopher S.

    2014-01-01

    Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR) gene in an effort to provide an improved large animal model of familial hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models b...

  9. Traveling Wave Solutions of Reaction-Diffusion Equations Arising in Atherosclerosis Models

    Directory of Open Access Journals (Sweden)

    Narcisa Apreutesei

    2014-05-01

    Full Text Available In this short review article, two atherosclerosis models are presented, one as a scalar equation and the other one as a system of two equations. They are given in terms of reaction-diffusion equations in an infinite strip with nonlinear boundary conditions. The existence of traveling wave solutions is studied for these models. The monostable and bistable cases are introduced and analyzed.

  10. Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression

    DEFF Research Database (Denmark)

    Tsimikas, Sotirios; Miyanohara, Atsushi; Hartvigsen, Karsten;

    2011-01-01

    We sought to assess the in vivo importance of scavenger receptor (SR)-mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibod...... antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis....

  11. Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits

    Institute of Scientific and Technical Information of China (English)

    GUO Yi; WANG Qi-zhang; TANG Bing-shan; ZUO Yan-fang; LI Fang-ming; JIANG Xin; WANG Ling; MA Ke-fu

    2006-01-01

    Background Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet.Methods Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS 10.0.Results The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6± 13.7)% and (36.3± 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P<0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group.Conclusion The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.

  12. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

    OpenAIRE

    Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.

    2013-01-01

    Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a micr...

  13. Citrullus lanatus 'sentinel' (watermelon) extract reduces atherosclerosis in LDL receptor-deficient mice.

    Science.gov (United States)

    Poduri, Aruna; Rateri, Debra L; Saha, Shubin K; Saha, Sibu; Daugherty, Alan

    2013-05-01

    Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar 'sentinel,' on hypercholesterolemia-induced atherosclerosis in mice. Male low-density lipoprotein receptor-deficient mice at 8 weeks old were given either C. lanatus 'sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water while being fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus 'sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus 'sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake and in urine output between the two groups. C. lanatus 'sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate-/low-density lipoprotein cholesterol. Plasma concentrations of monocyte chemoattractant protein-1 and interferon-gamma were decreased and those of interleukin-10 were increased in mice consuming C. lanatus 'sentinel' extract. Intake of C. lanatus 'sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus 'sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

  14. Fructose metabolism and relation to atherosclerosis, type 2 diabetes, and obesity

    OpenAIRE

    Astrid Kolderup; Birger Svihus

    2015-01-01

    A high intake of sugars has been linked to diet-induced health problems. The fructose content in sugars consumed may also affect health, although the extent to which fructose has a particularly significant negative impact on health remains controversial. The aim of this narrative review is to describe the body’s fructose management and to discuss the role of fructose as a risk factor for atherosclerosis, type 2 diabetes, and obesity. Despite some positive effects of fructose, such as high rel...

  15. Emotional intelligence and coronary atherosclerosis: exploratory study using the Trait Meta-Mood Scale

    OpenAIRE

    Mariana Suárez-Bagnasco; Guillermo Ganum; Miguel Cerdá

    2013-01-01

    Introduction There are no prior studies that assess emotional intelligence in asymptomatic adults with coronary atherosclerosis. Aim The purpose of this study is to explore associations between emotional intelligence in asymptomatic adults with and without coronary atherosclerotic lesions. Design and method Cross-sectional design. The sample consisted of 100 asymptomatic 30 to 80 year-old adults that met the inclusion and exclusion criteria and who underwent coronary multisli...

  16. Deficiency of TDAG51 Protects Against Atherosclerosis by Modulating Apoptosis, Cholesterol Efflux, and Peroxiredoxin‐1 Expression

    OpenAIRE

    Hossain, Gazi S.; Lynn, Edward G.; Maclean, Kenneth N.; Zhou, Ji; Dickhout, Jeffrey G.; Lhoták, Šárka; Trigatti, Bernardo; Capone, John; Rho, Jaerang; Tang, Damu; McCulloch, Christopher A.; Al‐Bondokji, Imtisal; Malloy, Mary J.; Pullinger, Clive R.; Kane, John P.

    2013-01-01

    Background Apoptosis caused by endoplasmic reticulum (ER) stress contributes to atherothrombosis, the underlying cause of cardiovascular disease (CVD). T‐cell death‐associated gene 51 (TDAG51), a member of the pleckstrin homology‐like domain gene family, is induced by ER stress, causes apoptosis when overexpressed, and is present in lesion‐resident macrophages and endothelial cells. Methods and Results To study the role of TDAG51 in atherosclerosis, male mice deficient in TDAG51 and apolipopr...

  17. The relation of antemortem factors to atherosclerosis at autopsy. The Puerto Rico Heart Health Program.

    OpenAIRE

    Sorlie, P. D.; Garcia-Palmieri, M. R.; Castillo-Staab, M. I.; Costas, R.; Oalmann, M. C.; Havlik, R

    1981-01-01

    Among 9824 Puerto Rican men, aged 35-79, participating in a prospective study of cardiovascular risk factors, there were 970 deaths during the period 1965-1977. About 14%, or 139, of these deaths had a protocol autopsy following the procedures of the International Atherosclerosis Project. The percentage of involvement with raised atherosclerotic lesions in the coronary arteries was higher in the urban deceased than in the rural. The coronary heart disease death rate was also found to be highe...

  18. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

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    Svati H Shah

    2009-01-01

    Full Text Available Neuropeptide Y (NPY is a strong candidate gene for coronary artery disease (CAD. We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families, we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004 in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72, family-based association of this block with CAD (p = 0.02, and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05, showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09; and (b GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02. A promoter SNP (rs16147 within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04. To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03. Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

  19. Circulating MiRNA biomarkers serve as a fingerprint for diabetic atherosclerosis.

    Science.gov (United States)

    Zhang, Jing-Yun; Gong, Ying-Lan; Li, Chun-Jun; Qi, Qi; Zhang, Qiu-Mei; Yu, De-Min

    2016-01-01

    Type 2 diabetes mellitus induced atherosclerosis (DA) is regarded as a major cause of disability and death in diabetic patients. The early prediction of atherosclerosis in patients DM is necessary. Therefore, we aimed to identify special plasma microRNAs that can serve as a novel non-invasive screening signature of DA patients with atherosclerosis and test its specificity and sensitivity in the early diagnosis of DA. In total, we obtained plasma samples from 285 diabetic atherosclerosis patients and matched diabetic retinopathy (DR) patients, diabetic nephropathy (DN) patients, diabetes mellitus without complication (DM) and healthy controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). Three miRNAs were significantly increased in patients with DA compared with other groups after the multiple stages. The areas under the receiver operating characteristic (AUC) curves of the validated three-plasma miRNAs signature in DA comparing with NC were 0.881, 0.709 and 0.842 while the merged was 0.940 while DA comparing with DM was 0.879, 0.663, 0.731 and the merged was 0.928. The three miRNA could also distinguish DA from DN with an AUC of 0.894, 0.782, 0.910 and 0.963 (merged) as well as from DR with an AUC of 0.876, 0.815, 0.850 and 0.925 (merged). In conclusion, these data provide evidence that plasma miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of DA. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of DA from DR, DN, DM patients. PMID:27398148

  20. Are Immigrant Enclaves Healthy Places to Live? The Multi-ethnic Study of Atherosclerosis

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    Osypuk, Theresa L.; Roux, Ana V. Diez; Hadley, Craig; Kandula, Namratha

    2009-01-01

    The growing size and changing composition of the foreign born population in the USA highlights the importance of examining the health consequences of living in neighborhoods with higher proportions of immigrants. Using data from the Multiethnic Study of Atherosclerosis in four US cities, we examined whether neighborhood immigrant composition was associated with health behaviors (diet, physical activity) among Hispanic and Chinese Americans (n=1902). Secondarily we tested whether neighborhoods...

  1. 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.

  2. Enhanced susceptibility of cyclin kinase inhibitor p21 knockout mice to high fat diet induced atherosclerosis

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    Khanna Ashwani K

    2009-07-01

    Full Text Available Abstract Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in severe atherosclerosis in a mouse model. p21-/- and strain matched wild type mice were fed with high fat diet for 21 weeks. Analysis for biochemical parameters (cholesterol, triglycerides in serum and mRNA expression of CD36, HO-1, TGF-β, IFN-γ, TNF-α, PPAR-γ and NADPH oxidase components (p22phox, NOX-1 and Rac-1 was performed in aortic tissues by Real Time PCR. p21-/- mice gained significantly (p -/- compared to wild type mice fed with high fat diet. High fat diet resulted in significantly decreased TGF-β (p -/- mice compared to animal fed with regular diet. IFN-γ mRNA expression (235 ± 11 folds increased significantly in high fat diet fed p21-/- mice and a multifold modulation of PPAR-γ(136 ± 7, p22phox, NOX-1 and Rac-1 (15–35-folds mRNA in aortic tissues from p21-/- mice compared to the wild type mice. Severity of atherosclerotic lesions was significantly higher in p21-/- compared to wild type mice. The results demonstrate that the deficiency of p21 leads to altered expression of pro-atherogenic genes, and severe atherosclerosis in mice fed with high fat diet. This opens the possibility of p21 protein as a therapeutic tool to control progression of atherosclerosis.

  3. Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

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    Jun-ichi Kawabe

    2014-01-01

    Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

  4. Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus

    Science.gov (United States)

    Stanic, Aleksandar K.; Stein, Charles M.; Morgan, Adam C.; Fazio, Sergio; Linton, MacRae F.; Wakeland, Edward K.; Olsen, Nancy J.; Major, Amy S.

    2006-01-01

    Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. The underlying mechanisms are poorly understood, and investigations have been hampered by the absence of animal models that reflect the human condition of generalized atherosclerosis and lupus. We addressed this problem by transferring lupus susceptibility to low-density lipoprotein (LDL) receptor-deficient (LDLr−/−) mice, an established model of atherosclerosis, creating radiation chimeras with NZM2410-derived, lupus-susceptible, B6.Sle1.2.3 congenic or C57BL/6 control donors (LDLr.Sle and LDLr.B6, respectively). LDLr.Sle mice developed a lupus-like disease characterized by production of double-stranded DNA autoantibodies and renal disease. When fed a Western-type diet, LDLr.Sle chimeras had increased mortality and atherosclerotic lesions. The plaques of LDLr.Sle mice were highly inflammatory and contained more CD3+ T cells than controls. LDLr.Sle mice also had increased activation of CD4+ T and B cells and significantly higher antibody to oxidized LDL and cardiolipin. Collectively, these studies demonstrate that the lupus-susceptible immune system enhances atherogenesis and modulates plaque composition. PMID:16636270

  5. Antioxidant effect of nondigestible levan and its impact on cardiovascular disease and atherosclerosis.

    Science.gov (United States)

    Dahech, Imen; Harrabi, Bahira; Hamden, Khaled; Feki, Abdelfattah; Mejdoub, Hafedh; Belghith, Hafedh; Belghith, Karima Srih

    2013-07-01

    Levan polysaccharide, a type of fructan, has been shown to favorably affect diabetes type 2 and hypercholesterolemia. Recent reports have indicated that excessive oxidative stress contributes to the development of atherosclerosis linked metabolic syndrome. The objective of this current study was to investigate the possible protection against oxidative stress linked atherosclerosis. A group of twenty four male rats was divided into four subgroups; a normal diet group (Control), normal rats received levan (L), a high-cholesterol diet group (Chol) and a high-cholesterol diet with 5% (w/w) levan group. After the treatment period, the plasma antioxidant enzymes and lipid profiles were determined. Our results show that treatment with levan positively changed plasma antioxidant enzyme activities by increasing superoxide dismutase (SOD) and catalase (CAT) by 40% and 28%, respectively, in heart. Similarly, the treatment of Chol fed groups with levan positively changed lipid profiles by decreasing total cholesterol, triglycerides and LDL-cholesterol by 50%, 38.33% and 64%, respectively. Thus may have potential antioxidant effects and could protect against oxidative stress linked atherosclerosis. PMID:23624165

  6. Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients

    Science.gov (United States)

    Vargas-Robles, Hilda; Serrano, Alberto Maceda; Lozano-Nuevo, Jose Juan; Escalante-Acosta, Bruno Alfonso

    2009-01-01

    Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in normotensive type-2 diabetic patients. Results: We found significant correlations between ICAM-1 (r = 0.69, p < 0.001 95% IC 0.65 to 0.82) and VCAM-1 (r = 0.4, p < 0.03, 95% IC 0.65 to 0.82) levels and maximal carotid artery intimal-medial thickness, whereas no correlation was observed with E-selectin. Methods: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. Conclusion: Our results suggest that ICAM-1 and VCAM-1 are markers associated, and correlated with the degree of atherosclerosis in normotensive type-2 diabetic patients. PMID:19717975

  7. A Pathological Study of the Epidemiology of Atherosclerosis in Mexico City

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    Joel Rodríguez-Saldaña

    2014-01-01

    Full Text Available Objective. To examine the frequency and patterns of association of cardiovascular risk factors with atherosclerosis in five different arterial territories at post-mortem in Mexico City. Methods. We obtained five arterial territories arteries (circle of Willis, coronary, carotid, renal, and aorta of 185 men and women 0 to 90 years of age who underwent autopsy at the Medical Forensic Service of Mexico City. We determined the prevalence and extent of atherosclerotic lesions by histopathology according to the classification of the American Heart Association as early (types I–III and advanced (types IV–VI, and according to the degree of stenosis and correlated with cardiovascular risk factors. Results. Atherosclerotic lesions were identified in at least one arterial territory in 181 subjects (97.8%, with involvement of two ore more territories in 178 subjects (92.2%. Advanced lesions were observed in 36% and 67% of subjects under 15 and between 16 and 35 years, respectively. Any degree of atherosclerosis was associated with the presence of diabetes mellitus, hypertension, overweight, obesity, and smoking, and to a greater extent with the presence of two or more risk factors (P<0.001. However, emerging and advanced athersoclerosis was observed in 53% and 20% people with no risk factors. Conclusions. The study shows a high prevalence of atherosclerosis in all age groups and both sexes. There is considerable development of atherosclerotic disease in subjects without known risk factors.

  8. Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation.

    Science.gov (United States)

    Çimen, Ismail; Kocatürk, Begüm; Koyuncu, Seda; Tufanlı, Özlem; Onat, Umut I; Yıldırım, Asli D; Apaydın, Onur; Demirsoy, Şeyma; Aykut, Zaliha G; Nguyen, Uyen T; Watkins, Steven M; Hotamışlıgil, Gökhan S; Erbay, Ebru

    2016-09-28

    De novo lipogenesis (DNL), the conversion of glucose and other substrates to lipids, is often associated with ectopic lipid accumulation, metabolic stress, and insulin resistance, especially in the liver. However, organ-specific DNL can also generate distinct lipids with beneficial metabolic bioactivity, prompting a great interest in their use for the treatment of metabolic diseases. Palmitoleate (PAO), one such bioactive lipid, regulates lipid metabolism in liver and improves glucose utilization in skeletal muscle when it is generated de novo from the obese adipose tissue. We show that PAO treatment evokes an overall lipidomic remodeling of the endoplasmic reticulum (ER) membranes in macrophages and mouse tissues, which is associated with resistance of the ER to hyperlipidemic stress. By preventing ER stress, PAO blocks lipid-induced inflammasome activation in mouse and human macrophages. Chronic PAO supplementation also lowers systemic interleukin-1β (IL-1β) and IL-18 concentrations in vivo in hyperlipidemic mice. Moreover, PAO prevents macrophage ER stress and IL-1β production in atherosclerotic plaques in vivo, resulting in a marked reduction in plaque macrophages and protection against atherosclerosis in mice. These findings demonstrate that oral supplementation with a product of DNL such as PAO can promote membrane remodeling associated with metabolic resilience of intracellular organelles to lipid stress and limit the progression of atherosclerosis. These findings support therapeutic PAO supplementation as a potential preventive approach against complex metabolic and inflammatory diseases such as atherosclerosis, which warrants further studies in humans. PMID:27683551

  9. Serum carotenoids reduce progression of early atherosclerosis in the carotid artery wall among Eastern Finnish men.

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    Jouni Karppi

    Full Text Available BACKGROUND: Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids. METHODS: We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between concentrations of serum carotenoids, and intima-media thickness of the common carotid artery wall was explored in 840 middle-aged men (aged 46-65 years from Eastern Finland. Ultrasonography of the common carotid arteries were performed at baseline and 7-year follow-up. Serum levels of carotenoids were analyzed at baseline. Changes in mean and maximum intima media thickness of carotid artery wall were related to baseline serum carotenoid levels in covariance analyses adjusted for covariates. RESULTS: In a covariance analysis with adjustment for age, ultrasound sonographer, maximum intima media thickness, examination year, body mass index, systolic blood pressure, smoking, physical activity, serum LDL cholesterol, family history of coronary heart disease, antihypertensive medication and serum high sensitivity C-reactive protein, 7-year change in maximum intima media thickness was inversely associated with lycopene (p = 0.005, α-carotene (p = 0.002 and β-carotene (p = 0.019, respectively. CONCLUSIONS: The present study shows that high serum concentrations of carotenoids may be protective against early atherosclerosis.

  10. Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk

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    Leigang Jin

    2016-02-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels.

  11. Myeloid Deletion of α1AMPK Exacerbates Atherosclerosis in LDL Receptor Knockout (LDLRKO) Mice.

    Science.gov (United States)

    Cao, Qiang; Cui, Xin; Wu, Rui; Zha, Lin; Wang, Xianfeng; Parks, John S; Yu, Liqing; Shi, Hang; Xue, Bingzhong

    2016-06-01

    Macrophage inflammation marks all stages of atherogenesis, and AMPK is a regulator of macrophage inflammation. We therefore generated myeloid α1AMPK knockout (MAKO) mice on the LDL receptor knockout (LDLRKO) background to investigate whether myeloid deletion of α1AMPK exacerbates atherosclerosis. When fed an atherogenic diet, MAKO/LDLRKO mice displayed exacerbated atherosclerosis compared with LDLRKO mice. To determine the underlying pathophysiological pathways, we characterized macrophage inflammation/chemotaxis and lipid/cholesterol metabolism in MAKO/LDLRKO mice. Myeloid deletion of α1AMPK increased macrophage inflammatory gene expression and enhanced macrophage migration and adhesion to endothelial cells. Remarkably, MAKO/LDLRKO mice also displayed higher composition of circulating chemotaxically active Ly-6C(high) monocytes, enhanced atherosclerotic plaque chemokine expression, and monocyte recruitment into plaques, leading to increased atherosclerotic plaque macrophage content and inflammation. MAKO/LDLRKO mice also exhibited higher plasma LDL and VLDL cholesterol content, increased circulating apolipoprotein B (apoB) levels, and higher liver apoB expression. We conclude that macrophage α1AMPK deficiency promotes atherogenesis in LDLRKO mice and is associated with enhanced macrophage inflammation and hypercholesterolemia and that macrophage α1AMPK may serve as a therapeutic target for prevention and treatment of atherosclerosis. PMID:26822081

  12. Targeted disruption of LDLR causes hypercholesterolemia and atherosclerosis in Yucatan miniature pigs.

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    Bryan T Davis

    Full Text Available Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR gene in an effort to provide an improved large animal model of familial hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models because of similarities to humans in physiology, anatomy, genetics, and size. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, male and female LDLR+/- pigs were generated. Subsequent breeding of heterozygotes produced LDLR-/- pigs. When fed a standard swine diet (low fat, no cholesterol, LDLR+/- pigs exhibited a moderate, but consistent increase in total and LDL cholesterol, while LDLR-/- pigs had considerably elevated levels. This severe hypercholesterolemia in homozygote animals resulted in atherosclerotic lesions in the coronary arteries and abdominal aorta that resemble human atherosclerosis. These phenotypes were more severe and developed over a shorter time when fed a diet containing natural sources of fat and cholesterol. LDLR-targeted Yucatan miniature pigs offer several advantages over existing large animal models including size, consistency, availability, and versatility. This new model of cardiovascular disease could be an important resource for developing and testing novel detection and treatment strategies for coronary and aortic atherosclerosis and its complications.

  13. Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits

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    Li-ming Ruan, Wei Cai, Jun-zhu Chen, Jin-feng Duan

    2010-01-01

    Full Text Available Aim: to investigate effects of Losartan on expression of connexin 40 and 43 (Cx40 and Cx43, in arteries at the early stage of atherosclerosis in a rabbit model. Methods: A total of 28 male New Zealand white rabbits were divided into following groups: control group, high fat diet group, and Losartan group (10 mg/kg/day. Losartan was administrated in food for two weeks. Iliac arteries were obtained for immunohistochemistry, transmission electron microscopy, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR. Results: Transmission electron microscopy revealed abundant gap junctions between neointimal smooth muscle cells (SMCs, which were markedly reduced by treatment. RT-PCR and Western blot assay showed that the mRNA and protein expression of Cx40 and Cx43 were elevated in the neointimal area at the early stage of atherosclerosis. The mRNA and protein expression of Cx43 were significantly down-regulated by losartan treatment but those of Cx40 were not markedly changed. Conclusion: Cx40 and Cx43 in the neointimal SMCs were up-regulated at the early stage of atherosclerosis. Losartan (an angiotensin-converting enzyme inhibitor could reduce neointima proliferation and down-regulate the elevated protein expression of Cx43, suggesting the rennin-angiotensin system (RAS plays an important role in the remodeling of gap junction between ventricular myocytes under pathological conditions.

  14. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

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    Heera Ram

    2014-01-01

    Full Text Available Acacia senegal L. (Fabaceae seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil for 15 days. Circulating total cholesterol (TC, HDL-cholesterol (HDL-C, LDL-cholesterol (LDL-C, triglycerides, and VLDL-cholesterol (VLDL-C levels; atherogenic index (AI; cardiac lipid peroxidation (LPO; planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34±0.72 and increased lumen volume (51.65±3.66, administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o. for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.

  15. Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4-NF-κB pathway.

    Science.gov (United States)

    Luo, Hong; Wang, Jing; Qiao, Chenhui; Ma, Ning; Liu, Donghai; Zhang, Weihua

    2015-01-01

    Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and increases in HDL cholesterol levels, indicating a potential antiatherosclerotic effect of PYC through the regulation of lipid levels. Additionally, PYC preconditioning markedly decreased foam cell formation and lipid accumulation in lipopolysaccharide (LPS)-stimulated human THP-1 monocytes. A mechanistic analysis indicated that PYC decreased the lipid-related protein expression of adipose differentiation-related protein (ADRP) and adipocyte lipid-binding protein (ALBP/aP2) in a dose-dependent manner. Further analysis confirmed that PYC attenuated LPS-induced lipid droplet formation via ADRP and ALBP expression through the Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) pathway, because pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-κB (PDTC) strikingly mitigated the LPS-induced increase in ADRP and ALBP. Together, our results provide insight into the ability of PYC to attenuate bacterial infection-triggered pathological processes associated with atherosclerosis. Thus PYC may be a potential lead compound for the future development of antiatherosclerotic CVD therapy. PMID:26492950

  16. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production.

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    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A; Zhou, Zhou; Sun, Lijie; Mathison, Angela J; Garcia-Barrio, Minerva T; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J; Rader, Daniel J; Urrutia, Raul; Chen, Y Eugene

    2015-10-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID:26368306

  17. Protectors or Traitors: The Roles of PON2 and PON3 in Atherosclerosis and Cancer

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    Ines Witte

    2012-01-01

    Full Text Available Cancer and atherosclerosis are major causes of death in western societies. Deregulated cell death is common to both diseases, with significant contribution of inflammatory processes and oxidative stress. These two form a vicious cycle and regulate cell death pathways in either direction. This raises interest in antioxidative systems. The human enzymes paraoxonase-2 (PON2 and PON3 are intracellular enzymes with established antioxidative effects and protective functions against atherosclerosis. Underlying molecular mechanisms, however, remained elusive until recently. Novel findings revealed that both enzymes locate to mitochondrial membranes where they interact with coenzyme Q10 and diminish oxidative stress. As a result, ROS-triggered mitochondrial apoptosis and cell death are reduced. From a cardiovascular standpoint, this is beneficial given that enhanced loss of vascular cells and macrophage death forms the basis for atherosclerotic plaque development. However, the same function has now been shown to raise chemotherapeutic resistance in several cancer cells. Intriguingly, PON2 as well as PON3 are frequently found upregulated in tumor samples. Here we review studies reporting PON2/PON3 deregulations in cancer, summarize most recent findings on their anti-oxidative and antiapoptotic mechanisms, and discuss how this could be used in putative future therapies to target atherosclerosis and cancer.

  18. Association of periodontitis with rheumatoid arthritis and atherosclerosis: Novel paradigms in etiopathogeneses and management?

    Science.gov (United States)

    Soory, Mena

    2010-01-01

    There is increasing documentation of a link between inflammatory periodontal disease affecting the supporting structure of teeth, rheumatoid arthritis, and coronary artery disease. Periodontitis is initiated predominantly by Gram-negative bacteria and progresses as a consequence of the host inflammatory response to periodontal pathogens. Lipopolysaccharide, a cell wall constituent stimulates the production of inflammatory cytokines via the activation of signaling pathways perpetuating inflammatory pathogenesis in a cyclical manner in susceptible individuals; with an element of autoimmune stimulation, not dissimilar to the sequential events seen in RA. Periodontitis, also implicated as a risk factor for cardiovascular disease, promotes mechanisms for atherosclerosis by enhancing an imbalance in systemic inflammatory mediators; more direct mechanisms attributed to microbial products are also implicated in both RA and atherogenesis. Severe periodontal disease characterized by clinical and radiographic parameters has been associated with ischemic stroke risk, significant levels of C-reactive protein and serum amyloid A, amongst others common to both periodontitis and atherosclerosis. Existing data supports the hypothesis that persistent localized infection in periodontitis may influence systemic levels of inflammatory markers and pose a risk for RA and atherosclerosis. A common nucleus of activity in their pathogeneses provides novel paradigms of therapeutic targeting for reciprocal benefit.

  19. Coronary atherosclerosis is already ongoing in pre-diabeticstatus: Insight from intravascular imaging modalities

    Institute of Scientific and Technical Information of China (English)

    Osamu Kurihara; Masamichi Takano; Yoshihiko Seino; Wataru Shimizu; Kyoichi Mizuno

    2015-01-01

    Diabetes mellitus is a powerful risk factor of coronaryartery disease (CAD), leading to death and disability.In recent years, given the accumulating evidence thatprediabetes is also related to increasing risk of CADincluding cardiovascular events, a new guideline hasbeen proposed for the treatment of blood cholesterolfor primary prevention of cardiovascular events. Thisguideline recommends aggressive lipid-lowering statintherapy for primary prevention in diabetes and otherpatients. The ultimate goal of patient managementis to inhibit progression of systemic atherosclerosisand prevent fatal cardiovascular events such as acutecoronary syndrome (ACS). Because disruption ofatherosclerotic coronary plaques is a trigger of ACS,the high-risk atheroma is called a vulnerable plaque.Several types of novel diagnostic imaging technologieshave been developed for identifying the characteristicsof coronary atherosclerosis before the onset of ACS,especially vulnerable plaques. According to coronaryangioscopic evaluation, atherosclerosis severity andplaque vulnerability were more advanced in prediabeticthan in nondiabetic patients and comparable to thatin diabetic patients. In addition, pharmacologicalintervention by statin therapy changed plaque color andcomplexity, and the dynamic changes in plaque featuresare considered plaque stabilization. In this article, wereview the findings of atherosclerosis in prediabetes,detected by intravascular imaging modalities, and thetherapeutic implications.

  20. Spectroscopic studies on the modifications of lipoproteins by human myeloperoxidase - implications for atherosclerosis

    International Nuclear Information System (INIS)

    The mortality as a consequence of atherosclerosis is the major cause of death in the developed world and a wealth of evidence now indicates that low density lipoprotein must be modified in order to promote atherosclerosis. This modification may involve hypochlorous acid, released by the enzyme myeloperoxidase which catalyses the reaction of hydrogen peroxide with chloride ions. It was shown here that hypochlorous acid is produced in micromolar concentrations and is rapidly consumed by low density lipoprotein in a concentration dependent manner. The production of hypochlorous acid by the myeloperoxidase/hydrogen peroxide/chloride-system was accompanied by concomitant alterations of low density lipoprotein as detected by dynamic light scattering, fluorescence of a surface lipid label, native tryptophan fluorescence, liquid chromatography/mass spectrometry of phosphatidylcholines and UV absorption spectroscopy. It was shown that all components of the myeloperoxidase/hydrogen peroxide/chloride-system have rate determining effects on lipoprotein modification. Furthermore the kinetics of the decrease of tryptophan fluorescence was used to compare the effectiveness of MPO inhibitors that block production of hypochlorous acid with compounds that act as hypochlorous acid traps. Summarizing, the results of this study in turn provide important information required for the study of oxidative damage in the pathogenesis of atherosclerosis by myeloperoxidase in vivo. (author)

  1. Sudden death related to advanced coronary atherosclerosis in mini-pigs

    International Nuclear Information System (INIS)

    Advanced coronary atherosclerosis was produced in 30 mini-pigs by a combination of a hypercholesterolaemic diet and X-irradiation to the precordial region. Within 11-25 weeks after the irradiation, 13 of the 30 animals died a sudden death probably caused by coronary atherosclerosis. The contents of free and ester-bound cholesterol in the right coronary artery were significantly higher in the animals which died spontaneously than in surviving animals. In an untreated group of 12 animals 7 died whereas in a group treated with β-pyridylcarbinol only 1 out of 5 died. In the coronary arteries, the contents of both free and ester-bound cholesterol were significantly lower in the β-pyridylcarbinol-treated animals. In a sulfinpyrazontreated group 3 out of 8, and in a metoprolol-treated group 2 out of 5 animals died. None of these drugs reduced the accumulation of cholesterol in the coronary arteries. The rate of sudden death was 26 +- 6% (P<0.05) lower in the combined group of treated animals than in the untreated ones. By regular ECG recordings, signs which could predict the fatal outcome of the experiment were looked for. Although depressed ST segments were present before death in a few animals, this was not a regular phenomenon. It is concluded that advanced coronary atherosclerosis in mini-pigs often leads to sudden death and that this animal model seems suitable for testing the potential therapeutic effects of drugs. (author)

  2. CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis

    Science.gov (United States)

    Silva, Rosemeire A.; Giordano, Ricardo J.; Gutierrez, Paulo S.; Rocha, Viviane Z.; Rudnicki, Martina; Kee, Patrick; Abdalla, Dulcinéia S. P.; Puech-Leão, Pedro; Caramelli, Bruno; Arap, Wadih; Pasqualini, Renata; Meneghetti, José C.; Marques, Fabio L. N.; Khoobchandani, Menka; Katti, Kattesh V.; Lugão, Ademar B.; Kalil, Jorge

    2016-01-01

    The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC) was synthesized and labeled with 111InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases. PMID:27563889

  3. One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Kukreja A

    2014-05-01

    Full Text Available Aastha Kukreja,1 Eun-Kyung Lim,2–4 Byunghoon Kang,1 Yuna Choi,2 Taeksu Lee,1 Jin-Suck Suh,2,3 Yong-Min Huh,2,3 Seungjoo Haam1,31Department of Chemical and Biomolecular Engineering, College of Engineering, 2Department of Radiology, College of Medicine, Yonsei University, Seoul, Republic of Korea; 3YUHS-KRIBB Medical Convergence Research Institute, Seoul, Republic of Korea; 4BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of KoreaAbstract: In this study, dextran-encrusted magnetic nanoclusters (DMNCs were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease.Keywords: magnetic nanocrystal, magnetic resonance imaging, atherosclerosis, macrophages, dextran

  4. MicroRNAs and atherosclerosis%微小RNA与动脉粥样硬化

    Institute of Scientific and Technical Information of China (English)

    化定超; 闫晓光; 郭庚; 鲁晨阳

    2015-01-01

    Atherosclerosis is the most important cause of ischemic stroke. microRNAs can play an important role in the lipid metabolism, vascular inflammatory response, angiogenesis, as wel as smooth muscle cel proliferation and phenotypic conversion, etc. by regulating the functions of vascular endothelial cel s, vascular smooth muscle cel s, and mononuclear macrophages. It is closely associated with the occurrence and development of atherosclerosis. This article mainly reviews the regulatory effect of microRNAs on lipid metabolism and vascular inflammatory response in pathogenesis of atherosclerosis.%动脉粥样硬化是缺血性卒中最主要的病因。微小RNA能通过调控血管内皮细胞、血管平滑肌细胞以及单核巨噬细胞等的功能,在脂质代谢、血管炎性反应、新生血管形成以及平滑肌细胞增生和表型转换等方面发挥重要作用,与动脉粥样硬化的发生和发展密切相关。文章主要就微小RNA对动脉粥样硬化发病机制中脂质代谢和血管炎性反应的调节作用进行综述。

  5. Arachidonate 15-lipoxygenase type B knockdown leads to reduced lipid accumulation and inflammation in atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Lisa U Magnusson

    Full Text Available Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promote local inflammation and is expressed in lipid-loaded macrophages (foam cells present in the atherosclerotic lesions. Here, we investigated the role of ALOX15B in foam cell formation in human primary macrophages and found that silencing of human ALOX15B decreased cellular lipid accumulation as well as proinflammatory cytokine secretion from macrophages. To investigate the role of ALOX15B in promoting the development of atherosclerosis in vivo, we used lentiviral shRNA silencing and bone marrow transplantation to knockdown mouse Alox15b gene expression in LDL-receptor-deficient (Ldlr(-/- mice. Knockdown of mouse Alox15b in vivo decreased plaque lipid content and markers of inflammation. In summary, we have shown that ALOX15B influences progression of atherosclerosis, indicating that this enzyme has an active proatherogenic role.

  6. A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

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    Juan Lin

    2013-01-01

    Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

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

    Science.gov (United States)

    Ma, Xiaojuan; Feng, Yingmei

    2016-01-01

    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. PMID:27447612

  8. Animal model of atherosclerosis using rabbit experimentally induced by combination of X-ray and hypercholesterolemia

    International Nuclear Information System (INIS)

    An attempt was made to prepare an animal model of atherosclerosis similar to human lesions. The experimental animals were male Japanese white rabbits weighting about 2 kg. Hypercholesterolemia was experimentally induced by giving a 1% cholesterol diet. Four weeks later, a single dose of 45 Gy was delivered to the femur to produce vascular changes. Soon after irradiation, immunohistochemical examination revealed the adhesion and invasion of macrophages to endothelial cells, followed by accumulation of foam cells and thickness of the intimal plaques. Three months after irradiation, these thickened plaques became fibrotic, calcified, and necrotic. The tunica media was thinned and the internal elastic lamella was destroyed. Irradiated arteries exhibited not only severe narrowing of the lumen but also aneurysmal dilation and the lesions of the irradiated arteries resembled human atherosclerosis. In conclusion, the atherosclerotic model produced by combining experimental hypercholesterolemia and X-ray irradiaiton may serve as a useful model for studies on atherosclerosis because it can be prepared with no need of complicated or time-consuming procedures. (N.K.)

  9. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

    Science.gov (United States)

    Choe, Hansaem; Hwang, Ji-Yun; Yun, Jin A; Kim, Ji-Myung; Song, Tae-Jin; Chang, Namsoo; Kim, Yong-Jae

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS A total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed. RESULTS When compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P atherosclerosis than in those without. Overall vitamin B12 intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test. CONCLUSIONS When compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke.

  10. Endocan Levels and Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus.

    Science.gov (United States)

    Icli, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Uslu, Ali Ugur; Balta, Sevket; Mikhailidis, Dimitri P; Ozturk, Cengiz; Arslan, Sevket; Sakız, Davut; Sahin, Muhammed; Kucuk, Adem

    2016-09-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. A major cause of morbidity and mortality in SLE is accelerated atherosclerosis. Endothelial-specific molecule 1 (endocan) is a potential predictor of vascular events and is expressed in response to inflammatory cytokines in endothelial cells. We investigated the relationship between endocan and carotid intima-media thickness (cIMT) as a marker of early atherosclerosis. We included 44 women with SLE and 44 healthy women as controls. Disease severity of SLE was evaluated using the SLE Disease Activity Index. Endocan, C-reactive protein, erythrocyte sedimentation rate (ESR), and lipid panel were measured. The cIMT was 0.70 (range: 0.45-1.20) mm in patients with SLE and 0.40 (0.25-0.60) mm in controls (P < .001). Endocan value was 1.6 ± 0.9 ng/mL in controls and 2.2 ± 1.0 ng/mL in patients with SLE (P = .014). Endocan levels were positively correlated with cIMT (r = .469, P < .001), body mass index (r = .373, P = .013), and ESR (r = .393, P = .008). Endocan level may be associated with subclinical atherosclerosis in SLE. Consequently, endocan levels may be a promising clinical tool for patients with SLE as a guide for preventive strategy. PMID:26614790

  11. Determinants of preclinical atherosclerosis are different in type 1 and type 2 diabetic women.

    Science.gov (United States)

    Piťhová, P; Štechová, K; Piťha, J; Lánská, V; Kvapil, M

    2016-06-20

    Diabetes mellitus type 2 ranks among the strongest predictors of cardiovascular diseases (CVD) while the association of type 1 diabetes with CVD is more complex. We studied differences between type 1 and 2 diabetic women regarding association of cardiovascular risk factors with preclinical atherosclerosis expressed as intima-media thickness of common carotid (IMT CCA) and femoral arteries (IMT CFA) measured by high resolution ultrasound. Women with type 1 (n=203) and type 2 diabetes (n=123) were examined with regard to the presence of cardiovascular risk factors. In type 1 diabetic women strong association between IMT CCA and body mass index, waist circumference, and total body fat was found in contrast to type 2 diabetic women. In type 2 diabetic women strong association between IMT CCA and fasting glucose, glycated hemoglobin, and atherogenic index of plasma (log TG/HDL cholesterol) was observed in contrast to type 1 diabetic women. In type 1 diabetic women, IMT CFA was associated with body fat in contrast to type 2 diabetic women. Preclinical atherosclerosis in type 1 diabetic women was strongly associated with factors reflecting body fat and its distribution, while in type 2 diabetic women preclinical atherosclerosis was associated with markers reflecting glucose and lipid metabolic disorders. PMID:26447509

  12. Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis.

    Science.gov (United States)

    Di Pietro, Natalia; Formoso, Gloria; Pandolfi, Assunta

    2016-09-01

    Atherosclerosis is a progressive disease in which endothelial cell dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation, lead to the loss of vascular homeostasis. Oxidized low-density lipoprotein (oxLDL) may play a pre-eminent function in atherosclerotic lesion formation, even if their role is still debated. Several types of scavenger receptors (SRs) such as SR-AI/II, SRBI, CD36, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), toll-like receptors (TLRs) and others can promote the internalization of oxLDL. They are expressed on the surface of vascular wall cells (endothelial cells, macrophages and smooth muscle cells) and they mediate the cellular effects of oxLDL. The key influence of both oxLDL and SRs on the atherogenic process has been established in atherosclerosis-prone animals, in which antioxidant treatment and/or silencing of SRs has been shown to reduce atherogenesis. Despite some discrepancies, the indication from cohort studies that there is an association between oxLDL and cardiovascular (CV) events seems to point toward a role for oxLDL in atherosclerotic plaque progress and disruption. Finally, randomized clinical trials using antioxidants have demonstrated benefits only in high-risk patients, suggesting that additional proofs are still needed to better define the involvement of each type of modified LDL in the development of atherosclerosis. PMID:27256928

  13. Feasibility study on RI biochip Application to detection of risk factors of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kyong Cheol; Choi, Mi Hee; Park, Sang Hyun [Korea Atomic Energy Research Institte, Jeongeup (Korea, Republic of); Cho, Kyung Hyun [Yeungnam University, Gyeongsan (Korea, Republic of); Lee, Ki Teak [Chungnam National University, Daejeon (Korea, Republic of)

    2009-03-15

    Microarrays can be used to screen thousands of binding events in a parallel and high throughput fashion and are of major importance in discase diagnosis and drug discovery. The use of radioisotope is conventionally regarded as one of the most sensitive detection methods. Atherosclerosis is a common disorder affecting arterial blood vessels. It happens when fat, cholesterol, and other substances made in the arterial blood vessels form a hard substances called plaque. Lipoprotein-associated phospholipase A{sub 2} (Lp-PLA{sub 2}), a phospholipase A{sub 2} enzyme, is used as a marker for cardiac disease. The detection of Lp-PLA{sub 2} was accomplished by using radioactive [{sup 3}H-acetyl] PAF as a substrate and a feasibility study on RI biochip application to detection of Lp-PLA{sub 2}, a risk factors of atherosclerosis was performed. Inhibitive activity of a native plant extract was also determined by using the RI biochip. It was found to be applicable to a high-throughput screening of inhibitors for developing atherosclerosis therapeutic agents.

  14. Selective endothelial overexpression of arginase II induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice.

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    Boris L Vaisman

    Full Text Available Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis.Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions.We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.

  15. Low Density Lipoprotein-Containing Circulating Immune Complexes: Role in Atherosclerosis and Diagnostic Value

    Directory of Open Access Journals (Sweden)

    Igor A. Sobenin

    2014-01-01

    Full Text Available It has been suggested that low density lipoprotein-containing circulating immune complexes (LDL-CIC play a role in atherogenesis and are involved in the formation of early atherosclerotic lesion. These complexes, as well as anti-LDL autoantibodies, have been found in the blood and in the atherosclerotic lesions of patients with different cardiovascular diseases, as well as in the blood of animals with experimental atherosclerosis. It can be suggested that the presence of anti-LDL antibodies in the blood is a result of immune response induced by lipoprotein modification. LDL-CIC differs from native LDL in many aspects. It has much lower sialic acid content, smaller diameter, and higher density and is more electronegative than native LDL. Fraction of LDL-CICs is fundamental to the serum atherogenicity manifested at the cellular level. LDL-CIC, unlike native LDL, is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol, in cells cultured from uninvolved human aortic intima and in macrophage cultures. After removal of LDL-CIC, the CHD patient’s sera lose their atherogenic properties. Titer of LDL-CIC in blood serum significantly correlates with progression of atherosclerosis in human in vivo and has the highest diagnostic value among other measured serum lipid parameters. Elevated CIC-cholesterol might well be a possible risk factor of coronary atherosclerosis.

  16. Diagonal ear lobe crease and atherosclerosis: a review of the medical literature and dental implications.

    Science.gov (United States)

    Friedlander, Arthur H; López-López, José; Velasco-Ortega, Eugenio

    2012-01-01

    In Spain a significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodomal symptoms. The diagonal ear lobe crease (DELC) has been characterized in the medical literature as a surrogate marker which can identify high risk patients having occult atherosclerosis. This topic however has not been examined in either the medical or dental literature emanating from Spain. The majority of clinical, angiography and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. A minority of studies have however failed to support this hypothesis. More recently reports using B mode ultrasound have also linked DELC to atherosclerosis of the carotid artery and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. DELC is readily visible during head and neck cancer screening examinations. In conjunction with the patient's medical history, vital signs, and panoramic radiograph, the DELC may assist in atherosclerotic risk.

  17. 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.

  18. Insight into the Spectrum of Coronary Atherosclerosis in Asymptomatic Urban Han Chinese Population by Coronary Computed Tomography Angiography

    Science.gov (United States)

    Li, Jiangbing; Liu, Ruihong; Ji, Xiaokang; Xue, Hao; Zhang, Guang; Wang, Chunxia; Chen, Qicai; Xue, Fuzhong; Cui, Lianqun

    2015-01-01

    Objectives Highlighted the spectrum of coronary atherosclerosis in asymptomatic population by Computed Tomography Angiography (CTA) and developed a surrogation of expensive CTA to early detect coronary atherosclerosis. Methods Three hundred and seven self-referred urban Han Chinese asymptomatic individuals underwent coronary CTA were consecutively enrolled. Total plaque score (TPS), Segment stenosis score (SSS) and Coronary Artery Disease severity (CADS) were used to measure and illustrate the spectrum of atherosclerosis burden by mapping their incidence and proportion onto coronary artery tree. Logistic regression model was further used to explore the association between lipid biomarkers and TPS (SSS) for developing a surrogation of CTA to early detect coronary atherosclerosis. Results We found that the incidence of TPS, SSS and CADS were up to 71.34%, 68.08%, and 71.34%; and high-risk individuals reached up to 11.07%, 15.31% and 16.29% respectively. All TPS, SSS and CADS were much higher in male than female, and have trend of increasing with age. The most lesion segment emerged on proximal LAD, followed by proximal RCA, mid LAD, proximal LCX, and mid RCA with mixed plaque as dominant. HDL-C was a predictor to both TPS [OR: 0.12 (0.02–0.82)] and SSS [OR: 0.15 (0.03–0.76)], and could identify the serious atherosclerosis subjects of TPS or SSS score >5 (AUC 0.73 and 0.70). Conclusions The atherosclerosis plaque burden was about one in ten as high-risk individuals in this specific urban Han Chinese population. As potential surrogation of CTA, HDL-C was recognized as a significant predictor to atherosclerosis burden and revealed a good performance for identifying high-risk individuals. PMID:26151132

  19. Insight into the Spectrum of Coronary Atherosclerosis in Asymptomatic Urban Han Chinese Population by Coronary Computed Tomography Angiography.

    Directory of Open Access Journals (Sweden)

    Jiangbing Li

    Full Text Available Highlighted the spectrum of coronary atherosclerosis in asymptomatic population by Computed Tomography Angiography (CTA and developed a surrogation of expensive CTA to early detect coronary atherosclerosis.Three hundred and seven self-referred urban Han Chinese asymptomatic individuals underwent coronary CTA were consecutively enrolled. Total plaque score (TPS, Segment stenosis score (SSS and Coronary Artery Disease severity (CADS were used to measure and illustrate the spectrum of atherosclerosis burden by mapping their incidence and proportion onto coronary artery tree. Logistic regression model was further used to explore the association between lipid biomarkers and TPS (SSS for developing a surrogation of CTA to early detect coronary atherosclerosis.We found that the incidence of TPS, SSS and CADS were up to 71.34%, 68.08%, and 71.34%; and high-risk individuals reached up to 11.07%, 15.31% and 16.29% respectively. All TPS, SSS and CADS were much higher in male than female, and have trend of increasing with age. The most lesion segment emerged on proximal LAD, followed by proximal RCA, mid LAD, proximal LCX, and mid RCA with mixed plaque as dominant. HDL-C was a predictor to both TPS [OR: 0.12 (0.02-0.82] and SSS [OR: 0.15 (0.03-0.76], and could identify the serious atherosclerosis subjects of TPS or SSS score >5 (AUC 0.73 and 0.70.The atherosclerosis plaque burden was about one in ten as high-risk individuals in this specific urban Han Chinese population. As potential surrogation of CTA, HDL-C was recognized as a significant predictor to atherosclerosis burden and revealed a good performance for identifying high-risk individuals.

  20. 铁代谢与动脉硬化的发生发展%Iron metabolism and atherosclerosis development

    Institute of Scientific and Technical Information of China (English)

    姜榆; 王旗; 乔彤

    2015-01-01

    Iron is an essential mineral in many proteins andenzymes in human physiology and is involved in various inflammation disease like atherosclerosis. Atherosclerosis is a chronic systemic inflammation disease. In atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals that contribute to lipid modification, which is essential to atheroma formation. Inflammation further fuels iron-related pathologic processes associated with plaque progression. Although iron is very important in atherosclerosis development, the detailed mechanism of iron obstruction in atherosclerosis plaque is unclear. This review summarizes the role of iron in atherosclerosis with considerable implications for novel diagnostic and therapeutic approaches.%铁元素是多种蛋白及酶的辅助元素。动脉硬化(atherosclerosis, AS)是一种全身性慢性炎症性血管疾病。铁可以导致巨噬细胞中ROS产生增多,且会促进脂质过氧化,最终促进动脉粥样硬化的进展并降低斑块的稳定性。尽管铁在动脉粥样硬化中的作用已经比较清楚,但关于斑块处铁代谢紊乱的机制仍未清楚,本文对铁代谢与动脉硬化的相关性进行综述,旨在了解并阐述炎症、肥胖等动脉硬化的危险因素和铁代谢之间的关系,从而对动脉硬化的诊断及治疗有一定的启发。

  1. Individual with subclinical atherosclerosis have impaired proliferation of blood outgrowth endothelial cells, which can be restored by statin therapy.

    Directory of Open Access Journals (Sweden)

    Javier Martin-Ramirez

    Full Text Available BACKGROUND: To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD, we cultured blood outgrowth endothelial cells (BOECs of patients with premature CAD and their first degree relatives (FDR. Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. METHODS AND RESULTS: Patients with premature CAD (men 0. We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96. Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. CONCLUSION: BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.

  2. Berberine promotes the development of atherosclerosis and foam cell formation by inducing scavenger receptor A expression in macrophage

    Institute of Scientific and Technical Information of China (English)

    Ke Li; Wenqi Yao; Xiudan Zheng; Kan Liao

    2009-01-01

    Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins (LDL) receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice was investigated, in apoE-/-mice, berberine induced in vivo foam cell formation and promoted atherosclerosis development. The foam cell for-mation induced by berberine was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A (SR-A) expression in macrophages, berberine increased the uptake of modified LDL (DiO-Ac-LDL). Berberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A ex-pression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the cells involved in ath-erosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.

  3. Site-specific influence of polyunsaturated fatty acids on atherosclerosis in immune incompetent LDL receptor deficient mice.

    Science.gov (United States)

    Reardon, Catherine A; Blachowicz, Lydia; Gupta, Gaorav; Lukens, John; Nissenbaum, Michael; Getz, Godfrey S

    2006-08-01

    Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels, atherosclerosis, and the immune system. In this study, we fed male LDL receptor deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to determine if the response to diet was influenced by immune status. Relative to milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-) RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary effect of PUFA on plasma lipids was not due to its inhibition of the immune system. Neither diet nor immune status influenced hepatic triglyceride production and post-heparin lipase activity, suggesting that the differences in triglyceride levels are due to differences in rates of catabolism of triglyceride-rich lipoproteins. While both diets promoted atherogenesis, both aortic root and innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed animals. In contrast, a site-specific effect of PUFA was observed in the immune incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but not innominate artery atherosclerosis, was less in PUFA fed animal. These results suggest that PUFA and the immune system may influence innominate artery atherosclerosis by some overlapping mechanisms.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R;

    2011-01-01

    Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening...... for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score≥400, carotid intima...

  6. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R;

    2011-01-01

    Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening...... for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

  7. Selected atherosclerosis risk factors in youth aged 13–15 years 

    Directory of Open Access Journals (Sweden)

    Agnieszka Michalska

    2012-09-01

    Full Text Available Introduction:The high frequency of cases of circulatory system conditions in Europe and other countries around the world requires scientific research to define risk factors of early atherosclerotic changes. The aim of the present study was to define which students are at danger of developing atherosclerosis by means of measuring cholesterol and triglyceride levels in blood as well as defining the correlation between atherosclerosis risk factors and arterial blood pressure, physical fitness and efficiency of the subjects.Material/Methods:The research covered 167 students of Public Junior High School ¹1 in Biala Podlaska aged 13–15 years. Accutrend GCT was employed to define the levels of total cholesterol and triglycerides in the screen test. Those students who were found to have increased values of biochemical parameters of capillary blood were subjected to additional blood tests aiming to define complete lipid profile of venous blood. The blood pressure in subjects was tested three times. The Moderate-to-Vigorous Physical Activity (MVPA test, suggested by American authors, was employed to define physical activity in subjects. EUROFIT was employed to define physical efficiency.Results:Among the 167 subjects there were found 42 students (25.1�20whose lipid level in capillary blood proved to be increased. Full lipid profile tests proved that 16 students (9.6�20had increased blood lipid levels; those subjects constituted the risk group. Subjects in the risk group were characterized by lower levels of physical activity and physical efficiency compared to subjects with normal blood lipid level. Moreover, the frequency of hypertension was greater in risk group subjects compared to subjects with normal blood lipid levels.Inferences:Students diagnosed with atherosclerosis risk factors require observation and early prophylactics by adopting habits of healthy physical activity.

  8. Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices

    Directory of Open Access Journals (Sweden)

    F.M. Perrotta

    2013-07-01

    Full Text Available The aim of the study was to evaluate atherosclerosis in ankylosing spondylitis (AS through the assessment of morphological and functional measures of subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range 43.5/28-69 years; disease duration (median/range 9.7/1-36 years] with AS classified according to modified New York criteria and twenty age and sex related healthy controls with negative past medical history for cardiovascular events were enrolled in the study. In all patients and controls, the intima-media thickness (IMT of common carotid artery, carotid bulb and internal carotid artery, and the flow-mediated dilatation (FMD of non-dominant arm brachial artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy. Furthermore, we assess the main disease activity and disability indices [bath ankylosing spondylitis disease activity index, ankylosing spondylitis disease activity score-eritrosedimentation rate (ASDAS-ESR, ASDAS-C-reactive protein (CRP, bath ankylosing spondylitis metrology index, bath ankylosing spondylitis functional index and acute phase reactants. Plasmatic values of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and homocysteine were carried out in all twenty patients. IMT at carotid bulb was significant higher in patients than in controls (0.67 mm vs 0.54 mm; P=0.03. FMD did not statistically differ between patients and controls (12.5% vs 15%; P>0.05. We found a correlation between IMT at carotid bulb and ESR (rho 0.43; P=0.04. No correlation was found between FMD and disease activity and disability indices. This study showed that in AS patients, without risk factors for cardiovascular disease, carotid bulb IMT, morphological index of subclinical atherosclerosis, is higher than in controls.

  9. Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

    Science.gov (United States)

    Martin, Praxedis; Palmer, Gaby; Rodriguez, Emiliana; Woldt, Estelle; Mean, Isabelle; James, Richard W.; Smith, Dirk E.; Kwak, Brenda R.

    2015-01-01

    Abstract Interleukin (IL)‐33 is a cytokine of the IL‐1 family, which signals through the ST2 receptor. Previous work demonstrated that the systemic administration of recombinant IL‐33 reduces the development of atherosclerosis in apolipoprotein E‐deficient (ApoE−/−) mice by inducing a Th1‐to‐Th2 shift. The objective of our study was to examine the role of endogenous IL‐33 and ST2 in atherosclerosis. ApoE−/−, IL‐33−/−ApoE−/−, and ST2−/−ApoE−/− mice were fed with a cholesterol‐rich diet for 10 weeks. Additionally, a group of ApoE−/− mice was injected with a neutralizing anti‐ST2 or an isotype control antibody during the period of the cholesterol‐rich diet. Atherosclerotic lesion development was measured by Oil Red O staining in the thoracic‐abdominal aorta and the aortic sinus. There were no significant differences in the lipid‐staining area of IL‐33−/−ApoE−/−, ST2−/−ApoE−/−, or anti‐ST2 antibody‐treated ApoE−/− mice, compared to ApoE−/− controls. The absence of IL‐33 signaling had no major and consistent impact on the Th1/Th2 cytokine responses in the supernatant of in vitro‐stimulated lymph node cells. In summary, deficiency of the endogenously produced IL‐33 and its receptor ST2 does not impact the development of atherosclerosis in ApoE‐deficient mice.

  10. Heart-Carotid Pulse Wave Velocity a Useful Index of Atherosclerosis in Chinese Hypertensive Patients.

    Science.gov (United States)

    Li, Chunyue; Xiong, Huahua; Pirbhulal, Sandeep; Wu, Dan; Li, Zhenzhou; Huang, Wenhua; Zhang, Heye; Wu, Wanqing

    2015-12-01

    This study was designed to investigate the relationship between heart-carotid pulse wave velocity (hcPWV) and carotid intima-media thickness (CIMT) in hypertensive patients, and also to examine the effect of pre-ejection period (PEP) on it. Doppler ultrasound device was used to measure CIMT in left common carotid artery. Hypertensive patients were divided into normal (n = 36, CIMT ≤0.8 mm) and thickened (n = 31, CIMT > 0.8 mm) group. Electrocardiogram R-wave-based carotid pulse wave velocity (rcPWV) and aortic valve-carotid pulse wave velocity (acPWV) were calculated as the ratio of the travel length to the pulse transit time with or without PEP, respectively. CIMT has significant relations with rcPWV (r = 0.611, P < 0.0001) and acPWV (r = 0.384, P = 0.033) in thickened group. Moreover, CIMT showed stronger correlation with rcPWV than with acPWV in thickened group. Furthermore, both acPWV and rcPWV were determinant factors of CIMT in thickened group, independent of clinical confounders including age, gender, smoking behavior, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, antihypertensive medication, and plaque occurrence. However, similar results were not found in normal group. Since CIMT has been considered as an index of atherosclerosis, our results suggested that both rcPWV and acPWV could be useful indexes of atherosclerosis in thickened CIMT hypertensive patients. Additionally, if hcPWV is computed with heart-carotid pulse transit time, including PEP could improve the accuracy of atherosclerosis assessment in hypertensive patients. PMID:26705228

  11. Receptor for Advanced Glycation End Products (RAGE) Deficiency Attenuates the Development of Atherosclerosis in Diabetes

    Science.gov (United States)

    Soro-Paavonen, Aino; Watson, Anna M.D.; Li, Jiaze; Paavonen, Karri; Koitka, Audrey; Calkin, Anna C.; Barit, David; Coughlan, Melinda T.; Drew, Brian G.; Lancaster, Graeme I.; Thomas, Merlin; Forbes, Josephine M.; Nawroth, Peter P.; Bierhaus, Angelika; Cooper, Mark E.; Jandeleit-Dahm, Karin A.

    2008-01-01

    OBJECTIVE—Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE−/− model of accelerated atherosclerosis. RESEARCH DESIGN AND METHODS—ApoE−/− and RAGE−/−/apoE−/− double knockout mice were rendered diabetic with streptozotocin and followed for 20 weeks, at which time plaque accumulation was assessed by en face analysis. RESULTS—Although diabetic apoE−/− mice showed increased plaque accumulation (14.9 ± 1.7%), diabetic RAGE−/−/apoE−/− mice had significantly reduced atherosclerotic plaque area (4.9 ± 0.4%) to levels not significantly different from control apoE−/− mice (4.3 ± 0.4%). These beneficial effects on the vasculature were associated with attenuation of leukocyte recruitment; decreased expression of proinflammatory mediators, including the nuclear factor-κB subunit p65, VCAM-1, and MCP-1; and reduced oxidative stress, as reflected by staining for nitrotyrosine and reduced expression of various NADPH oxidase subunits, gp91phox, p47phox, and rac-1. Both RAGE and RAGE ligands, including S100A8/A9, high mobility group box 1 (HMGB1), and the advanced glycation end product (AGE) carboxymethyllysine were increased in plaques from diabetic apoE−/− mice. Furthermore, the accumulation of AGEs and other ligands to RAGE was reduced in diabetic RAGE−/−/apoE−/− mice. CONCLUSIONS—This study provides evidence for RAGE playing a central role in the development of accelerated atherosclerosis associated with diabetes. These findings emphasize the potential utility of strategies targeting RAGE activation in the prevention and treatment of diabetic macrovascular complications. PMID:18511846

  12. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

    Science.gov (United States)

    Choe, Hansaem; Hwang, Ji-Yun; Yun, Jin A; Kim, Ji-Myung; Song, Tae-Jin; Chang, Namsoo; Kim, Yong-Jae

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS A total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed. RESULTS When compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P < 0.001), vegetables (221.1 ± 209.0 g vs. 561.7 ± 306.6 g, P < 0.001), and antioxidants, including vitamins C, E, B6, β-carotene, and folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely associated with the risk of ischemic stroke after adjusting for confounding factors. Intakes of vegetables, vitamins C, B6, B12, and folate per 1,000 kcal were lower in ischemic stroke with cerebral atherosclerosis than in those without. Overall vitamin B12 intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test. CONCLUSIONS When compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke.

  13. Levels of soluble adhesion molecules in patients with various clinical presentations of coronary atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    LU Hui-he; SHENG Zheng-qiang; WANG Yi; ZHANG Li

    2010-01-01

    Background Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was to compare concentrations of soluble forms of adhesion molecules in patients with different clinical presentations of coronary artery disease (CAD).Methods One hundred and twenty-eight patients with CAD were divided into three groups; the first group was acute myocardial infarction group (AMI group, n=45), the second group was unstable angina pectoris group (UAP group, n=48),the third group was stable angina pectoris group (SAP group, n=35). We compared them with patients with normal coronary arteries (control group, n=31). The serum levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were measured in all subjects.Results The serum level of VCAM-1 in the AMI group was significantly higher than in the UAP, SAP and control groups (P <0.01). The level in the UAP group was significantly higher than the SAP group and control group (P <0.01) and the level in the SAP group was significantly higher than in the control group (P <0.01). The serum ICAM-1 level was significantly elevated in the AMI, UAP and SAP groups as compared to the control group (P <0.01). The levels of serum E-selectin and P-selectin in the AMI and UAP groups were significantly higher than in the SAP and control groups (P<0.01).Conclusions Increased levels of VCAM-1 and ICAM-1, E-selectin and P-selectin, as markers of inflammation, showed the importance of inflammatory processes in the development of atherosclerosis and clinical expression of CAD. Soluble ICAM-1, VCAM-1, E-selectin and P-selectin concentrations are useful indicators of the presence of atherosclerosis and the severity of CAD clinical presentation.

  14. The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics

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    Parapid Biljana

    2010-01-01

    Full Text Available Introduction. The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective. The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. Methods. The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (G0, insulin (I0 and lipid panel measurements (TC, HDL, LDL, TG were taken after a 12-hour fasting. Results. The protocol encompassed 40 patients (19 men and 21 women treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis, Group B (18 patients, 45%, with a single-vessel disease and Group C (16 patients, 40%, with multi-vessel disease. Presence of lower insulin sensitivity, higher I0 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F=4.279, p=0.023, A vs. C p=0.012, B vs. C p=0.038; I0: F=3.461 p=0.042, A vs. B p=0.045, A vs. C p=0.013; TC: F=2.572, p=0.09, while no significant difference was found for G0, LDL, HDL and TG. Conclusion. Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

  15. Inhibition of endoplasmic reticulum stress and atherosclerosis by 2-aminopurine in apolipoprotein e-deficient mice.

    Science.gov (United States)

    Zhou, Lichun; Yang, Dezhi; Wu, Dong Fang; Guo, Zhong Mao; Okoro, Emmanuel; Yang, Hong

    2013-01-01

    We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE (-/-) ) mice, so called E(-)/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E(-)/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in apoE (-/-) mice. Our results showed that the level of food intake, bodyweight, plasma cholesterol, and triglycerides was comparable in apoE (-/-) mice treated with or without 2-AP. However, the mean size of atherosclerotic lesions in the aorta sinus as well as the surface area of the entire aorta of 2-AP-treated apoE (-/-) mice were reduced by about 55% and 39%, respectively, compared to samples from untreated control apoE (-/-) mice. In addition, the 2-AP-treated apoE (-/-) mice showed a significant decrease in glucose-regulated protein 78 (GRP78) and phosphorylated eIF-2 α in their aortic samples as compared to levels in untreated control apoE (-/-) mice. These observations suggest that endoplasmic reticulum stress is a causal mechanism for the development of atherosclerosis in apoE (-/-) mice and that therapeutic strategies can be developed for using eIF-2 α phosphorylation inhibitors, such as 2-AP, to prevent or treat atherosclerosis. PMID:23984090

  16. Normal-weight obesity is associated with increased risk of subclinical atherosclerosis

    OpenAIRE

    Kim, Sohee; Kyung, Chanhee; Park, Jong Suk; Lee, Seung-Pyo; Kim, Hye Kyoung; Ahn, Chul Woo; Kim, Kyung Rae; Kang, Shinae

    2015-01-01

    Background Subjects with normal body mass index (BMI) but elevated amounts of body fat (normal-weight obesity; NWO) show cardiometabolic dysregulation compared to subjects with normal BMI and normal amounts of body fat (normal-weight lean; NWL). In this study, we aimed to evaluate whether NWO individuals have higher rates of subclinical atherosclerosis compared to NWL subjects. Methods From a large-scale health checkup system, we identified 2078 normal weight (18.5 ≤ BMI 1 mm2 within and/or a...

  17. IGF-1 Has Plaque-Stabilizing Effects in Atherosclerosis by Altering Vascular Smooth Muscle Cell Phenotype

    OpenAIRE

    von der Thüsen, Jan H; Borensztajn, Keren S.; Moimas, Silvia; van Heiningen, Sandra; Teeling, Peter; Van Berkel, Theo J. C.; Biessen, Erik A. L.

    2011-01-01

    Insulin-like growth factor-1 (IGF-1) signaling is important for the maintenance of plaque stability in atherosclerosis due to its effects on vascular smooth muscle cell (vSMC) phenotype. To investigate this hypothesis, we studied the effects of the highly inflammatory milieu of the atherosclerotic plaque on IGF-1 signaling and stability-related phenotypic parameters of murine vSMCs in vitro, and the effects of IGF-1 supplementation on plaque phenotype in an atherosclerotic mouse model. M1-pol...

  18. 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

  19. Correlation of arterial stiffness index with carotid atherosclerosis in patients with primary hypertension

    Institute of Scientific and Technical Information of China (English)

    Wen-Hua Cai; Li-Min Li; Xue-Min Wang; Cui-Qing Sun; Hai-Wei Zhao; Hui Wang; Rui-Chao Liu

    2016-01-01

    Objective:To explore the correlation of arterial stiffness index with carotid atherosclerosis in patients with primary hypertension.Methods:A total of 86 patients with primary hypertension who were admitted in our hospital from January, 2013 to September, 2015 were included in the study, and divided into the carotid atherosclerosis group (IMT≥0.9 mm, with plaque being detected) and the pure hypertension group (normal IMT) according to the carotid artery color Doppler ultrasound results. According to the ambulatory blood pressure monitoring results, the carotid atherosclerosis group was divided into the low BPV (7.02-9.57) group and the high BPV (>9.57-14.29) group. The non-invasive ambulatory blood pressure monitoring apparatus was used for 24 h blood pressure monitoring, measuring time in the daytime: 6:00-21:59, measuring one time every 30 min; measuring time in the nighttime: 22:00-5:59, measuring one time every 60 min. The dSBP, dDBP, nSBP, nDBP, 24 h SBP, and 24 h DBP were recorded. BPV was expressed as 24 h SCV and 24 h DCV.Results:The dSBP, nSBP, 24 h SBP, 24 h DBP, and 24 h SCV in the carotid atherosclerosis group were significantly higher than those in the pure hypertension group, while the comparison of dDBP, nDBP, and 24 h DCV between the two groups was not statistically significant. The common carotid artery and external carotid artery IMT, and the mean IMT in the high BPV group were significantly higher than those in the low BPV group, and the number of carotid plaques being detected was significantly greater than that in the low BPV group.Conclusions:BPV is involved in the arterial functional and structural changes, resulting in the target organ damage. Detection of carotid IMT is of great significance in evaluating the early vascular damage and predicting the cardiovascular events; therefore, BPV monitoring should be strengthened during the diagnosis and treatment of hypertension.

  20. Increased systemic and local interleukin 9 levels in patients with carotid and coronary atherosclerosis.

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    Ida Gregersen

    Full Text Available OBJECTIVE: Atherosclerosis is a chronic inflammatory disorder that involves a range of inflammatory mediators. Although interleukin (IL-9 has been related to inflammation, there are at present no data on its role in atherosclerosis. Here we have examined IL-9 and IL-9 receptor (IL-9R systemically and locally in patients with coronary and carotid atherosclerosis. METHODS: Plasma IL-9 was quantified by enzyme immunoassay and multiplex technology. IL-9 and IL-9R mRNA were quantified by real-time RT-PCR, and their localization within the lesion was assessed by immunohistochemistry. RESULTS: THE MAIN FINDINGS WERE: (i Patients with carotid atherosclerosis had significantly raised IL-9 plasma levels compared with healthy controls (n = 28, with no differences between asymptomatic (n = 56 and symptomatic (n = 88 patients. (ii On admission, patients with acute ST-elevation myocardial infarction (STEMI (n = 42 had markedly raised IL-9 plasma levels which gradually declined during the first week post-MI. (iii T cells and monocytes from patients with unstable angina (n = 17 had increased mRNA levels of IL-9 as compared with controls (n = 11. (iv Carotid plaques (n = 68 showed increased mRNA levels of IL-9 and IL-9R compared to non-atherosclerotic vessels (n = 10. Co-localization to T cells (IL-9 and IL-9R and macrophages (IL-9 were shown by immunohistochemistry. (v IL-9 increased IL-17 release in peripheral blood mononuclear cells from patients with unstable angina (n = 5 and healthy controls (n = 5 with a particularly enhancing effect in cells from the patient group. CONCLUSION: Our findings show increased IL-9 levels in different atherosclerotic disorders both systemically and within the lesion, suggesting a role for the IL-9/IL-9R axis in the atherosclerotic process, potentially involving IL-17 mediated mechanisms. However, the functional consequences of these findings should be further investigated.

  1. M1- and M2-type macrophage responses are predictive of adverse outcomes in human atherosclerosis

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    Monica De Gaetano

    2016-07-01

    Full Text Available Atherosclerosis is an inflammatory disease caused by endothelial injury, lipid deposition and oxidative stress. This progressive disease can be converted into an acute clinical event by plaque rupture and thrombosis. In the context of atherosclerosis, the underlying cause of myocardial infarction and stroke, macrophages uniquely possess a dual functionality, regulating lipid accumulation and metabolism and sustaining the chronic inflammatory response, two of the most well documented pathways associated with the pathogenesis of the disease. Macrophages are heterogeneous cell populations and it is hypothesized that, during the pathogenesis of atherosclerosis, macrophages in the developing plaque can switch from a pro-inflammatory (MΦ1 to an anti-inflammatory (MΦ2 phenotype and vice versa, depending on the microenvironment. The aim of this study was to identify changes in macrophage subpopulations in the progression of human atherosclerotic disease. Established atherosclerotic plaques from symptomatic and asymptomatic patients with existing coronary artery disease undergoing carotid endarterectomy were recruited to the study. Comprehensive histological and immunohistochemical analyses were performed to quantify the cellular content and macrophage subsets of atherosclerotic lesion. In parallel, expression of MΦ1 and MΦ2 macrophage markers were analysed by real time-PCR and Western blot analysis.Gross analysis and histological staining demonstrated that symptomatic plaques presented greater haemorrhagic activity and the internal carotid was the most diseased segment, based on the predominant prevalence of fibrotic and necrotic tissue, calcifications and haemorrhagic events. Immunohistochemical analysis showed that both MΦ1 and MΦ2 macrophages are present in human plaques. However, MΦ2 macrophages are localised to more stable locations within the lesion. Importantly, gene and protein expression analysis of MΦ1/ MΦ2 markers evidenced that MΦ1

  2. Role of gut microbiota in the modulation of atherosclerosis-associated immune response

    Directory of Open Access Journals (Sweden)

    Dimitry A Chistiakov

    2015-06-01

    Full Text Available Inflammation and metabolic abnormalities are linked to each other. At present, pathogenic inflammatory response was recognized as a major player in metabolic diseases. In humans, intestinal microflora could significantly influence the development of metabolic diseases including atherosclerosis. Commensal bacteria were shown to activate inflammatory pathways through altering lipid metabolism in adipocytes, macrophages, and vascular cells, inducing insulin resistance, and producing trimethylamine-N-oxide. However, gut microbiota could also play the atheroprotective role associated with anthocyanin metabolism and administration of probiotics and their components. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis.

  3. Subclinical atherosclerosis in patients with psoriatic arthritis: a case-control study. Preliminary data

    Directory of Open Access Journals (Sweden)

    M. Zanon

    2011-06-01

    Full Text Available Objective: The aim of this study was to evaluate the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA, correlated with some traditional risk factors of atherosclerosis and with PsA-related disease factors. Methods: Forty-one patients and 41 healthy subjects were evaluated for intima-media thickness (IMT and flow-mediated dilation (FMD, using carotid duplex scanning. IMT values were expressed like IMT mean (cumulative mean of all the IMT mean and M-MAX (cumulative mean of all the higher IMT. Subclinical atherosclerosis markers were correlated with age, body mass index (BMI and blood pressure in both groups, with duration of arthritis, duration of psoriasis, tender and swollen joints, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index, BASFI (Bath Ankylosing Spondylitis Functional Index, erythrocyte sedimentation rate (ESR and C-reactive protein (CRP in patients. Results: IMT mean and M-MAX were both higher in PsA patients compared with controls (0.7±0.15 vs 0.62±0.09 mm; p<0.01 and 0.86±0.21 vs. 0.74±0.13 mm; p<0.01 respectively. FMD was smaller in patients than in controls (5.9±2 vs 7.5±2.8%; p<0.01. Univariate analysis showed a correlation between IMT mean and SBP (r=0.217; p=0.05 and a correlation between M-MAX and age (r=0.392; p<0.001, BMI (r=0.252; p<0.05, SBP (r=0.446; p<0.001 in both groups. In PsA patients M-MAX resulted correlated with ESR (r=0.338; p<0.05 and BASDAI (r=0.322; p<0.05. Conclusions: PsA patients exhibited endothelial dysfunctions which is an early marker of subclinical atherosclerosis, as well as an higher IMT. An interesting correlation between M-MAX and PsA activity index (ESR and BASDAI was found.

  4. Unraveling the environmental and genetic interactions in atherosclerosis: Central role of the gut microbiota.

    Science.gov (United States)

    Org, Elin; Mehrabian, Margarete; Lusis, Aldons J

    2015-08-01

    Recent studies have convincingly linked gut microbiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gut microbiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gut microbiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD.

  5. Establishment of a uremic apolipoprotein E knockout mouse model to explore the mechanism of uremic atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To establish a uremic apoE-/-mouse model to observe serum biochemical parameters and features of aortic root atherosclerosis (AS) in the model. Methods A uremic model was induced surgically in apoE-/- mice:electrocautery of the right kidney at 8 weeks of age and nephrectomy (NX) of the left one 2 weeks later. Control mice were sham-operated. Two weeks after NX,renal functions were detected in the uremic and control mice to evaluate the efficiency of the model. After 10 weeks of NX,blood samples we...

  6. Association of serum sodium concentration with coronary atherosclerosis in China: follow-up study

    Institute of Scientific and Technical Information of China (English)

    En-zhi JIA; Zhen-xia XU; Zhi-jian YANG; Tie-bing ZHU; Lian-sheng WANG; Bo CHEN; Ke-jiang CAO; Jun HUANG; Wen-zhu MA; Xiang LU

    2009-01-01

    Aim: The aim of this study was to test the hypothesis that lower serum sodium may be associated with increased cardiovascular events and all-cause mortality by means of long-term foUow-up of subjects with coronary atherosclerosis in a prospecfive, hospital-based epidemiological study in China. Methods: A prospective, hospital-based epidemiological design was used. The study population consisted of 1069 consecutive patients who were scheduled to undergo coronary angiography for suspected or known coronary atherosclerosis. The severity of coronary atherosclerosis was defined using Gensini's score system. Age, sex-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the quartiles of serum sodium concentration were estimated with Cox proportional hazard models, using quartile 1 as the reference. Cox proportional hazard models were also constructed to estimate the hazard ratios and 95% confidence intervals for all-cause mortality and final end-point events by serum sodium quartile and to adjust for potentially confounding variables. Multivariate models were adjusted for the following variables: age, sex, smoking status, alcohol consumption, body mass index, blood pressure, potassium, chloride, total cholesterol triglycerides, fasting blood glucose, urea, creatinine, uric acid, and Gensini's score.Results: During the median 2.86 years (3011.66 person-years) of follow-up, 176 final end-point events were documented.These events included 79 deaths and 97 readmissions for coronary heart disease. There was a statistically significant inverse association of serum sodium with all-cause mortality (P<0.001). After full adjustment comparing the highest serum sodium quartile to the lowest, there was a non-significant inverse association with aU-cause mortality, with an adjusted hazard ratio (95% CI) of 0.67 (0.25-1.80). After adjustment for age and sex, the hazard ratio and 95% CI for final end-point events across increasing quartiles of serum sodium concentration were

  7. Aortic arch and intra-/extracranial cerebral arterial atherosclerosis in patients suffering acute ischemic strokes

    Institute of Scientific and Technical Information of China (English)

    郭毅; 姜昕; 陈实; 张少文; 赵宏文; 吴瑛

    2003-01-01

    Objective To determine the distribution of aortic arch and intra/extracranial cerebral arterial atherosclerosis in Chinese patients who had suffered acute ischemic strokes. Methods Eighty-nine patients with acute ischemic strokes were included in this study. Transesophageal echocardiography (TEE) was used to evaluate potential sources of embolisms in the aortic arch and in the heart; duplex ultrasound was used for the carotid artery; and intracranial Doppler (TCD) imaging was used for the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and basilar artery (BA). An atherosclerotic lesion in the aortic arch was defined as normal (0); mild plaque (1); moderate plaque (2); and protruding plaque or mobile plaque (3). A lesion in the carotid artery was considered a plaque if the maximal carotid plaque thickness was 1.2 mm. TCD results were deemed abnormal if flow velocity was either greater or lower than normal, and, in the case of the MCA, if an asymmetry index above 21% was measured. Results Of the 89 patients, 52 (58.43%) patients showed evidence of aortic arch atherosclerosis (AAA), including 11 (12.36%) patients graded mild, 18 (20.22%) patients graded moderate, and 23 (25.84%) patients graded severe. Of the 23 patients with severe AAA, AAA was determined to be an important potential embolic source in 14 patients. Forty-nine (50.56%) patients had carotid arterial plaques (CAPs). The incidence of carotid plaques was higher among patients with AAA than among patients without AAA (71.15% vs 21.62%, OR=3.291, 95% CI=1.740-6.225, P<0.001). TCD abnormalities affecting the MCA were found in 54 (60.67%) patients. Differences in incidence of TCD abnormalities between patients with AAA and without AAA (69.23% vs 48.65%) were not significant (OR=1.423, 95% CI=0.976-2.076, P=0.05). There was a higher incidence of AAA in older, male patients with a history of diabetes and smoking. Conclusions AAA is an important potential source of

  8. Triptolide inhibits the progression of atherosclerosis in apolipoprotein E−/− mice

    Science.gov (United States)

    Luo, Longfeng; Yang, Tianlun

    2016-01-01

    Atherosclerosis, the major cause of cardiovascular disease, is accompanied by a chronic inflammatory response during the disease. Triptolide (TPL) is an active natural compound that has been demonstrated to possess anti-inflammatory activities in various cell types. However, the effects of TPL on atherosclerosis have not yet been studied. The goal of the present study was to determine the effects of TPL on apolipoprotein E knock-out (ApoE−/−) mice fed with a high-fat diet and to analyze the changes in lipid metabolism and inflammatory cytokines to clarify the underlying molecular mechanisms. Firstly, the genotypes of ApoE−/− mice and corresponding wild-type mice were identified using polymerase chain reaction. The ApoE−/− mice were randomly divided into four groups: ApoE−/− model mice, and ApoE−/− mice treated with 25, 50 or 100 µg/kg TPL every twice day. Wild-type mice with the same genetic background constituted the fifth group. The mice in each group were given a high-fat diet from week 8 after birth until week 20. Total cholesterol and total triglyceride levels were determined at 16 and 20 weeks. The results demonstrated that the levels of total cholesterol and total triglyceride in the plasma were highly increased in ApoE−/− mice models, compared with those of wild-type mice, and the ApoE−/− mice treated with TPL had decreased levels of total cholesterol and total triglyceride in plasma, which exhibited a dose-dependent reduction as the dose of TPL increased. Moreover, the effects of TPL on the production of inflammatory cytokines in macrophages were determined by ELISA. The results demonstrated that the macrophages from ApoE−/− mice produced high levels of the inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. However, following treatment with TPL doses of 25, 50 and 100 µg/kg, the cytokine levels were significantly decreased in a dose-dependent manner. Additionally, proteins associated with

  9. Graphical modeling of gene expression in monocytes suggests molecular mechanisms explaining increased atherosclerosis in smokers.

    Directory of Open Access Journals (Sweden)

    Ricardo A Verdugo

    Full Text Available Smoking is a risk factor for atherosclerosis with reported widespread effects on gene expression in circulating blood cells. We hypothesized that a molecular signature mediating the relation between smoking and atherosclerosis may be found in the transcriptome of circulating monocytes. Genome-wide expression profiles and counts of atherosclerotic plaques in carotid arteries were collected in 248 smokers and 688 non-smokers from the general population. Patterns of co-expressed genes were identified by Independent Component Analysis (ICA and network structure of the pattern-specific gene modules was inferred by the PC-algorithm. A likelihood-based causality test was implemented to select patterns that fit models containing a path "smoking→gene expression→plaques". Robustness of the causal inference was assessed by bootstrapping. At a FDR ≤0.10, 3,368 genes were associated to smoking or plaques, of which 93% were associated to smoking only. SASH1 showed the strongest association to smoking and PPARG the strongest association to plaques. Twenty-nine gene patterns were identified by ICA. Modules containing SASH1 and PPARG did not show evidence for the "smoking→gene expression→plaques" causality model. Conversely, three modules had good support for causal effects and exhibited a network topology consistent with gene expression mediating the relation between smoking and plaques. The network with the strongest support for causal effects was connected to plaques through SLC39A8, a gene with known association to HDL-cholesterol and cellular uptake of cadmium from tobacco, while smoking was directly connected to GAS6, a gene reported to have anti-inflammatory effects in atherosclerosis and to be up-regulated in the placenta of women smoking during pregnancy. Our analysis of the transcriptome of monocytes recovered genes relevant for association to smoking and atherosclerosis, and connected genes that before, were only studied in separate contexts

  10. Inhibition of Endoplasmic Reticulum Stress and Atherosclerosis by 2-Aminopurine in Apolipoprotein E-Deficient Mice

    OpenAIRE

    Emmanuel Okoro; Zhong Mao Guo; Dong Fang Wu; Dezhi Yang; Lichun Zhou; Hong Yang

    2013-01-01

    We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE −/− ) mice, so called E−/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E−/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in a...

  11. Cardiorenal consequences of atherosclerosis and statins therapy: from the past to the future.

    Science.gov (United States)

    Buemi, Michele; Aloisi, Carmela; Fulvio, Floccari; Caccamo, Chiara; Cavallaro, Emanuela; Crascì, Eleonora; Criseo, Manila; Corica, Francesco; Frisina, Nicola

    2005-01-01

    Complications from atherosclerosis cause most deaths in western countries, and their incidence appears to be markedly increasing in developing countries, thus suggesting a correlation that is directly proportional to social progress. In recent years, the different branches of medical research, from studies on vascular disease to those on lipid and glucose metabolism, and also clinical research on coronary, carotid and peripheral artery diseases, epidemiologic and pharmacologic research, have concentrated on these diseases with the common aim of reducing the incidence of cardiovascular diseases, and mortality. Scientific progress has greatly improved our understanding of the pathogenic mechanisms underlying the progression of cardiovascular disease, and efforts in this discipline now appear more necessary than ever.

  12. Plasma Lipoprotein-associated Phospholipase A2 in Patients with Metabolic Syndrome and Carotid Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Mao Yong-jun

    2011-01-01

    Full Text Available Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2 is a recently identified and potentially useful plasma biomarker for cardiovascular and atherosclerotic diseases. However, the correlation between the Lp-PLA2 activity and carotid atherosclerosis remains poorly investigated in patients with metabolic syndrome (MetS. The present study aimed to evaluate the potential role of Lp-PLA2 as a comprehensive marker of metabolic syndrome in individuals with and without carotid atherosclerosis. Methods We documented 118 consecutive patients with MetS and 70 age- and sex-matched healthy subjects served as controls. The patients were further divided into two groups: 39 with carotid plaques and 79 without carotid plaques to elucidate the influence of Lp-PLA2 on carotid atherosclerosis. The plasma Lp-PLA2 activity was measured by using ELISA method and carotid intimal-media thickness (IMT was performed by ultrasound in all participants. Results Lp-PLA2 activity was significantly increased in MetS subgroups when compared with controls, and was higher in patients with carotid plaques than those without plaques (P 2 was obtained between patients with three and four disorders of metabolic syndrome (P P = 0.029, LDL-cholesterol (β = 0.401, P = 0.000 and waist-hip ratio (β = 0.410, P = 0.000 emerged as significant and independent determinants of Lp-PLA2 activity. Multiple stepwise regression analysis revealed that LDL-cholesterol (β = 0.309, P = 0.000, systolic blood pressure (β = 0.322, P = 0.002 and age (β = 0.235, P = 0.007 significantly correlated with max IMT, and Lp-PLA2 was not an independent predictor for carotid IMT. Conclusions Lp-PLA2 may be a modulating factor for carotid IMT via age and LDL-cholesterol, not independent predictor in the pathophysiological process of carotid atherosclerosis in patients with MetS.

  13. Characterization of atherosclerosis by histochemical and immunohistochemical methods in African grey parrots (Psittacus erithacus) and Amazon parrots (Amazona spp.).

    Science.gov (United States)

    Fricke, Cornelia; Schmidt, Volker; Cramer, Kerstin; Krautwald-Junghanns, Maria-Elisabeth; Dorrestein, Gerry M

    2009-09-01

    The aim of the study was to characterize atherosclerotic changes in African grey parrots (Psittacus erithacus) and Amazon parrots (Amazona spp.) by histochemical and immunohistochemical methods. Samples of the aorta ascendens and trunci brachiocephalici from 62 African grey parrots and 35 Amazon parrots were stained by hematoxylin and eosin and Elastica van Gieson for grading of atherosclerosis in these birds. Four different stages were differentiated. The incidence of atherosclerosis in the examined parrots was 91.9% in African grey parrots and 91.4% in Amazon parrots. To evaluate the pathogenesis in birds, immunohistochemical methods were performed to demonstrate lymphocytes, macrophages, smooth muscle cells, and chondroitin sulfate. According to the missing lymphocytes and macrophages and the absence of invasion and proliferation of smooth muscle cells in each atherosclerotic stage, "response-to-injury hypothesis" seems inapplicable in parrots. Additionally, we found alterations of vitally important organs (heart, lungs) significantly correlated with atherosclerosis of the aorta ascendens.

  14. Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52,000 individuals

    DEFF Research Database (Denmark)

    Kaur-Knudsen, D; Bojesen, S E; Nordestgaard, B G

    2009-01-01

    Cytochrome P450 2C9 (CYP2C9) enzymes metabolize warfarin and arachidonic acid. We hypothesized that the CYP2C9(*)2 (rs.1799853) and CYP2C9(*)3 (rs.1057910) polymorphisms with decreased enzyme activity affect risk of subclinical atherosclerosis (reduced ankle brachial index and increased C...... of follow-up; the Copenhagen General Population Study, a cross-sectional study including 21 629 participants; and the Copenhagen Ischemic Heart Disease Study, a case-control study including 5082 cases and 14 904 controls. CYP2C9 carriers versus noncarriers did not associate with subclinical atherosclerosis......% power. In conclusion, in three independent studies totaling more than 52 000 individuals, we found no association between CYP2C9(*)2 and CYP2C9(*)3 polymorphisms and risk of subclinical atherosclerosis, ischemic vascular disease or death after ischemic heart disease....

  15. A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo

    Science.gov (United States)

    Wu, Chenxin; Zhang, Yejun; Li, Zhen; Li, Chunyan; Wang, Qiangbin

    2016-06-01

    Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively accumulated in the region of atherosclerotic plaque due to the lipophilicity of the C18 chain to the atherosclerosis microenvironment, and thus the atherosclerosis was real-time monitored by high contrast-enhanced photoacoustic (PA) imaging of ICG. Combining the high signal-to-noise ratio (SNR) and high spatial resolution fluorescence imaging of Ag2S QDs in the second near-infrared window (NIR-II) and related histological assessment in vitro, the feasibility of this new nanoprobe for atherosclerosis targeting in an Apoe-/- mouse model was verified. Additionally, hemolysis and coagulation assays of the ICG@PEG-Ag2S revealed its decent hemocompatibility and no histological changes were observed in the main organs of the mouse. Such a simple, multifunctional nanoprobe for targeting and PA imaging of atherosclerosis will have a great potential for future clinical applications.Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively

  16. Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52 000 individuals

    DEFF Research Database (Denmark)

    Kaur-Knudsen, D.; Bojesen, S.E.; Nordestgaard, Børge

    2009-01-01

    Cytochrome P450 2C9 (CYP2C9) enzymes metabolize warfarin and arachidonic acid. We hypothesized that the CYP2C9*2 (rs. 1799853) and CYP2C9*3 (rs. 1057910) polymorphisms with decreased enzyme activity affect risk of subclinical atherosclerosis (reduced ankle brachial index and increased C-reactive ......Cytochrome P450 2C9 (CYP2C9) enzymes metabolize warfarin and arachidonic acid. We hypothesized that the CYP2C9*2 (rs. 1799853) and CYP2C9*3 (rs. 1057910) polymorphisms with decreased enzyme activity affect risk of subclinical atherosclerosis (reduced ankle brachial index and increased C......% power. In conclusion, in three independent studies totaling more than 52 000 individuals, we found no association between CYP2C9*2 and CYP2C9*3 polymorphisms and risk of subclinical atherosclerosis, ischemic vascular disease or death after ischemic heart disease. The Pharmacogenomics Journal (2009) 9...

  17. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

    Directory of Open Access Journals (Sweden)

    Savel J

    2012-06-01

    Full Text Available Julia Savel,1,2 Marianne Lafitte,1 Yann Pucheu,1,3 Vincent Pradeau,1 Antoine Tabarin,2,3 Thierry Couffinhal1,3,41Centre d'Exploration, de Prévention et de Traitement de l'Athérosclérose, Hôpital Cardiologique, 2Service d'endocrinologie, CHU Bordeaux, Université Bordeaux Segalen, Bordeaux, France; 3Université de Bordeaux Adaptation cardiovasculaire à l'ischémie, 4INSERM, Adaptation cardiovasculaire à l'ischémie, U1034, Pessac, FranceAbstract: A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.Keywords: atherosclerosis, LCAT function

  18. Urinary arsenic methylation capability and carotid atherosclerosis risk in subjects living in arsenicosis-hyperendemic areas in southwestern Taiwan

    International Nuclear Information System (INIS)

    Long-term exposure to inorganic arsenic from artesian drinking well water is associated with carotid atherosclerosis in the Blackfoot Disease (BFD)-hyperendemic area in Taiwan. The current study examined the arsenic methylation capacity and its risk on carotid atherosclerosis. A total of 304 adults (158 men and 146 women) residing in the BFD-hyperendemic area were included. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Chronic arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE) and the duration of artesian well water consumption. Urinary levels of inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] were determined by high performance liquid chromatography linked on-line to a hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). The percentage of arsenic species, primary methylation index [PMI = MMA(V) / (As(III) + As(V)] and secondary methylation index [SMI = DMA(V) / MMA(V)] were calculated and employed as indicators of arsenic methylation capacity. Results showed that women and younger subjects had a more efficient arsenic methylation capacity than did men and the elderly. Carotid atherosclerosis cases had a significantly greater percentage of MMA(V) [%MMA(V)] and a lower percentage of DMA [%DMA (V)] compared to controls. Subjects in the highest two tertiles of PMI with a median of CAE > 0 mg/L-year had an odds ratio (OR) and a 95% confidence interval (CI) of carotid atherosclerosis of 2.61 and 0.98-6.90 compared to those in the highest two tertiles of PMI with a CAE = 0 mg/L-year. We conclude that individuals with greater exposure to arsenic and lower capacity to methylate inorganic arsenic may be at a higher risk to carotid atherosclerosis

  19. Association of human carboxypeptidase E exon5 gene polymorphisms with angiographical characteristics of coronary atherosclerosis in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    Jie WANG; En-zhi JIA; Yun ZHANG; Zhi-jian YANG; Tie-bing ZHU; Lian-sheng WANG; Bo CHEN; Ke-jiang CAO; Jun HUANG; Wen-zhu MA

    2008-01-01

    Aim: To explore the association between 801C>T and 847C>T polymorphisms of the human carboxypeptidase E (CPE) gene exon5, which could cause hyperproinsulinemia, and the angiographical characteristics of coronary atherosclerosis. Methods: In total, 1044 consecutive patients who underwent coronary angiography for suspected or known coronary atherosclerosis were examined with respect to their genotypes, insulin, proinsulin level, and other risk factors of coronary atherosclerosis. The angiographical characteristics of coro-nary atherosclerosis (ie the severity of coronary heart disease) were defined by Gensini's score (GS) system. Results: The results showed that the genotype frequencies ofCC, CT, and TT at 801C>T locus were significantly different among the patients of the 4 groups who were classified by quartile values of GS (P=0.033). However, the frequency of the 847T allele was 0 for all the patients. The ordinal logistic regression analysis revealed that the increased risk of angiographical characteristics of coronary atherosclerosis were associated with CPE 801CT/TT variant genotypes [adjusted odds ratio (OR)=1.23, 95% confidence interval (CI) =0.93-1.63 for 801CT and adjusted OR=3.13, 95% CI=1.18-8.28 for 801TT] com-pared with the 801CC wild-type homozygotes. A stratification analysis showed that the effects of the CPE 801TT genotype were more evident among subgroups with relatively older (>=60 years) patients, males, and smokers. Furthermore, an analysis of covariance controlling age, sex, and body mass index indicated that differences of blood glucose, insulin, insulin resistance, and the proinsulin level between 801C>T genotype groups were not statistically significant. Conclusion: These findings indicate that the 801C>T polymorphism in the CPE exon5 gene may contribute to the angiographical characteristics of coronary atherosclerosis in the Chinese population.

  20. Non-invasive Detection of Aortic and Coronary Atherosclerosis in Homozygous Familial Hypercholesterolemia by 64 Slice Multi-detector Row Computed Tomography Angiography

    Science.gov (United States)

    Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector-row ...

  1. Extension of the mitochondria dysfunction hypothesis of metabolic syndrome to atherosclerosis with emphasis on the endocrine‐disrupting chemicals and biophysical laws

    OpenAIRE

    Lee, Hong Kyu; Shim, Eun Bo

    2013-01-01

    Abstract Metabolic syndrome and its component phenotypes, hyperglycemia, hypertension, (abdominal) obesity and hypertriglyceridemia, are major risk factors for atherosclerosis. Recently, associations between exposure to endocrine‐disrupting chemicals (EDCs), mitochondrial dysfunction, metabolic syndrome and atherosclerosis have been established, suggesting a possible common mechanism underlying these phenomena. Extending a previously proposed mitochondria dysfunction theory of metabolic syndr...

  2. Cytosolic triglycerides and oxidative stress in central obesity : the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure?

    NARCIS (Netherlands)

    Bakker, SJL; IJzerman, RG; Teerlink, T; Westerhoff, HV; Gans, ROB; Heine, RJ

    2000-01-01

    Central obesity is increasingly recognized as a risk factor for atherosclerosis and type 2 diabetes mellitus. Here we present a hypothesis that may explain the excess atherosclerosis, endothelial dysfunction and progressive beta-cell failure. Central obesity is associated with increased cytosolic tr

  3. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography

    Science.gov (United States)

    Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector row ...

  4. Inflammation, lipid metabolism dysfunction, and hypertension: Active research fields in atherosclerosis-related cardiovascular disease in China

    Institute of Scientific and Technical Information of China (English)

    YIN Kai; TANG ChaoKe

    2011-01-01

    Atherosclerosis-related cardiovascular disease is one of the leading causes of death in China [1].With advances in our understanding of the molecular mechanisms of atherosclerosis vascular inflammation,lipid metabolism dysfunction,and hypertension are regarded as the main pathogenetic pathways of both early atherogenesis and advanced plaque rupture [2,3].Currently,much attention is being paid to the control of these pathways,which offers the potential for development of novel therapeutic approaches in the treatment of cardiovascular disease in China.

  5. Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja Xenia; Bro, Susanne; Andersen, Mikkel H;

    2009-01-01

    OBJECTIVE: Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism...... and atherosclerosis in uremic apoE-/- mice. METHODS AND RESULTS: Upon intraperitoneal injection, h-apoA-I and TripA-I rapidly associated with plasma HDL and reduced mouse apoA-I plasma levels without affecting total or HDL cholesterol concentrations. The plasma half-life was approximately 36 h for Trip...

  6. The angiotensin II type 2 receptor agonist Compound 21 is protective in experimental diabetes-associated atherosclerosis

    DEFF Research Database (Denmark)

    Chow, Bryna S M; Koulis, Christine; Krishnaswamy, Pooja;

    2016-01-01

    AIMS/HYPOTHESIS: Angiotensin II is well-recognised to be a key mediator in driving the pathological events of diabetes-associated atherosclerosis via signalling through its angiotensin II type 1 receptor (AT1R) subtype. However, its actions via the angiotensin II type 2 receptor (AT2R) subtype...... are still poorly understood. This study is the first to investigate the role of the novel selective AT2R agonist, Compound 21 (C21) in an experimental model of diabetes-associated atherosclerosis (DAA). METHODS: Streptozotocin-induced diabetic Apoe-knockout mice were treated with vehicle (0.1 mol/l citrate...

  7. Long-term activation of the innate immune system in atherosclerosis.

    Science.gov (United States)

    Christ, Anette; Bekkering, Siroon; Latz, Eicke; Riksen, Niels P

    2016-08-01

    Efforts to reverse the pathologic consequences of vulnerable plaques are often stymied by the complex treatment resistant pro-inflammatory environment within the plaque. This suggests that pro-atherogenic stimuli, such as LDL cholesterol and high fat diets may impart longer lived signals on (innate) immune cells that persist even after reversing the pro-atherogenic stimuli. Recently, a series of studies challenged the traditional immunological paradigm that innate immune cells cannot display memory characteristics. Epigenetic reprogramming in these myeloid cell subsets, after exposure to certain stimuli, has been shown to alter the expression of genes upon re-exposure. This phenomenon has been termed trained innate immunity or innate immune memory. The changed responses of 'trained' innate immune cells can confer nonspecific protection against secondary infections, suggesting that innate immune memory has likely evolved as an ancient mechanism to protect against pathogens. However, dysregulated processes of immunological imprinting mediated by trained innate immunity may also be detrimental under certain conditions as the resulting exaggerated immune responses could contribute to autoimmune and inflammatory diseases, such as atherosclerosis. Pro-atherogenic stimuli most likely cause epigenetic modifications that persist for prolonged time periods even after the initial stimulus has been removed. In this review we discuss the concept of trained innate immunity in the context of a hyperlipidemic environment and atherosclerosis. According to this idea the epigenome of myeloid (progenitor) cells is presumably modified for prolonged periods of time, which, in turn, could evoke a condition of continuous immune cell over-activation.

  8. Endothelial Expression of Scavenger Receptor Class B, Type I Protects against Development of Atherosclerosis in Mice

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    Boris L. Vaisman

    2015-01-01

    Full Text Available The role of scavenger receptor class B, type I (SR-BI in endothelial cells (EC was examined in several novel transgenic mouse models expressing SR-BI in endothelium of mice with normal C57Bl6/N, apoE-KO, or Scarb1-KO backgrounds. Mice were also created expressing SR-BI exclusively in endothelium and liver. Endothelial expression of the Tie2-Scarb1 transgene had no significant effect on plasma lipoprotein levels in mice on a normal chow diet but on an atherogenic diet, significantly decreased plasma cholesterol levels, increased plasma HDL cholesterol (HDL-C levels, and protected mice against atherosclerosis. In 8-month-old apoE-KO mice fed a normal chow diet, the Tie2-Scarb1 transgene decreased aortic lesions by 24%. Mice expressing SR-BI only in EC and liver had a 1.5 ± 0.1-fold increase in plasma cholesterol compared to mice synthesizing SR-BI only in liver. This elevation was due mostly to increased HDL-C. In EC culture studies, SR-BI was found to be present in both basolateral and apical membranes but greater cellular uptake of cholesterol from HDL was found in the basolateral compartment. In summary, enhanced expression of SR-BI in EC resulted in a less atherogenic lipoprotein profile and decreased atherosclerosis, suggesting a possible role for endothelial SR-BI in the flux of cholesterol across EC.

  9. Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Natsume, Midori; Baba, Seigo

    2014-01-01

    Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p < 0.05). Pathological observations showed that accumulation of cholesterol crystals in the plaque area was greater in the control group compared with the 0.40 % cacao polyphenol group (p < 0.05). Immunochemical staining in the 0.25 and 0.40 % groups showed that expression of the cell adhesion molecules (VCAM-1 and ICAM-1) and production of oxidative stress markers (4-hydroxynonenal, hexanoyl-lysine, and dityrosine) were reduced in cross-sections of the brachiocephalic trunk. These results suggest that cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

  10. Crosstalk between Red Blood Cells and the Immune System and Its Impact on Atherosclerosis

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    Brigitta Buttari

    2015-01-01

    Full Text Available Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by inflammation, oxidative stress, and immune system activation. Evidence exists on a pathogenic role of oxidized red blood cells (RBCs accumulated in the lesion after intraplaque hemorrhage. This review reports current knowledge on the impact of oxidative stress in RBC modifications with the surface appearance of senescent signals characterized by reduced expression of CD47 and glycophorin A and higher externalization of phosphatidylserine. The review summarizes findings indicating that oxidized, senescent, or stored RBCs, due to surface antigen modification and release of prooxidant and proinflammatory molecules, exert an impaired modulatory activity on innate and adaptive immune cells and how this activity contributes to atherosclerotic disease. In particular RBCs from patients with atherosclerosis, unlike those from healthy subjects, fail to control lipopolysaccharide-induced DC maturation and T lymphocyte apoptosis. Stored RBCs, accompanied by shedding of extracellular vesicles, stimulate peripheral blood mononuclear cells to release proinflammatory cytokines, augment mitogen-driven T cell proliferation, and polarize macrophages toward the proinflammatory M1 activation pathway. Collectively, literature data suggest that the crosstalk between RBCs with immune cells represents a novel mechanism by which oxidative stress can contribute to atherosclerotic disease progression and may be exploited for therapeutic interventions.

  11. Selected thrombosis and atherosclerosis risk factors in children with idiopathic nephrotic syndrome

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    Beata Bieniaś

    2012-04-01

    Full Text Available The purpose of our study was to evaluate selected thrombosis and atherosclerosis risk factors in children with idiopathic nephrotic syndrome (INS at three  stages of the disease (I – in acute phase before steroid therapy, II – during steroid therapy after resolution of proteinuria, III – in remission after completion of steroid therapy.In all children, serum total homocysteine, lipoprotein (a, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels were measured at three stages of the disease. Plasma antithrombin III, fibrinogen and D-dimer levels were also determined.  At all stages of INS, the serum t-HCY levels were similar and significantly higher than in controls.  Serum lipoprotein (a level, plasma antithrombin III, fibrinogen and D-dimer levels were significantly higher at stage I than at stages II, III and controls.In conclusion, children with INS are at high risk of thrombosis and atherosclerosis. Keywords: Idiopathic nephrotic syndrome, Homocysteine, Lipoprotein (a, Antithrombin III, fibrinogen, D-dimer

  12. Assessment of the co-incidence between non alcoholic fatty liver disease and carotid atherosclerosis.

    Science.gov (United States)

    El-Sayed, Sohair Abd El-Kader; El-Folly, Runia Fouad; Ahmed, Amr Mahmmoud

    2014-04-01

    Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of abnormal liver biochemistry and cryptogenic cirrhosis. Those with NAFLD have a higher prevalence of atherosclerosis, as shown by increased carotid artery intimal media thickness (CIMT). The aim of this study is to assess the co-incidence and prevalence between NAFLD and carotid atherosclerosis. In this study seventy-two subjects were categorized into 2 groups. GI: 52 patients diagnosed as NAFLD with diabetes mellitus type 2 or obesity or hyperlipedemia. GII: 20 diseased controls diagnosed as NAFLD without other predisposing factor. CIMT and plaque prevalence were estimated by carotid ultrasonography as a single trained operator who was blind to clinical characteristics of participants. The results showed that CIMT by carotid duplex ultrasonography was significantly higher in group A than group B but CIMT did not reveal any significant difference as regards to the etiology of NAFLD. CIMT was significantly higher in cases with bright liver than those with homogenous liver (by abdominal US) in group I and II. CIMT was significantly higher in those with moderate steatosis than those with mild steatosis (in GI & GII).

  13. EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

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    R MAHDAVI

    2003-03-01

    Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

  14. Atherosclerosis of Coronary Arteries as Predisposing Factor in Myocardial Infarction: An Autopsy Study

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    Gauravi A Dhruva,

    2012-10-01

    Full Text Available The incidence of coronary heart disease has markedly increased in India over the past few years. Ischemic heart disease, the largest cause of morbidity and mortality in the developed and developing countries today is overwhelmingly contributed by atherosclerosis. The study highlights the impact of atherosclerotic lesions in the population of Rajkot district. We studied atherosclerotic lesions in coronary arteries in cases subjected to autopsy in last 4 years, to grade and to evaluate the atheromatous plaques; and to assess the cases of myocardial infarction amongst them. The study comprises dissected specimens of heart in total 360 cases subjected for autopsy. The vessels were examined for the presence of atherosclerotic lesions which were graded according to American Heart Association and examined for evidence of myocardial infarction. The study comprises the cases in age group between 20 to 80 years. Commonest type of atherosclerosis seen was grade-4. Left Anterior Descending Coronary was most commonly involved artery. Myocardial infarction was the cause of death in 35 cases (9.72% The data obtained may form a baseline for the forthcoming studies.

  15. Neoatherosclerosis:Coronary stents seal atherosclerotic lesions but result in making a new problem of atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Hidenori; Komiyama; Masamichi; Takano; Noritake; Hata; Yoshihiko; Seino; Wataru; Shimizu; Kyoichi; Mizuno

    2015-01-01

    Chronic inflammation of the native vessel wall with infiltration of lipid-laden foamy macrophages through impaired endothelium results in atherosclerosis. Percutaneous coronary intervention, including metallic stent implantation, is now widely utilized for the treatment of atherosclerotic lesions of the coronary artery. Baremetal stents and the subsequently developed drugeluting stents seal the atherosclerosis and resolve lumen stenosis or obstruction of the epicardial coronary artery and myocardial ischemia. After stent implantation, neointima proliferates within the stented segment. Chronic inflammation caused by a foreign body reaction to the implanted stent and subsequent neovascularization, which is characterized by the continuous recruitment of macrophages into the vessel, result in the transformation of the usual neointima into an atheromatous neointima. Neointima with an atherosclerotic appearance, such as that caused by thin-cap fibroatheromas, is now recognized as neoatherosclerosis, which can sometimes cause in-stent restenosis and acute thrombotic occlusion originating from the stent segment following disruption of the atheroma. Neoatherosclerosis is emerging as a new coronary stent-associated problem that has not yet been resolved. In this review article, we will discuss possible mechanisms, clinical challenges, and the future outlook of neoatherosclerosis.

  16. Effect of Ozone Produced from Antibody-catalyzed Water Oxidation on Pathogenesis of Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun PENG; Yu-Shan HUANG; Li-Na AN; Xiao-Qun HAN; Jing-Ge ZHANG; Qiu-Lin WANG; Jing SUN; Shu-Ren WANG

    2006-01-01

    Recent studies have suggested that antibodies can catalyze the generation of unknown oxidants including hydrogen peroxide (H2O2) and ozone (O3) from singlet oxygen (1O2) and water. This study is aimedto detect the effect of antibody-catalyzed water oxidation on atherosclerosis. Our results showed that both H2O2 and O3 were produced in human leukemia THP- 1 monocytes incubated with human immunoglobulin G and phorbol myristate acetate. In the THP-1 monocytes incubated with human immunoglobulin G, phorbol myristate acetate and low density lipoprotein, the intracellular total cholesterol, free cholesterol, cholesteryl ester and lipid peroxides clearly increased, and a larger number of foam cells were observed by oil red O staining. The accumulation of all intracellular lipids was significantly inhibited by vinylbenzoic acid, and only slightly affected by catalase. These findings suggested that the production of O3, rather than H2O2, might be involved in the pathogenesis of atherosclerosis through the antibody-catalyzed water oxidation pathway.

  17. Emotional intelligence and coronary atherosclerosis: exploratory study using the Trait Meta-Mood Scale

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    Mariana Suárez-Bagnasco

    2013-12-01

    Full Text Available Introduction There are no prior studies that assess emotional intelligence in asymptomatic adults with coronary atherosclerosis. Aim The purpose of this study is to explore associations between emotional intelligence in asymptomatic adults with and without coronary atherosclerotic lesions. Design and method Cross-sectional design. The sample consisted of 100 asymptomatic 30 to 80 year-old adults that met the inclusion and exclusion criteria and who underwent coronary multislice computed tomography. Coronary atherosclerosis was shown by 64-channel multislice computed tomography. Emotional intelligence was assessed by applying the Trait Meta-Mood Scale. Results The sample was composed of 73% men and 27% women. Fifty-one percent had coronary atherosclerotic lesions, 78% had scores below the reference values for both Clarity and Repair. Seventy-nine percent had scores above the reference values for Attention. Statistically significant associations were found between the presence of coronary atherosclerotic lesion and: a emotional attention, chi-square: 0.302, p=0.043, b emotional clarity, chi-square: -0.312, p=0.040, b emotional regulation, chi-square: -0.313, p=0.040. Conclusions: People with coronary atherosclerotic lesions showed an excessive tendency to focus on their own feelings and higher levels of rumination, together with lower ability to identify, distinguish and describe their emotions. Likewise, they have lower ability to reduce or eliminate negative emotions and to increase or maintain the intensity of positive emotions.

  18. Therapeutic Potential of Ocimum tenuiflorum as MPO Inhibitor with Implications for Atherosclerosis Prevention.

    Science.gov (United States)

    Narasimhulu, Chandrakala Aluganti; Vardhan, Sangamithra

    2015-05-01

    Current experimental studies show that Ocimum tenuiflorum (commonly known as basil or Tulsi) possesses many health benefits. Ocimum is suggested to be antioxidative and anti-inflammatory. Eugenol, an orthomethoxyphenol, and ursolic acid have been identified as important components of basil. Myeloperoxidase (MPO), an oxidative enzyme, has been implicated in the pathogenesis of atherosclerosis. MPO-dependent oxidation of lipoproteins has been implicated in foam cell formation, dysfunctional HDL, and abnormalities in reverse cholesterol transport. Whole leaf extract of O. tenuiflorum and its major components, eugenol and ursolic acid, inhibit the oxidation of lipoproteins by myeloperoxidase/copper as measured by conjugated diene formation as well as by the thiobarbituric acid reactive substance (TBARS) assay. Whole basil leaf extract is able to attenuate the lipopolysaccharide-induced inflammation in RAW 264.7 cells compared with its components. In addition, whole basil leaf extract and eugenol inhibited MPO enzyme activity against synthetic substrates. Based on these results, we conclude that basil extract could act as an inhibitor of MPO and may serve as a nonpharmacological therapeutic agent for atherosclerosis.

  19. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

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    Falk eWeih

    2012-07-01

    Full Text Available Tertiary lymphoid organs (TLOs emerge in tissues in response to nonresolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE-/- mice. ATLOs are structured into T cell areas harboring conventional dendritic cells (cDCs and monocyte-derived DCs (mDCs; B cell follicles containing follicular dendritic cells (FDCs within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4+ and CD8+ effector T cells, natural and induced CD4+ T regulatory cells (nTregs; iTregs as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses towards atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease.

  20. Endothelial dysfunction and atherosclerosis in children with irreversible pulmonary hypertension due to congenital heart disease

    International Nuclear Information System (INIS)

    To assess endothelial dysfunction and the risk for coronary atherosclerosis in children with irreversible pulmonary hypertension due to congenital heart disease (CHD). The study included 18 cyanotic patients (the mean age was 12.28 ± 3.26 years) who developed irreversible pulmonary hypertension due to cyanotic and acyanotic CHDs, and 18 control patients (the mean age was 11.78 ± 3.00 years). Study groups were compared for flow-mediated dilatation (FMD), carotid intima media thickness (CIMT) and atherosclerotic risk factors. Compared to the control group, the mean FMD was significantly reduced in the cyanotic group (5.26 ± 2.42% and 9.48 ± 2.60%, respectively; P-value < 0.001). No significant difference was observed between the groups in CIMT (0.41 ± 0.08 mm and 0.39 ± 0.06 mm, respectively; P-value = 0.299). The levels of total cholesterol, low-density lipoprotein–cholesterol and very low-density lipoprotein–cholesterol were statistically significantly lower compared tothe control group (P-value = 0.001, 0.006 and 0.014, respectively), whereas no statistically significant difference was found in the levels of high-density lipoprotein–cholesterol and triglycerides (P-value = 0.113 and 0.975, respectively). Systemic endothelial dysfunction in children with irreversible pulmonary hypertension due to CHD was noted but there was no increased risk for atherosclerosis