WorldWideScience

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. Atherosclerosis and Stroke

    Science.gov (United States)

    ... Inspirational Stories Stroke Heroes Among Us Atherosclerosis and Stroke Updated:Oct 24,2016 Excerpted and adapted from " ... it can cause difficulty walking and eventually gangrene. Stroke and atherosclerosis There are two types of ischemic ...

  4. Vaccination to Modulate Atherosclerosis

    Science.gov (United States)

    Kimura, Takayuki; Tse, Kevin; Sette, Alessandro; Ley, Klaus

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of the artery wall. Adaptive immunity plays a key role in the pathogenesis of atherosclerosis. Recently, modulation of the immune response against atherosclerotic plaque antigen(s) has attracted attention as a potentially preventive and therapeutic approach. Here we review a series of studies on immunization with various antigens targeting treatment and prevention of atherosclerosis. Atherosclerosis-related antigens include oxidized LDL, apolipoprotein B-100, and heat shock protein 60/65. Accumulating evidence supports the idea that immunization with these antigenic proteins or peptides may reduce atherosclerosis. In this review, we discuss the current status of immunization studies and possible associated mechanisms of atheroprotection. PMID:25683179

  5. Inflammasomes and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    S. Vallurupalli, MD

    2016-09-01

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

  6. Vaccination against atherosclerosis

    NARCIS (Netherlands)

    Es, Thomas van

    2009-01-01

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

  7. 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. Copyright © 2015. Published by Elsevier Ireland Ltd.

  8. How Is Atherosclerosis Treated?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  9. How Is Atherosclerosis Diagnosed?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  10. What Is Atherosclerosis?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  11. What Causes Atherosclerosis?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  12. Living with Atherosclerosis

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  13. Infection and Atherosclerosis Development

    Science.gov (United States)

    Campbell, Lee Ann; Rosenfeld, Michael E.

    2015-01-01

    Atherosclerosis is a chronic disease hallmarked by chronic inflammation, endothelial dysfunction and lipid accumulation in the vasculature. Although lipid modification and deposition are thought to be a major source of the continuous inflammatory stimulus, a large body of evidence suggests that infectious agents may contribute to atherosclerotic processes. This could occur by either direct effects through infection of vascular cells and/or through indirect effects by induction of cytokine and acute phase reactant proteins by infection at other sites. Multiple bacterial and viral pathogens have been associated with atherosclerosis by seroepidemiological studies, identification of the infectious agent in human atherosclerotic tissue, and experimental studies demonstrating an acceleration of atherosclerosis following infection in animal models of atherosclerosis. This review will focus on those infectious agents for which biological plausibility has been demonstrated in animal models and on the challenges of proving a role of infection in human atherosclerotic disease. PMID:26004263

  14. [Epigenetics in atherosclerosis].

    Science.gov (United States)

    Guardiola, Montse; Vallvé, Joan C; Zaina, Silvio; Ribalta, Josep

    2016-01-01

    The association studies based on candidate genes carried on for decades have helped in visualizing the influence of the genetic component in complex diseases such as atherosclerosis, also showing the interaction between different genes and environmental factors. Even with all the knowledge accumulated, there is still some way to go to decipher the individual predisposition to disease, and if we consider the great influence that environmental factors play in the development and progression of atherosclerosis, epigenetics is presented as a key element in trying to expand our knowledge on individual predisposition to atherosclerosis and cardiovascular disease. Epigenetics can be described as the discipline that studies the mechanisms of transcriptional regulation, independent of changes in the sequence of DNA, and mostly induced by environmental factors. This review aims to describe what epigenetics is and how epigenetic mechanisms are involved in atherosclerosis. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  15. Phytosterols and atherosclerosis

    DEFF Research Database (Denmark)

    Schrøder, Malene

    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...

  16. Integrin signaling in atherosclerosis.

    Science.gov (United States)

    Finney, Alexandra C; Stokes, Karen Y; Pattillo, Christopher B; Orr, A Wayne

    2017-06-01

    Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the development of advanced fibrotic plaques. Integrin signaling has been shown to regulate endothelial phenotype, facilitate leukocyte homing, affect leukocyte function, and drive smooth muscle fibroproliferative remodeling. In addition, integrin signaling in platelets contributes to the thrombotic complications that typically drive the clinical manifestation of cardiovascular disease. In this review, we examine the current literature on integrin regulation of atherosclerotic plaque development and the suitability of integrins as potential therapeutic targets to limit cardiovascular disease and its complications.

  17. 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...... for decades for their natural ability to reduce cholesterol levels in the blood. In the last decade numerous food products added phytosterol esters have been placed on the market, e.g. yellow fat spread, yoghurt, dressing. The products are being marketed as a natural means for people who want to lower...

  18. Molecular imaging in atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Glaudemans, Andor W.J.M.; Slart, Riemer H.J.A. [Dept. of Nuclear Medecine and Molecular Imaging, Groningen Univ. (Netherlands); Bozzao, Alessandro [Dept. of Neuroradiology, Univ. Rome (Italy); Bonanno, Elena [Univ. Tor Vergata, Rome (Italy). Dept. of Biopathologoy and Diagnostic Imaging; Arca, Marcello [Univ. Rome (Italy). 1. Faculty of Medicine; Dierckx, Rudi A.J.O. [Dept. of Nuclear Medecine and Molecular Imaging, Groningen Univ. (Netherlands); Ghent Univ. (Belgium); Signore, Alberto [Dept. of Nuclear Medecine and Molecular Imaging, Groningen Univ. (Netherlands); Univ. Rome (Italy). 2. Faculty of Medicine; Univ. of Rome (Italy). Medicina Nucleare Ospedale

    2010-12-15

    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 (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  19. Molecular imaging in atherosclerosis

    Science.gov (United States)

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

    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 (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  20. Phosphatidylserine in atherosclerosis

    OpenAIRE

    Darabi, Maryam; Kontush, Anatol

    2016-01-01

    International audience; Purpose of review: It is now widely acknowledged that phosphatidylserine is a multifunctional bioactive lipid. In this review, we focus on the function of phosphatidylserine in modulating cholesterol metabolism, influencing inflammatory response and regulating coagulation system, and discuss promising phosphatidylserine-based therapeutic approaches and detection techniques in atherosclerosis.

  1. 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.

  2. [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.

  3. Animal Models of Atherosclerosis

    Science.gov (United States)

    Getz, Godfrey S.; 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 manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

  4. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    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.

  5. Insulin resistance and atherosclerosis

    OpenAIRE

    Semenkovich, Clay F.

    2006-01-01

    Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent fi...

  6. 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.

  7. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Foppa Murilo

    2001-01-01

    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.

  8. ABC Transporters, Atherosclerosis and Inflammation

    OpenAIRE

    Fitzgerald, Michael L.; Mujawar, Zahedi; Tamehiro, Norimasa

    2010-01-01

    Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangi...

  9. Macrovascular disease and atherosclerosis in SSc

    NARCIS (Netherlands)

    Hettema, M. E.; Bootsma, H.; Kallenberg, C. G. M.

    Atherosclerosis is considered to be a chronic inflammatory disorder. Several autoimmune rheumatic diseases are characterized by premature and accelerated atherosclerosis in which both classical and non-classical risk factors contribute to atherogenesis. SSc is characterized by vasculopathy, and

  10. Trained innate immunity and atherosclerosis.

    Science.gov (United States)

    Bekkering, Siroon; Joosten, Leo A B; van der Meer, Jos W M; Netea, Mihai G; Riksen, Niels P

    2013-12-01

    Monocytes/macrophages play a decisive role in the development and progression of atherosclerosis. It is currently unknown what stimuli initiate and orchestrate the activation of these cells in atherogenesis. In this review, we postulate that the novel concept of 'trained immunity' modulates the development and progression of atherosclerosis. Recently, results from our laboratory challenged the current paradigm that innate immunity is static and does not have an immunological memory. Stimulation by various microbial products, including Candida albicans and bacille Calmette-Guérin, appeared to bring monocytes into a long-term enhanced functional state, showing a stronger proinflammatory response to a second stimulus. This 'trained immunity' was mediated by increased and stable histone methylation. We describe the hypothesis that this functional reprogramming of monocytes, either by microbial products or by metabolic products, contributes to atherogenesis and propose epigenetic reprogramming of monocytes as a novel pharmacological target for preventing or treating atherosclerosis in the future.

  11. Periodontal Innate Immune Mechanisms Relevant to Atherosclerosis

    OpenAIRE

    Amar, Salomon; Engelke, Marianne

    2014-01-01

    Atherosclerosis is a common cardiovascular disease in the United States. The disease is a leading cause of illness and death in the United States. Atherosclerosis is the most common cause for heart attack and stroke. Most commonly, people develop atherosclerosis as a result of diabetes, genetic risk factors, high blood pressure, a high-fat diet, obesity, high blood cholesterol levels, and smoking. However a sizable amount of patients suffering from atherosclerosis do not harbor the classical ...

  12. Long noncoding RNAs and atherosclerosis.

    Science.gov (United States)

    Zhou, Tian; Ding, Jia-wang; Wang, Xin-an; Zheng, Xia-xia

    2016-05-01

    Atherosclerosis is universally recognized as a chronic lipid-induced inflammation of the vessel wall in response to dyslipidemia and haemodynamic stress involving dysfunction and activation of resident vascular cells as well as infiltration of leukocytes. As members of nonprotein-coding RNAs, the long noncoding RNAs (lncRNAs) are implicated in various biological processes. Accumulating evidences suggest that lncRNAs regulate the function of vascular wall, activation of macrophages, lipid metabolism and immune response. Here, we review the effects of lncRNAs on the progress of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Preventing and arresting coronary atherosclerosis.

    Science.gov (United States)

    Roberts, W C

    1995-09-01

    The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.

  14. Inflammation and coagulation in atherosclerosis.

    Science.gov (United States)

    Krychtiuk, K A; Kastl, S P; Speidl, W S; Wojta, J

    2013-01-01

    Cardiovascular diseases remain to be the leading cause of death in Western societies. Despite major findings in vascular biology that lead to a better understanding of the pathomechanisms involved in atherosclerosis, treatment of the disease has only changed slightly within the last years. A big body of evidence suggests that atherosclerosis is a chronic inflammatory disease of the vessel wall. Accumulation and peroxidation of LDL-particles within the vessel wall trigger a strong inflammatory response, causing macrophage and T-cell accumulation within the vessel wall. Additionally, B-cells and specific antibodies against LDL-particles, as well as the complement system are implicated in atherogenesis. Besides data from clinical trials and autopsy studies it was the implementation of mouse models of atherosclerosis and the emerging field of direct gen-modification that lead to a thorough description of the pathophysiological mechanisms involved in the disease and created overwhelming evidence for a participation of the immune system. Recently, the cross-talk between coagulation and inflammation in atherogenesis has gained attention. Serious limitations and disparities in the pathophysiology of atherosclerosis in mice and men complicated the translation of experimental data into clinical practice. Despite these limitations, new anti-inflammatory medical therapies in cardiovascular disease are currently being tested in clinical trials.

  15. Intravital Microscopy for Atherosclerosis Research

    NARCIS (Netherlands)

    Megens, Remco T. A.; Soehnlein, Oliver

    2015-01-01

    Recruitment of leukocytes into arteries is a hallmark event throughout all stages of atherosclerosis and hence stands out as a primary therapeutic target. To understand the molecular mechanisms of arterial leukocyte subset infiltration, real-time visualization of recruitment processes of leukocyte

  16. Trained innate immunity and atherosclerosis

    NARCIS (Netherlands)

    Bekkering, S.; Joosten, L.A.B.; Meer, J.W.M. van der; Netea, M.G.; Riksen, N.P.

    2013-01-01

    PURPOSE OF REVIEW: Monocytes/macrophages play a decisive role in the development and progression of atherosclerosis. It is currently unknown what stimuli initiate and orchestrate the activation of these cells in atherogenesis. In this review, we postulate that the novel concept of 'trained immunity'

  17. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    DEFF Research Database (Denmark)

    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....

  18. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  19. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    OpenAIRE

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role o...

  20. DONOR-TRANSMITTED CORONARY ATHEROSCLEROSIS

    Directory of Open Access Journals (Sweden)

    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.

  1. [Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

    Science.gov (United States)

    Kohara, Katsuhiko

    2014-10-01

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

  2. 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.

  3. Systemic atherosclerosis and voiding symptom.

    Science.gov (United States)

    Yeniel, A Ozgur; Ergenoglu, A Mete; Meseri, Reci; Ari, Anıl; Sancar, Ceren; Itil, Ismail Mete

    2017-03-01

    To evaluate the effect of atherosclerosis on the storage and voiding symptoms of the bladder in women with overactive bladder (OAB). We retrospectively reviewed the charts of women with OAB who were evaluated between 2013 and 2015 in our urogynecology unit. Charts were assessed for history, examination findings, urinary diary, quality of life (QOL) questionnaires, urodynamic studies (UDSs), and four main risk factors for atherosclerosis: hypertension, diabetes mellitus, smoking, and hyperlipidemia. In a previous study, these were defined as vascular risk factors. Cases were excluded for insufficient data, diabetes mellitus with dysregulated blood glucose, or prolapse greater than 1cm to avoid confusing bladder outlet obstruction. We included 167 eligible cases in this study. We evaluated storage and voiding symptoms such as frequency, nocturia, residual urine volume, and voiding difficulties and UDS findings such as maximum bladder capacity, first desire, strong desire, detrusor overactivity, and bladder contractility index. The vascular risk score was categorized as "no risk" if the woman did not have any of the four risk factors and "at risk" if she had any of the factors. Independent sample t-test and chi-square tests were performed for analyses. Among the participants (n=167), 71.9% had at least one vascular risk factor. Those who were at risk were facing significantly more wet-type OAB (p=0.003) and nocturia (p=0.023). Moreover, mean age (p=0.008) and mean gravidity (p=0.020) were significantly higher in the at-risk group, whereas mean total nocturia QOL questionnaire scores (p=0.029) were significantly lower. Our findings suggest that aging and atherosclerosis may be associated with severe OAB and poorer QOL. Nocturia and related parameters of poor quality can be explained by impaired bladder neck perfusion. Future trials need to assess vascular and molecular changes in women with OAB. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    Science.gov (United States)

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role of hyperglycemia in CAD associated with type 2 diabetes is less clear. Understanding the mechanisms whereby type 2 diabetes exacerbates CAD offers hope for new therapeutic strategies to prevent and treat atherosclerotic vascular disease. PMID:22055501

  5. ABC transporters, atherosclerosis and inflammation.

    Science.gov (United States)

    Fitzgerald, Michael L; Mujawar, Zahedi; Tamehiro, Norimasa

    2010-08-01

    Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1

  6. Therapeutic approaches to drug targets in atherosclerosis.

    Science.gov (United States)

    Jamkhande, Prasad G; Chandak, Prakash G; Dhawale, Shashikant C; Barde, Sonal R; Tidke, Priti S; Sakhare, Ram S

    2014-07-01

    Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis.

  7. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    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

  8. Aging, progenitor cell exhaustion, and atherosclerosis.

    Science.gov (United States)

    Rauscher, Frederick M; Goldschmidt-Clermont, Pascal J; Davis, Bryce H; Wang, Tao; Gregg, David; Ramaswami, Priya; Pippen, Anne M; Annex, Brian H; Dong, Chunming; Taylor, Doris A

    2003-07-29

    Atherosclerosis is largely attributed to chronic vascular injury, as occurs with excess cholesterol; however, the effect of concomitant vascular aging remains unexplained. We hypothesize that the effect of time in atherosclerosis progression is related to obsolescence of endogenous progenitor cells that normally repair and rejuvenate the arteries. Here we show that chronic treatment with bone marrow-derived progenitor cells from young nonatherosclerotic ApoE-/- mice prevents atherosclerosis progression in ApoE-/- recipients despite persistent hypercholesterolemia. In contrast, treatment with bone marrow cells from older ApoE-/- mice with atherosclerosis is much less effective. Cells with vascular progenitor potential are decreased in the bone marrow of aging ApoE-/- mice, but cells injected from donor mice engraft on recipient arteries in areas at risk for atherosclerotic injury. Our data indicate that progressive progenitor cell deficits may contribute to the development of atherosclerosis.

  9. Atherosclerosis

    Science.gov (United States)

    ... State SELECT YOUR LANGUAGE Español (Spanish) 简体中文 (Traditional Chinese) 繁体中文 (Simplified Chinese) Tiếng Việt (Vietnamese) Healthy Living for Heart.org ... and Live Our Interactive Cardiovascular Library has detailed animations and illustrations to help you learn about conditions, ...

  10. Platelets and the complement cascade in atherosclerosis.

    Science.gov (United States)

    Patzelt, Johannes; Verschoor, Admar; Langer, Harald F

    2015-01-01

    Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will focus on roles for platelets in the onset as well as progression of the disease, a possible dual role for complement in the genesis and development of atherosclerosis, and review emerging literature revealing previously unrecognized cross-talk between platelets and the complement system and discuss its possible impact for atherosclerosis. Finally, we identify limitations of current research approaches and discuss perspectives of complement modulation in the control of the disease.

  11. Plasma metabolomics reveals biomarkers of the atherosclerosis.

    Science.gov (United States)

    Chen, Xi; Liu, Lian; Palacios, Gustavo; Gao, Jie; Zhang, Ning; Li, Guang; Lu, Juan; Song, Ting; Zhang, Yingzhi; Lv, Haitao

    2010-09-01

    Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in industrialized societies. The lack of metabolite biomarkers has impeded the clinical diagnosis of atherosclerosis so far. In this study, stable atherosclerosis patients (n=16) and age- and sex-matched non-atherosclerosis healthy subjects (n=28) were recruited from the local community (Harbin, P. R. China). The plasma was collected from each study subject and was subjected to metabolomics analysis by GC/MS. Pattern recognition analyses (principal components analysis, orthogonal partial least-squares discriminate analysis, and hierarchical clustering analysis) commonly demonstrated plasma metabolome, which was significantly different from atherosclerotic and non-atherosclerotic subjects. The development of atherosclerosis-induced metabolic perturbations of fatty acids, such as palmitate, stearate, and 1-monolinoleoylglycerol, was confirmed consistent with previous publication, showing that palmitate significantly contributes to atherosclerosis development via targeting apoptosis and inflammation pathways. Altogether, this study demonstrated that the development of atherosclerosis directly perturbed fatty acid metabolism, especially that of palmitate, which was confirmed as a phenotypic biomarker for clinical diagnosis of atherosclerosis.

  12. 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....

  13. Regulatory T Cell Immunity in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Hilman Zulkifli Amin

    2017-04-01

    Full Text Available Atherosclerosis is a chronic inflammatory disorder involving innate and adaptive immunity process. Effector T cell (Teff responses promote atherosclerotic disease, whereas regulatory T cells (Tregs have been shown to play a protective role against atherosclerosis by down-regulating inflammatory responses which include multiple mechanisms. Compelling experimental data suggest that shifting the Treg/Teff balance toward Tregs may be a possible therapeutic approach for atherosclerotic disease, although the role of Tregs in human atherosclerotic disease has not been fully elucidated. In this review, we discuss recent advances in our understanding of the roles of Tregs and Teffs in experimental atherosclerosis, as well as human coronary artery disease.

  14. How Can Atherosclerosis Be Prevented or Delayed?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  15. Who Is at Risk for Atherosclerosis?

    Science.gov (United States)

    ... disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease ... This may be an early sign of CHD. Stress Testing During stress testing , you exercise to make ...

  16. Accelerated atherosclerosis in patients with Wegener's granulomatosis

    NARCIS (Netherlands)

    de Leeuw, K; Sanders, J-S; Stegeman, C; Smit, A.; Kallenberg, C G; Bijl, M

    2005-01-01

    BACKGROUND: Several autoimmune disorders are complicated by excess cardiovascular disease. In addition to traditional risk factors, non-traditional risk factors such as endothelial activation and excessive vascular remodelling might be determinants of the progression of atherosclerosis in patients

  17. 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...

  18. 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.

  19. Secondary retroperitoneal fibrosis associated with generalized atherosclerosis.

    Science.gov (United States)

    Barbullushi, M; Pasko, N; Bezhani, E; Duraku, A; Rusi, R; Hoti, K; Bakalli, V; Idrizi, A

    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 arterial compromise.

  20. 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.

  1. Angiotensin converting enzyme 2 and atherosclerosis.

    Science.gov (United States)

    Wang, Yutang; Tikellis, Chris; Thomas, Merlin C; Golledge, Jonathan

    2013-01-01

    Angiotensin converting enzyme 2 (ACE2) is a homolog of angiotensin converting enzyme (ACE) which generates angiotensin II from angiotensin I. ACE, its product angiotensin II and the downstream angiotensin type I receptor are important components of the renin-angiotensin system (RAS). Angiotensin II, the most important component of the RAS, promotes the development of atherosclerosis. The identification of ACE2 in 2000 opened a new chapter of research on the regulation of the RAS. ACE2 degrades pro-atherosclerotic angiotensin II and generates anti-atherosclerotic angiotensin 1-7. In this review, we explored the importance of ACE2 in protecting experimental animals from developing atherosclerosis and its involvement in human atherosclerosis. We also examined the published evidence assessing the importance of ACE2 in different cell types relevant to atherosclerosis and putative underlying cellular and molecular mechanisms linking ACE2 with protection from atherosclerosis. ACE2 shifts the balance from angiotensin II to angiotensin 1-7 inhibiting the progression of atherosclerosis in animal models. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Periodontal innate immune mechanisms relevant to atherosclerosis.

    Science.gov (United States)

    Amar, S; Engelke, M

    2015-06-01

    Atherosclerosis is a common cardiovascular disease in the USA where it is a leading cause of illness and death. Atherosclerosis is the most common cause for heart attack and stroke. Most commonly, people develop atherosclerosis as a result of diabetes, genetic risk factors, high blood pressure, a high-fat diet, obesity, high blood cholesterol levels, and smoking. However, a sizable number of patients suffering from atherosclerosis do not harbor the classical risk factors. Ongoing infections have been suggested to play a role in this process. Periodontal disease is perhaps the most common chronic infection in adults with a wide range of clinical variability and severity. Research in the past decade has shed substantial light on both the initiating infectious agents and host immunological responses in periodontal disease. Up to 46% of the general population harbors the microorganism(s) associated with periodontal disease, although many are able to limit the progression of periodontal disease or even clear the organism(s) if infected. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. This review focuses on exploring the molecular consequences of infection by pathogens that exacerbate atherosclerosis, with the focus on infections by the periodontal bacterium Porphyromonas gingivalis as a running example. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  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. Cyanotic congenital heart disease and atherosclerosis.

    Science.gov (United States)

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

    2017-06-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C; Bielak, Lawrence F; Cox, Amanda J; Dörr, Marcus; Feitosa, Mary F; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikäinen, Leo-Pekka; Marioni, Riccardo E; Schminke, Ulf; Stitziel, Nathan O; Tada, Hayato; van Setten, Jessica|info:eu-repo/dai/nl/345493990; Smith, Albert V; Vojinovic, Dina; Yanek, Lisa R; Yao, Jie; Yerges-Armstrong, Laura M; Amin, Najaf; Baber, Usman; Borecki, Ingrid B; Carr, J Jeffrey; Chen, Yii-Der Ida; Cupples, L Adrienne; de Jong, Pim A|info:eu-repo/dai/nl/287955672; de Koning, Harry; de Vos, Bob D|info:eu-repo/dai/nl/413986004; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H; Goodarzi, Mark O; Harris, Tamara B; Heckbert, Susan R; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Išgum, Ivana|info:eu-repo/dai/nl/31484984X; Jukema, J Wouter; Kähönen, Mika; Kardia, Sharon L R; Kral, Brian G; Launer, Lenore J; Massaro, Joseph; Mehran, Roxana; Mitchell, Braxton D; Mosley, Thomas H; de Mutsert, Renée; Newman, Anne B; Nguyen, Khanh-Dung; North, Kari E; O'Connell, Jeffrey R; Oudkerk, Matthijs; Pankow, James S; Peloso, Gina M; Post, Wendy; Province, Michael A; Raffield, Laura M; Raitakari, Olli T; Reilly, Dermot F; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D; Teumer, Alexander; Trompet, Stella; Turner, Stephen T; Uitterlinden, André G; Vaidya, Dhananjay; van der Lugt, Aad; Völker, Uwe; Wardlaw, Joanna M; Wassel, Christina L; Weiss, Stefan; Wojczynski, Mary K; Becker, Diane M; Becker, Lewis C; Boerwinkle, Eric; Bowden, Donald W; Deary, Ian J; Dehghan, Abbas; Felix, Stephan B; Gudnason, Vilmundur; Lehtimäki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O; Psaty, Bruce M; Rader, Daniel J; Rotter, Jerome I; Wilson, James G; van Duijn, Cornelia M; Völzke, Henry; Kathiresan, Sekar; Peyser, Patricia A; O'Donnell, Christopher J

    2016-01-01

    BACKGROUND: -The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the

  6. Subclinical Measures of Atherosclerosis: Genetics and Cardiovascular Risk Prediction

    NARCIS (Netherlands)

    M. Kavousi (Maryam)

    2013-01-01

    markdownabstract__Abstract__ Atherosclerosis is a chronic, progressive, systematic condition with a long asymptomatic phase. Atherosclerosis develops gradually as a subclinical condition over the life course and eventually becomes clinically apparent as ischemic heart disease,

  7. Oral microbiota in patients with atherosclerosis

    DEFF Research Database (Denmark)

    Fåk, Frida; Tremaroli, Valentina; Bergström, Göran

    2015-01-01

    to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. METHODS: To elucidate whether the oral microbiota composition differed between......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...

  8. Macrophages, Dendritic Cells, and Regression of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jonathan E. Feig

    2012-07-01

    Full Text Available Atherosclerosis is the number one cause of death in the Western world. It results from the interaction between modified lipoproteins and monocyte-derived cells such as macrophages, dendritic cells, T cells, and other cellular elements of the arterial wall. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, that protrude into the arterial lumen. Ultimately, plaque rupture and thrombosis can occur leading to the clinical complications of myocardial infarction or stroke. Although each of the cell types plays roles in the pathogenesis of atherosclerosis, in this review, the focus will be primarily on the monocyte derived cells- macrophages and dendritic cells. The roles of these cell types in atherogenesis will be highlighted. Finally, the mechanisms of atherosclerosis regression as it relates to these cells will be discussed.

  9. Myocardin: A novel player in atherosclerosis.

    Science.gov (United States)

    Xia, Xiao-Dan; Zhou, Zhen; Yu, Xiao-Hua; Zheng, Xi-Long; Tang, Chao-Ke

    2017-02-01

    Myocardin (MYOCD) the most important coactivator of serum response factor (SRF), plays a critical role specifically in the development of cardiac myocytes and vascular smooth muscle cells (VSMCs). Binding of Myocardin to the SRF on the CArG box-containing target genes can transcriptionally activate a variety of downstream muscle-specific genes, such as Sm22α, Acta2, Myh11, and several other signaling pathways. Myocardin expression represents a contractile and differentiated SMC phenotype. Loss of Myocardin, however, represents a synthetic and dedifferentiated phenotype, a hallmark in atherosclerosis. Growing evidence shows that Myocardin is involved in lipid metabolism and vascular inflammation, the primary pathogenesis of atherosclerosis. Moreover, Myocardin expression level is altered in atherosclerotic patients and animal models, suggesting more extensive and important roles for Myocardin in atherosclerosis. In the current review, we summarized recent progress on the regulation and signaling of Myocardin, and highlighted its impacts on atherosclerotic disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Development of an animal model of selective coronary atherosclerosis

    NARCIS (Netherlands)

    Mihaylov, D; van Luyn, MJA; Rakhorst, G

    Background Atherosclerosis causes over 40% of all deaths in the USA and Western Europe. Although several hypotheses have been proposed, the etiology and pathogenesis of the atherosclerosis remain unknown. Objective To develop a model of selective coronary atherosclerosis in pigs. Design An animal

  11. Individual pathogens, pathogen burden, and markers of subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis

    Science.gov (United States)

    Szklo, Moyses; Ding, Jingzhong; Tsai, Michael Y.; Cushman, Mary; Polak, Joseph F.; Lima, João; Barr, R. Graham; Sharrett, A. Richey

    2009-01-01

    We examined the cross-sectional relationships of subclinical atherosclerosis – expressed by carotid intimal–medial thickness and coronary calcification – with antibodies to Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex virus, hepatitis A virus, and pathogen burden (number of positive pathogens). A random sample of 1056 individuals chosen from 5030 Multi-Ethnic Study of Atherosclerosis cohort participants were included. After multiple adjustment, no associations were found between atherosclerosis measures and either individual pathogens or pathogen burden. Interactions with inflammatory and endothelial function markers, demographic factors, BMI, high-density lipoprotein, diabetes, and smoking were also explored. The only interaction that was large, qualitative, statistically significant (P subclinical atherosclerosis. However, the study’s limitations, which include its cross-sectional design and insufficient statistical power, suggest that inferences from its findings should be made cautiously. PMID:19444130

  12. On epigenetic regulation in atherosclerosis pathology

    NARCIS (Netherlands)

    Wierda, Rutger Jeen

    2015-01-01

    Atherosclerosis is one of the primary causes of cardiovascular disease; the number one cause of death in the western society. Atherosclerotic plaque formation is a dynamic multi-cellular process where regulation of different genes essentially determines the activity of the different cell types

  13. Inherited disorders of HDL metabolism and atherosclerosis

    NARCIS (Netherlands)

    Hovingh, G Kees; de Groot, E.P.; van der Steeg, Wim; Boekholdt, S Matthijs; Hutten, Barbara A; Kuivenhoven, J.A.; Kastelein, John J P

    PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

  14. Effects of apolipoprotein M in uremic atherosclerosis

    DEFF Research Database (Denmark)

    Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

    2017-01-01

    BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...

  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

  16. Cyanotic congenital heart disease and atherosclerosis

    DEFF Research Database (Denmark)

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas

    2017-01-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether...

  17. Cytokines and Immune Responses in Murine Atherosclerosis

    NARCIS (Netherlands)

    Kusters, Pascal J. H.; Lutgens, Esther

    2015-01-01

    Atherosclerosis is an inflammatory disease of the vessel wall characterized by activation of the innate immune system, with macrophages as the main players, as well as the adaptive immune system, characterized by a Th1-dominant immune response. Cytokines play a major role in the initiation and

  18. Metabolic syndrome: the danger signal in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Patrick Mathieu

    2006-09-01

    Full Text Available Patrick Mathieu1, Philippe Pibarot2, Jean-Pierre Després31Department of Surgery, Centre de Recherche de l’Hôpital Laval/Institut de Cardiologie de Québec, Québec, Canada; 2Department of Medicine, Centre de Recherche de l’Hôpital Laval/Institut de Cardiologie de Québec, Québec, Canada; 3Department of Social and Preventive Medicine, Centre de Recherche de l’Hôpital Laval/Institut de Cardiologie de Québec, Québec, CanadaAbstract: Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipidderived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments. Keywords: atherosclerosis, inflammation, metabolic syndrome, innate immune system, danger signal theory

  19. Role of gut microbiota in atherosclerosis

    DEFF Research Database (Denmark)

    Jonsson, Annika Lindskog; Bäckhed, Gert Fredrik

    2017-01-01

    describe three pathways by which microbiota might affect atherogenesis. First, local or distant infections might cause a harmful inflammatory response that aggravates plaque development or triggers plaque rupture. Second, metabolism of cholesterol and lipids by gut microbiota can affect the development...... of atherosclerotic plaques. Third, diet and specific components that are metabolized by gut microbiota can have various effects on atherosclerosis; for example, dietary fibre is beneficial, whereas the bacterial metabolite trimethylamine-N-oxide is considered harmful. Although specific bacterial taxa have been......Infections have been linked to the development of cardiovascular disease and atherosclerosis. Findings from the past decade have identified microbial ecosystems residing in different habitats of the human body that contribute to metabolic and cardiovascular-related disorders. In this Review, we...

  20. 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.

  1. Coronary atherosclerosis: Significance of autophagic armour.

    Science.gov (United States)

    Arora, Mansi; Kaul, Deepak

    2012-09-26

    Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.

  2. THE GEOGRAPHIC PATHOLOGY OF CORONARY ATHEROSCLEROSIS.

    Science.gov (United States)

    SCOTT, R F; DAOUD, A S; LEE, K T

    1964-02-08

    The purpose of these studies was to find large groups with significantly less coronary atherosclerosis than New Yorkers and to investigate the possible reasons for these differences. Direct comparison of hearts and measurements of coronary artery wall thickness, autopsy series, and clinical diagnoses of outpatients and hospital admissions revealed that the amount of coronary atherosclerosis and the number of myocardial infarcts is significantly less in East and West Africans compared to New Yorkers matched for age and sex. The factors producing these differences are apparently operative in childhood. East Africans were found to have a shorter blood clot-lysis time, fewer venous (and arterial) thromboemboli and lower serum lipid levels, with a lower relative percentage of serum linoleates, than age-matched New Yorkers.

  3. 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.

  4. The role of dysfunctional HDL in atherosclerosis.

    Science.gov (United States)

    Navab, Mohamad; Reddy, Srinivasa T; Van Lenten, Brian J; Anantharamaiah, G M; Fogelman, Alan M

    2009-04-01

    This review focuses on HDL function in modulating LDL oxidation and LDL-induced inflammation. Dysfunctional HDL has been identified in animal models and humans with chronic inflammatory diseases including atherosclerosis. The loss of antiinflammatory function correlated with a loss of function in reverse cholesterol transport. In animal models and perhaps in humans, dysfunctional HDL can be improved by apoA-I mimetic peptides that bind oxidized lipids with high affinity.

  5. The role of dysfunctional HDL in atherosclerosis

    OpenAIRE

    Navab, Mohamad; Reddy, Srinivasa T.; Van Lenten, Brian J.; Anantharamaiah, G. M.; Fogelman, Alan M.

    2009-01-01

    This review focuses on HDL function in modulating LDL oxidation and LDL-induced inflammation. Dysfunctional HDL has been identified in animal models and humans with chronic inflammatory diseases including atherosclerosis. The loss of antiinflammatory function correlated with a loss of function in reverse cholesterol transport. In animal models and perhaps in humans, dysfunctional HDL can be improved by apoA-I mimetic peptides that bind oxidized lipids with high affinity.

  6. [Enterosorbents in the treatment of atherosclerosis].

    Science.gov (United States)

    Piskun, R P; Pentiuk, A A; Serkova, V K; Polesia, T L; Savitskaia, E A

    1998-01-01

    The article lists, characterizes, and discusses the mechanism of the action of endosorbents possessing hypocholesteremic and hypolipidemic effects. Among them are natural endosorbents--food fibers (cellulose, hemicellulose, pectins, gum, mucus, lignin and chitin compounds, etc.); artificial specific affinin and nonspecific carbonic enterosorbents (carbonitrate family, granulated, fibrous), as well as silica (aerosil, polysorb). The effectiveness and pathogenetic expediency of correcting disorders of lipid metabolism in atherosclerosis with enterosorbents is substantiated.

  7. Subclinical atherosclerosis and subsequent cognitive function.

    Science.gov (United States)

    Rossetti, Heidi C; Weiner, Myron; Hynan, Linda S; Cullum, C Munro; Khera, Amit; Lacritz, Laura H

    2015-07-01

    To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8-65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥ .052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥ .455). In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    Alique, Matilde; Luna, Carlos; Carracedo, Julia; Ramírez, Rafael

    2015-01-01

    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. PMID:26637360

  11. The Role of Cytokines in the Development of Atherosclerosis

    Science.gov (United States)

    Fatkhullina, A. R.; Peshkova, I. O.

    2017-01-01

    Atherosclerosis contributes to the development of many cardiovascular diseases, which remain the leading cause of death in developed countries. Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. It is caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a key factor at all stages of atherosclerosis progression. Cells involved in pathogenesis of atherosclerosis were shown to be activated by soluble factors, cytokines that strongly influence the disease development. Pro-inflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. In this review, we discuss the latest findings on the role of cytokines in the development and progression of atherosclerosis. PMID:27914461

  12. The role of the vascular dendritic cell network in atherosclerosis

    Science.gov (United States)

    Alberts-Grill, Noah; Denning, Timothy L.; Rezvan, Amir

    2013-01-01

    A complex role has been described for dendritic cells (DCs) in the potentiation and control of vascular inflammation and atherosclerosis. Resident vascular DCs are found in the intima of atherosclerosis-prone vascular regions exposed to disturbed blood flow patterns. Several phenotypically and functionally distinct vascular DC subsets have been described. The functional heterogeneity of these cells and their contributions to vascular homeostasis, inflammation, and atherosclerosis are only recently beginning to emerge. Here, we review the available literature, characterizing the origin and function of known vascular DC subsets and their important role contributing to the balance of immune activation and immune tolerance governing vascular homeostasis under healthy conditions. We then discuss how homeostatic DC functions are disrupted during atherogenesis, leading to atherosclerosis. The effectiveness of DC-based “atherosclerosis vaccine” therapies in the treatment of atherosclerosis is also reviewed. We further provide suggestions for distinguishing DCs from macrophages and discuss important future directions for the field. PMID:23552284

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    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......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...... (p atherosclerosis in the abdominal aorta in WHHL rabbits....

  14. 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.

  15. Atherosclerosis and incident depression in late life.

    Science.gov (United States)

    Newson, Rachel S; Hek, Karin; Luijendijk, Hendrika J; Hofman, Albert; Witteman, Jacqueline C M; Tiemeier, Henning

    2010-11-01

    Depression is a prominent concern for older adults; therefore, it is important to identify causal mechanisms so that prevention and treatment strategies can be developed. The vascular depression hypothesis proposes that vascular factors precede the onset of depression in older adults. However, although cross-sectional associations have been established, owing to a lack of objective assessments and longitudinal data, the validity and temporal nature of this relationship is unclear. To examine whether atherosclerosis, an asymptomatic subclinical indicator of vascular burden, increases the risk of developing depression in older adults. Prospective, population-based study. Set within the Rotterdam study, participants were assessed on objective measures of generalized atherosclerosis at baseline (1997-1999) and followed up for an average of 6 years for incident depression. The baseline sample consisted of 3564 participants (56% female) with a mean age of 72 years who initially did not have depression or dementia. Depression was categorized into symptoms or syndromes and assessed in a multidimensional manner from physician and mental health specialist reports, pharmacy records (antidepressant usage), a clinical interview, and self-report. During 21 083 person-years, 429 incidents of depressive symptoms and 197 incidents of depressive syndromes occurred. Individual atherosclerotic measures and a composite measure were not predictive of incident depressive symptoms (composite measure hazard ratio, 0.93; 95% confidence interval, 0.83-1.05) or incident depressive syndromes (composite measure hazard ratio, 0.97; 95% confidence interval, 0.81-1.16). An a priori power analysis indicated a sufficient sample size (α = .05; 0.95 power). Atherosclerosis does not appear to increase the risk of incident depression in older adults. These findings do not support the vascular depression hypothesis and, alternatively, taking findings from prior studies into account, suggest either that

  16. [Cerebral infarctions in vertebrobasilar artery atherosclerosis].

    Science.gov (United States)

    Anufriev, P L; Evdokimenko, A N; Gulevskaya, T S

    2018-01-01

    to obtain more specific information on the morphology and pathogenesis of cerebral infarctions occurring in vertebrobasilar artery (VBA) atherosclerosis. Macro- and microscopic investigations of the brain, its arterial system, and heart were conducted in 69 autopsy cases with infarctions located in the vertebrobasilar system (VBS) in atherosclerosis. 69 cases were found to have 206 VBA infarctions of various extent and locations. The detected infarctions were single and multiple in 27 and 42 cases, respectively. The detected infarctions included extensive (n=7), large (n=9), medium (n=63), small deep (lacunar) (n=97), and small superficial (n=30). The brain stem showed lacunar infarctions most frequently (76% of the infarctions at this site). Medium and small infarctions were identified at the same frequency in the cerebral hemispheres and cerebellum. The occurrence of 94% of the extensive and large infarctions was ascertained to be pathogenetically associated with atherothrombotic occlusion of the intracranial arteries in the VBS. 76% of the small infarctions occurred through the mechanism of cerebral vascular insufficiency in tandem atherostenosis of VBAs in conjunction with an additional decrease in cerebral blood flow under the influence of an extracerebral factor (coronary heart disease). Medium infarctions were approximately equifrequently due to the two aforementioned causes and, in some cases, to cardiogenic thromboembolism of VBAs. Infarctions were multiple in most cases; while recent large atherothrombotic infarctions were frequently concurrent with small organized infarctions resulting from tandem atherostenosis of VBAs. This investigation could establish the relationship between the site, extent, and pathogenetic factors of infarctions in the VBA bed in atherosclerosis, as well as the prognostic value of small infarctions as predictors for severe ischemic stroke.

  17. Epidemiological aspects of atherosclerosis in patients treated for acute atherothrombosis of extremity arteries

    National Research Council Canada - National Science Library

    Rustempasic, Nedzad; Totic, Dragan; Djedovic, Muhamed; Rustempasic, Medzida; Malesic, Nada

    2014-01-01

    Risk factors for development of extremity artery atherosclerosis are the same as for coronary and cerebrovascular atherosclerosis namely, diabetes mellitus, hyperlipidemia, arterial hypertension, age and smoking...

  18. Probiotics and atherosclerosis – a new challenge?

    Directory of Open Access Journals (Sweden)

    Chan Yee Kwan

    2012-06-01

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

  19. Requirement for CD154 in the progression of atherosclerosis

    NARCIS (Netherlands)

    Lutgens, E.; Gorelik, L.; Daemen, M. J.; de Muinck, E. D.; Grewal, I. S.; Koteliansky, V. E.; Flavell, R. A.

    1999-01-01

    Atherosclerosis is a systemic disease of the large arteries, and activation of inflammatory pathways is important in its pathogenesis. Increasing evidence supports the importance of CD40-CD154 interactions in atherosclerosis, interactions originally known to be essential in major immune reactions

  20. Apolipoprotein E and carotid artery atherosclerosis - The Rotterdam study

    NARCIS (Netherlands)

    Slooter, AJC; Bots, ML; Havekes, LM; del Sol, AI; Cruts, M; Grobbee, DE; Hofman, A; Van Broeckhoven, C; Witteman, JCM; van Duijn, CM

    Background and Purpose-Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery

  1. Endogenous hormones and carotid atherosclerosis in elderly men

    NARCIS (Netherlands)

    A.W. van den Beld (Annewieke); M.L. Bots (Michiel); J.A.M.J.L. Janssen (Joseph); H.A.P. Pols (Huib); S.W.J. Lamberts (Steven); D.E. Grobbee (Diederick)

    2003-01-01

    textabstractThe aging process is characterized by a number of gradual changes in circulating hormone concentrations as well as a gradual increase in the degree of atherosclerosis. The authors studied whether serum hormone levels are related to atherosclerosis of the carotid

  2. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C.; Bielak, Lawrence F.; Cox, Amanda J.; Dorr, Marcus; Feitosa, Mary F.; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A.; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikainen, Leo-Pekka; Marioni, Riccardo E.; Schminke, Ulf; Stitziel, Nathan O.; Tada, Hayato; van Setten, Jessica; Smith, Albert V.; Vojinovic, Dina; Yanek, Lisa R.; Yao, Jie; Yerges-Armstrong, Laura M.; Amin, Najaf; Baber, Usman; Borecki, Ingrid B.; Carr, J. Jeffrey; Chen, Yii-Der Ida; Cupples, L. Adrienne; de Jong, Pim A.; de Koning, Harry; de Vos, Bob D.; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H.; Goodarzi, Mark O.; Harris, Tamara B.; Heckbert, Susan R.; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Isgum, Ivana; Jukema, J. Wouter; Kahonen, Mika; Kardia, Sharon L. R.; Kral, Brian G.; Launer, Lenore J.; Massaro, Joe; Mehran, Roxana; Mitchell, Braxton D.; Jr, Thomas H. Mosley; de Mutsert, Renee; Newman, Anne B.; Nguyen, Khanh-dung; North, Kari E.; O'Connell, Jeffrey R.; Oudkerk, Matthijs; Pankow, James S.; Peloso, Gina M.; Post, Wendy; Province, Michael A.; Raffield, Laura M.; Raitakari, Olli T.; Reilly, Dermot F.; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D.; Teumer, Alexander; Trompet, Stella; Turner, Stephen T.; Uitterlinden, Andre G.; Vaidya, Dhananjay; van der Lugt, Aad; Volker, Uwe; Wardlaw, Joanna M.; Wassel, Christina L.; Weiss, Stefan; Wojczynski, Mary K.; Becker, Diane M.; Becker, Lewis C.; Boerwinkle, Eric; Bowden, Donald W.; Deary, Ian J.; Dehghan, Abbas; Felix, Stephan B.; Gudnason, Vilmundur; Lehtimaki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O.; Psaty, Bruce M.; Rader, Daniel J.; Rotter, Jerome I.; Wilson, James G.; van Duijn, Cornelia M.; Volzke, Henry; Kathiresan, Sekar; Peyser, Patricia A.; O'Donnell, Christopher J.

    2016-01-01

    Background-The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of

  3. Is there an association between coronary atherosclerosis and ...

    African Journals Online (AJOL)

    Background: Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades. If atherosclerosis and ...

  4. Imaging of atherosclerosis: study design and cardiovascular risk prediction

    NARCIS (Netherlands)

    Peters, S.A.E.|info:eu-repo/dai/nl/341652326

    2012-01-01

    Cardiovascular disease is still the leading cause of morbidity and mortality worldwide.1 The majority of cardiovascular disease events is caused by atherosclerosis. Atherosclerosis is a slow and progressive disease of the arterial wall that is on the pathway between the effects of exposure to risk

  5. Apolipoprotein E genotype, atherosclerosis, and cognitive decline : The Rotterdam study

    NARCIS (Netherlands)

    Slooter, A.J.C.; Duijn, C.M. van; Bots, M.L.; Ott, A.; Breteler, M.B.; Voecht, J. de; Wehnert, A.; Knijff, P. de; Havekes, L.M.; Grobbee, D.E.; Broeckhoven, C. van; Hofman, A.

    1998-01-01

    The apolipoprotein E4 allele (APOEε4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOEε4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at

  6. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

    NARCIS (Netherlands)

    Nagareddy, Prabhakara R.; Murphy, Andrew J.; Stirzaker, Roslynn A.; Hu, Yunying; Yu, Shiquing; Miller, Rachel G.; Ramkhelawon, Bhama; Distel, Emilie; Westerterp, Marit; Huang, Li-Shin; Schmidt, Ann Marie; Orchard, Trevor J.; Fisher, Edward A.; Tall, Alan R.; Goldberg, Ira J.

    2013-01-01

    Diabetes is a major risk factor for atherosclerosis. Although atherosclerosis is initiated by deposition of cholesterol-rich lipoproteins in the artery wall, the entry of inflammatory leukocytes into lesions fuels disease progression and impairs resolution. We show that diabetic mice have increased

  7. Accelerated atherosclerosis in SLE: mechanisms and prevention approaches

    Science.gov (United States)

    Wilhelm, Ashley J.; Major, Amy S.

    2014-01-01

    Summary Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by increased serum autoantibody levels and tissue damage. With improved diagnosis and more effective treatment of the resultant kidney disease, accelerated atherosclerosis has become a major cause of morbidity in patients suffering from SLE. Although the exact mechanisms for SLE-accelerated atherosclerosis are unknown, multiple factors have been established as potential players in this process. Among these potential players are dysregulation of T and B cell populations and increased circulating levels of inflammatory cytokines. In addition, SLE patients exhibit a proatherogenic lipid profile characterized by low HDL and high LDL and triglycerides. Recent therapeutic approaches have focused on targeting B cells, the producers of autoantibodies, but most studies do not consider the effects of these treatments on atherosclerosis. Evidence suggests that T cells play a major role in SLE-accelerated atherosclerosis. Therefore, therapies targeted at T cells may also prove invaluable in treating SLE and atherosclerosis. PMID:24672580

  8. Genetic Basis of Atherosclerosis: Insights from Mice and Humans

    Science.gov (United States)

    Stylianou, Ioannis M.; Bauer, Robert C.; Reilly, Muredach P.; Rader, Daniel J.

    2012-01-01

    Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have in part been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease (CAD). Here we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human CAD. Furthermore, we discuss in greater detail some of these novel human CAD loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches. PMID:22267839

  9. Quantum dot mediated imaging of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Jayagopal, Ashwath; Haselton, Frederick R [Department of Biomedical Engineering, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Su Yanru; Blakemore, John L; Linton, MacRae F; Fazio, Sergio [Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)], E-mail: rick.haselton@vanderbilt.edu

    2009-04-22

    The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE{sup -/-} mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

  10. 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.

  11. Environmental factors influencing the development of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Andrzej Brodziak

    2013-12-01

    Full Text Available The aim of the paper is to present an overview of recent findings on the environmental and behavioral factors influencing the development of atherosclerosis. The authors primarily concentrated on deliberations of possibile main causes of the damage of the endothelium. At the same time the following pathogenic mechanisms as cellular dysfunction, inflammation and coagulation disorders have been enumerated. The links between the state of the vascular endothelium and life style have been emphasized. It is also important to note that the primary causes of the endothelial damage should be traced as originally suggested many years ago viewing such factors as anger, hostility, aggression, impulsiveness and depression but with a new approach. The authors supplement the comments, on the environmental factors influencing the development of atherosclerosis, with basic data on family predisposition to the development of this disease. They highlight that current genetic research have not determined genes responsible for atheroscelosis. According to the authors the considerations and conclusions presented in this overview are important for the educational purposes related to the most frequent disease process resulting in many diseases in medical disciplines.

  12. Quantum dot mediated imaging of atherosclerosis

    Science.gov (United States)

    Jayagopal, Ashwath; Su, Yan Ru; Blakemore, John L.; Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

    2009-04-01

    The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE-/- mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

  13. 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....

  14. Antidepressant Use and Subclinical Measures of Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Camacho, Álvaro; McClelland, Robyn L; Delaney, Joseph A; Allison, Matthew A; Psaty, Bruce M; Rifkin, Dena E; Rapp, Stephen R; Szklo, Moyses; Stein, Murray B; Criqui, Michael H

    2016-08-01

    Antidepressants are commonly prescribed medications used in primary care. The cardiovascular safety profile of antidepressant medications, in terms of subclinical atherosclerosis, is underexamined. A total of 6814 participants in the Multi-Ethnic Study of Atherosclerosis were examined. At baseline, the mean age was 62 years with 4 race/ethnic groups represented: European Americans (38%), Hispanic Americans (23%), African Americans (28%), and Chinese Americans (11%). Antidepressants were subgrouped as serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and "other" (bupropion, nefazodone, trazodone, mirtazapine). After adjusting for potential confounders, we estimated the association between antidepressant use and the following measures of subclinical atherosclerosis: coronary artery calcium (CAC), the ankle-brachial index, and carotid intima-media thickness, both cross-sectionally and prospectively. A total of 324 participants were exposed to SSRIs, 88 to TCAs, 41 to SNRIs, and 123 to other antidepressants. For CAC incidence, the fully adjusted longitudinal analyses revealed no consistent associations with SSRIs (relative risk [RR], 0.99; 95% confidence interval [CI], 0.71-1.37), SNRIs (RR, 0.49; 95% CI, 0.13-1.86), TCAs (RR, 0.94; 95% CI, 0.50-1.77), other antidepressant (RR, 0.87; 95% CI, 0.73-1.03) exposure, and subclinical disease. Similar null results were obtained in the cross-sectional and longitudinal exposure to antidepressants with changes in baseline CAC greater than 0, ankle-brachial index, and carotid intima-media thickness. The results of the current study do not support an association between antidepressants and subclinical atherosclerosis.

  15. HDL signaling and protection against coronary artery atherosclerosis in mice.

    Science.gov (United States)

    Trigatti, Bernardo L; Fuller, Mark

    2016-03-01

    Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke, important causes of morbidity and mortality across the globe. Abundant epidemiological studies demonstrate that high levels of high density lipoprotein (HDL) are associated with reduced risk of atherosclerosis and preclinical, animal model studies demonstrate that this association is causative. Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics. Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall. These signaling responses require the HDL receptor, scavenger receptor class B type 1 (SR-B1), an adaptor protein (PDZK1) that binds to the cytosolic C terminus of SR-B1, Akt1 activation and (at least in endothelial cells) activation of endothelial NO synthase (eNOS). Mouse models of atherosclerosis, exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice (apoE or LDLR KO) develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis. On the other hand, inactivation of each of the components of HDL signaling (above) in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease. © 2016 by the Journal of Biomedical Research. All rights reserved.

  16. Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

    Directory of Open Access Journals (Sweden)

    Luciano Alves Matias da Silveira

    Full Text Available Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. Method: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. Results: Microscopic atherosclerosis was higher in young subjects (early injury and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. Conclusion: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.

  17. Connective tissue diseases and noninvasive evaluation of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ardita G

    2014-06-01

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

  18. Nanotechnology, a new paradigm in atherosclerosis treatment.

    Science.gov (United States)

    Martín Giménez, Virna M; Ruiz-Roso, María Belén; Camargo, Alejandra Beatriz; Kassuha, Diego; Manucha, Walter

    Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. [Cholesterol and atherosclerosis. Historical considerations and treatment].

    Science.gov (United States)

    Zárate, Arturo; Manuel-Apolinar, Leticia; Basurto, Lourdes; De la Chesnaye, Elsa; Saldívar, Iván

    2016-01-01

    Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming «cholesterol»; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease. Copyright © 2016. Published by Masson Doyma México S.A.

  20. 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.

  1. Serum lipopolysaccharide-binding protein as a marker of atherosclerosis.

    Science.gov (United States)

    Serrano, Marta; Moreno-Navarrete, José María; Puig, Josep; Moreno, María; Guerra, Ester; Ortega, Francisco; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel

    2013-10-01

    Recently, serum lipopolysaccharide-binding protein (LBP) has been closely associated with coronary artery disease. Here, we aimed to investigate the possible relationship between serum LBP and markers of atherosclerosis. Serum LBP and carotid intima media thickness (C-IMT) were measured in 332 subjects (101 men and 231 women) who were recruited from an ongoing multicenter project. Serum LBP was significantly associated with obesity [BMI, fat mass and waist circumference (r > 0.38, p atherosclerosis marker, reveals serum LBP as a putative factor related to atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  3. Lipoprotein (a) and carotid atherosclerosis in young patients with stroke.

    Science.gov (United States)

    Nasr, Nathalie; Ruidavets, Jean Bernard; Farghali, Ahmed; Guidolin, Brigitte; Perret, Bertrand; Larrue, Vincent

    2011-12-01

    Elevated lipoprotein (a) concentration is associated with carotid atherosclerosis in middle-aged and older patients with ischemic stroke. This association has not been explored in young patients with stroke. A retrospective analysis of data from patients aged 16 to 54 years consecutively treated for acute ischemic stroke in a tertiary stroke unit during 4.5 years was performed. We graded carotid atherosclerosis using carotid duplex as: no atherosclerosis (A); plaque without stenosis (B); or stenosis≥50% (C). One hundred ninety-six patients were included (male/female: 119/77; mean age±SD: 44.3±8.6 years): 115 in Group A; 67 in Group B; and 14 in Group C. Multivariate analysis using polynomial logistic regression showed a graded association of lipoprotein (a) plasma concentration with carotid atherosclerosis (Patherosclerosis in young adults with ischemic stroke. This association was strong, graded, and independent of traditional risk factors including cholesterol.

  4. Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis

    NARCIS (Netherlands)

    van der Valk, Fleur M; Schulte, Dominik M; Meiler, Svenja; Tang, Jun; Zheng, Kang He; Van den Bossche, Jan; Seijkens, Tom; Laudes, Matthias; de Winther, Menno; Lutgens, Esther; Alaarg, Amr|info:eu-repo/dai/nl/370549465; Metselaar, Josbert M|info:eu-repo/dai/nl/244207690; Dallinga-Thie, Geesje M; Mulder, Willem J M; Stroes, Erik S G; Hamers, Anouk A J

    2016-01-01

    Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we

  5. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

    NARCIS (Netherlands)

    Kim, Yongtae; Lobatto, Mark E.; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J.; Sanchez-Gaytan, Brenda L.; Fay, Francois; Senders, Max L.; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E.; Stroes, Erik S. G.; Ma, Mingming; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.; Langer, Robert

    2014-01-01

    Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease.

  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. 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.

  8. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1......) in the endothelia of Apoe(-/-) mice (Irs1/Apoe(-/-)) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE(-/-) mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

  9. (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....

  10. What Are the Signs and Symptoms of Atherosclerosis?

    Science.gov (United States)

    ... artery disease ), you may have symptoms of a stroke. These symptoms may include: Sudden weakness Paralysis (an inability to ... avoid serious problems, such as heart attack and stroke . Follow your treatment plan ... Issues and Support Having an atherosclerosis-related ...

  11. Increased atherosclerosis in mice with increased vascular biglycan content.

    Science.gov (United States)

    Thompson, Joel C; Tang, Tao; Wilson, Patricia G; Yoder, Meghan H; Tannock, Lisa R

    2014-07-01

    The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development. Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4-12 weeks. LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content. Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development. Published by Elsevier Ireland Ltd.

  12. MicroRNA-33 in atherosclerosis etiology and pathophysiology.

    Science.gov (United States)

    Chen, Wu-Jun; Zhang, Min; Zhao, Guo-Jun; Fu, Yuchang; Zhang, Da-Wei; Zhu, Hai-Bo; Tang, Chao-Ke

    2013-04-01

    MicroRNAs are a group of endogenous, small non-coding RNA molecules that can induce translation repression of target genes within metazoan cells by specific base pairing with the mRNA of target genes. Recently, microRNA-33 has been discovered as a key regulator in the initiation and progression of atherosclerosis. This review highlights the impact of microRNA-33-mediated regulation in the major cardiometabolic risk factors of atherosclerosis including lipid metabolism (HDL biogenesis and cholesterol homeostasis, fatty acid, phospholipid and triglyceride, bile acids metabolism), inflammatory response, insulin signaling and glucose/energy homeostasis, cell cycle progression and proliferation, and myeloid cell differentiation. Understanding the etiology and pathophysiology of microRNA-33 in atherosclerosis may provide basic knowledge for the development of novel therapeutic targets for ameliorating atherosclerosis and cardiovascular disease. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Obstructive sleep apnea: an emerging risk factor for atherosclerosis

    National Research Council Canada - National Science Library

    Drager, Luciano F; Polotsky, Vsevolod Y; Lorenzi-Filho, Geraldo

    2011-01-01

    .... OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia...

  14. Accelerated atherosclerosis in patients with systemic autoimmune diseases

    NARCIS (Netherlands)

    De Leeuw, K.; Kallenberg, Cees; Bijl, Marc; Shoenfeld, Y.; Gershwin, M.E.; Shoenfeld, Y; Gershwin, ME

    2005-01-01

    Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis,

  15. HDL signaling and protection against coronary artery atherosclerosis in mice

    OpenAIRE

    Bernardo L Trigatti; Fuller, Mark

    2015-01-01

    Abstract Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke, important causes of morbidity and mortality across the globe. Abundant epidemiological studies demonstrate that high levels of high density lipoprotein (HDL) are associated with reduced risk of atherosclerosis and preclinical, animal model studies demonstrate that this association is causative. Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic a...

  16. Atherosclerosis, cholesterol, nutrition, and statins ? a critical review

    OpenAIRE

    Gebbers, Jan-Olaf

    2007-01-01

    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, especial...

  17. Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

    DEFF Research Database (Denmark)

    Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina

    2015-01-01

    diet (r(2)=0.33, Pinflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients...... with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta. CONCLUSIONS: (18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis....

  18. 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....

  19. The walking dead: macrophage inflammation and death in atherosclerosis.

    Science.gov (United States)

    Kavurma, Mary M; Rayner, Katey J; Karunakaran, Denuja

    2017-04-01

    To highlight recent studies that describe novel inflammatory and signaling mechanisms that regulate macrophage death in atherosclerosis. Macrophages contribute to all stages of atherosclerosis. The traditional dogma states that in homeostatic conditions, macrophages undergo apoptosis and are efficiently phagocytosed to be cleared by a process called efferocytosis. In advanced atherosclerosis, however, defective efferocytosis results in secondary necrosis of these uncleared apoptotic cells, which ultimately contributes to the formation of the characteristic necrotic core and the vulnerable plaque. Here, we outline the different types of lesional macrophage death: apoptosis, autophagic and the newly defined necroptosis (i.e. a type of programmed necrosis). Recent discoveries demonstrate that macrophage necroptosis directly contributes to necrotic core formation and plaque instability. Further, promoting the resolution of inflammation using preresolving mediators has been shown to enhance efferocytosis and decrease plaque vulnerability. Finally, the canonical 'don't eat me' signal CD47 has recently been described as playing an important role in atherosclerotic lesion progression by impairing efficient efferocytosis. Although we have made significant strides in improving our understanding of cell death and clearance mechanisms in atherosclerosis, there still remains unanswered questions as to how these pathways can be harnessed using therapeutics to promote lesion regression and disease stability. Improving our understanding of the mechanisms that regulate macrophage death in atherosclerosis, in particular apoptosis, necroptosis and efferocytosis, will provide novel therapeutic opportunities to resolve atherosclerosis and promote plaque stability.

  20. Onychomycosis is associated with subclinical atherosclerosis in patients with diabetes.

    Science.gov (United States)

    Onalan, Orhan; Adar, Adem; Keles, Hakan; Ertugrul, Goksen; Ozkan, Nurhayat; Aktas, Habibullah; Karakaya, Ekrem

    2015-01-01

    We aimed to investigate the association of toenail onychomycosis with subclinical atherosclerosis in patients with diabetes mellitus. Consecutive diabetic patients who were seen at our outpatient clinic were enrolled. The carotid intima-media thickness (CIMT) was assessed and toenail onychomycosis was diagnosed with microscopic evaluation. We investigated 127 patients with diabetes melltus type 2. Overall, the prevalence of toenail onychomycosis was 37.8 % (48 of 127). Of the 127 patients, 60 (47.2 %) had subclinical atherosclerosis (CIMT ≥ 1 mm). Prevalence of male gender (43.3 % vs. 22.4 %, p = 0.012) and onychomycosis (53.3 % vs. 23.9 %, p = 0.001) was significantly higher in patients with subclinical atherosclerosis. Among biochemical parameters, low-density lipoprotein (122 ± 38 mg/dL vs. 108 ± 36 mg/dL, p = 0.039) and glycosylated hemoglobin levels (median 8.4 %, IQR: 2.1 % vs. median 7.5 %, IQR: 1.6 %, p = 0.002) were significantly higher in patients with subclinical atherosclerosis. Study groups were similar with respect to all other demographic, clinical, and laboratory parameters. After adjustment for all potential confounders, the presence of onychomycosis was independently associated with subclinical atherosclerosis (OR 2.77, 95 % CI 1.16 to 6.30) in multivariate logistic regression analysis. Presence of onychomycosis in patients with diabetes is associated with subclinical atherosclerosis. Onychomycosis may be a marker of atherosclerotic arterial involvement.

  1. Assessment of subclinical atherosclerosis using contrast-enhanced ultrasound.

    Science.gov (United States)

    van den Oord, Stijn C H; ten Kate, Gerrit L; Akkus, Zeynettin; Renaud, Guillaume; Sijbrands, Eric J G; ten Cate, Folkert J; van der Lugt, Aad; Bosch, Johan G; de Jong, Nico; van der Steen, Antonius F W; Schinkel, Arend F L

    2013-01-01

    The sensitivity of standard carotid ultrasound and colour Doppler for the detection of subclinical atherosclerotic plaques is suboptimal. The aim of this study is to assess whether contrast-enhanced ultrasound (CEUS) added to standard carotid ultrasound improves the detection of subclinical atherosclerosis. Carotid intima-media thickness (CIMT) measurement, standard carotid ultrasound including colour Doppler imaging, and CEUS were performed in 100 asymptomatic patients with one or more risk factors for atherosclerosis. CEUS was performed using intravenous administration of SonoVue™ contrast agent (Bracco S.p.A., Milan, Italy). CIMT, standard ultrasound, colour Doppler, and CEUS were reviewed by two independent observers. Standard ultrasound, colour Doppler, and CEUS were scored for the presence of atherosclerotic plaques. Subclinical atherosclerosis was diagnosed if patients had a CIMT above their age-corrected threshold value or if atherosclerotic plaques were present on standard carotid ultrasound clips or CEUS clips. McNemar's test was performed to compare between groups. Twenty-one patients (21%) had a thickened CIMT value and were considered to have subclinical atherosclerosis. Standard carotid ultrasound including colour Doppler demonstrated atherosclerotic plaques in 77 patients (77%). The addition of CEUS to the standard ultrasound protocol demonstrated atherosclerotic plaques in 88 patients (88%). The incorporation of CEUS into the standard carotid ultrasound protocol resulted in a significantly improved detection of patients with subclinical atherosclerosis (P subclinical atherosclerosis in the carotid arteries. Atherosclerotic plaques which were only detected with CEUS and not with standard carotid ultrasound and colour Doppler imaging were predominantly hypoechoic.

  2. Positive Expression of Human Cytomegalovirus Phosphoprotein 65 in Atherosclerosis

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    Zhe Wang

    2016-01-01

    Full Text Available Previous studies showed that human cytomegalovirus (HCMV is associated with atherosclerosis. However, local vascular atherosclerosis related HCMV infection and protein expression remain unclear. This study aimed to assess the relationship between HCMV infection and atherosclerosis. Formalin-fixed, paraffin-embedded peripheral artery specimens were obtained from 15 patients with atherosclerosis undergoing vascular surgery from 2008 to 2010 at Zhongnan Hospital, Wuhan University. Pathological analyses were carried out after hematoxylin and eosin (H&E and Masson trichrome staining. In situ hybridization and immunohistochemistry with two different monoclonal antibodies were employed to detect HCMV nucleic acids and proteins, respectively. H&E and Masson trichrome staining showed homogeneous extracellular matrix in femoral artery, while smooth muscle fibers were interlaced with collagen fibers; in carotid artery, inflammatory cell infiltration, foam cell vascular change, cholesterol crystals, and layered collagen fibers were observed. In situ hybridization showed no expression of HCMV nucleic acids in all 15 cases. Immunohistochemical staining for protein immediate-early protein (IE1 72 was negative in all cases, while phosphoprotein 65 (pp65 expression was detected in 14 cases. A high rate of positive pp65 signals was found in patients with atherosclerosis, suggesting that local HCMV infection may be associated with the pathogenesis of atherosclerosis. Further studies on this relationship are warranted.

  3. Positive Expression of Human Cytomegalovirus Phosphoprotein 65 in Atherosclerosis.

    Science.gov (United States)

    Wang, Zhe; Cai, Jun; Zhang, Mingming; Wang, Xiaojing; Chi, Hongjie; Feng, Haijun; Yang, Xinchun

    2016-01-01

    Previous studies showed that human cytomegalovirus (HCMV) is associated with atherosclerosis. However, local vascular atherosclerosis related HCMV infection and protein expression remain unclear. This study aimed to assess the relationship between HCMV infection and atherosclerosis. Formalin-fixed, paraffin-embedded peripheral artery specimens were obtained from 15 patients with atherosclerosis undergoing vascular surgery from 2008 to 2010 at Zhongnan Hospital, Wuhan University. Pathological analyses were carried out after hematoxylin and eosin (H&E) and Masson trichrome staining. In situ hybridization and immunohistochemistry with two different monoclonal antibodies were employed to detect HCMV nucleic acids and proteins, respectively. H&E and Masson trichrome staining showed homogeneous extracellular matrix in femoral artery, while smooth muscle fibers were interlaced with collagen fibers; in carotid artery, inflammatory cell infiltration, foam cell vascular change, cholesterol crystals, and layered collagen fibers were observed. In situ hybridization showed no expression of HCMV nucleic acids in all 15 cases. Immunohistochemical staining for protein immediate-early protein (IE1 72) was negative in all cases, while phosphoprotein 65 (pp65) expression was detected in 14 cases. A high rate of positive pp65 signals was found in patients with atherosclerosis, suggesting that local HCMV infection may be associated with the pathogenesis of atherosclerosis. Further studies on this relationship are warranted.

  4. Molecular genetics and gene expression in atherosclerosis.

    Science.gov (United States)

    Doevendans, P A; Jukema, W; Spiering, W; Defesche, J C; Kastelein, J J

    2001-01-01

    Although molecular cardiology is a relative young discipline, the impact of the new techniques on diagnosis and therapy in cardiovascular disease are extensive. Our insight into pathophysiological mechanisms is rapidly expanding and is changing our understanding of cardiovascular disease radically and irrevocably. Molecular cardiology has many different aspects. In this paper the importance of molecular cardiology and genetics for every day clinical practice are briefly outlined. It is expected that in the genetic predisposition for atherosclerotic disease multiple genes are involved (genetics). The role of only a minority of genes involved in the atherosclerotic process is known. Far less is known about particular gene-gene and gene-environment interactions. In some families disease can be explained mostly by a single, major gene (monogenic), of which the lipid disorder Familial Hypercholesterolemia is an example. In other cases, one or several variations in minor genes (multigenic) contribute to an atherosclerotic predisposition, for instance the lipoprotein lipase gene. Although mutations in this gene influence lipoprotein levels, disease development is predominantly depending on environmental influences. Recently several additional genetic risk factors were identified including elevated levels of lipoprotein (a) [Lp(a)], the DD genotype of angiotensin converting enzyme (ACE), and elevated levels of homocysteine. This illustrates the complexity of genetics in relation to atherosclerosis and the difficulty to assign predictive values to separate genetic risk factors. Furthermore, little attention has been given to protective genes thus far, explaining why some high risk patients are protected from vascular disease. Genetics based treatment or elimination of the genetic risk factor requires complete understanding of the pathogenic molecular basis. Once this requirement is fulfilled, disease management can be strived for, provided that adequate medical management

  5. Trajectories of Neighborhood Poverty and Associations With Subclinical Atherosclerosis and Associated Risk Factors: The Multi-Ethnic Study of Atherosclerosis

    OpenAIRE

    Murray, Emily T.; Diez Roux, Ana V.; Carnethon, Mercedes; Lutsey, Pamela L; Ni, Hanyu; O'Meara, Ellen S.

    2010-01-01

    The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980–2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors...

  6. Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

    Science.gov (United States)

    López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A.; Huaranga, Marco A. Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J.; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J. Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

    2017-01-01

    A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA. PMID:28059143

  7. Noninvasive Diagnostic Technique in Stenotic Coronary Atherosclerosis

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    A. Yu. Vasilyev

    2005-01-01

    Full Text Available Objective: to determine the sensitivity and specificity of combined stress echocardiography (EchoCG using dipyri-damole and dobutamine in diagnosing and defining the extent of stenotic coronary lesions in coronary heart disease (CHD in a group of critically ill patients who are unable to perform a physical exercise.Materials and methods: the study included 57 male patients with suspected acute coronary syndrome who underwent stress EchoCG using dipyridamole in high doses in combination with dobutamine, as well as coronary angiography.Results: stress EchoCG could bring up to the diagnostic criteria in all the patients, of whom 9 patients were found at coronary angiography to have no coronary lesion, 34 and 14 patients had one- and many-vessel lesions, respectively. The sensitivity and specificity of combined stress EchoCG were significantly higher than those of EchoCG used in the diagnosis of CHD.Conclusion: stress EchoCG using dipyridamole in combination with dobutamine is a highly informative safe noninvasive technique for diagnosing CHD, its helps to identify patients with atypical acute coronary syndrome and to form a group of patients to be subject to urgent coronarography and angiosurgical intervention. The pattern of segmental contractile disorders at the height of exercise during combined stress Echo-CG makes it possible to define the site of stenotic coronary atherosclerosis with 97.3% sensitivity and to diagnose many-vessel lesion with 100% sensitivity and 100%specificity.

  8. Endothelium Preserving Microwave Treatment for Atherosclerosis

    Science.gov (United States)

    Carl, James R. (Inventor); Arndt, G. Dickey (Inventor); Fink, Patrick W. (Inventor); Beer, N. Reginald (Inventor); Henry, Phillip D. (Inventor); Pacifico, Antonio (Inventor); Raffoul, George W. (Inventor)

    2001-01-01

    Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof. Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial layer and/or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 C. within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed directable or focussed heating preserves healthy sectors of the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed beam. A computer simulation predicts isothermic temperature profiles for the given conditions and may be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

  9. Chemical food composition: implications for atherosclerosis prevention.

    Science.gov (United States)

    Scherr, Carlos; Ribeiro, Jorge Pinto

    2011-01-01

    To compare the fatty acid and cholesterol content in food acquired in Brazil with the composition found in the most frequently used reference tables in the country. The fatty acid and cholesterol content in 41 food items frequently used in our country and the various directions to prepare them were reviewed by using specific methodology and the information was compared to the tables adopted by Unicamp and UNIFESP. According to Unicamp table, the cholesterol content found in parmesan cheese was 100.7 mg/100 g, while it was 68 mg/100 g in UNIFESP table, that is, a 48% (p cholesterol content 31% lower (94 mg/100 g vs. 123 mg/100 g, p cheese. For whole milk, we found a 52% difference regarding cholesterol content, while the difference for saturated fat ranged from 1.4 g/100 g in Unicamp table to 2.130 g/100 g in our study table (p cholesterol content formally analyzed and the content shown on commonly used tables, and this can compromise our recommendations on preventing atherosclerosis. One possible explanation for the differences would be the fact that the UNIFESP table is American in origin.

  10. 3-Nitrotyrosine Modified Proteins in Atherosclerosis

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    Leonor Thomson

    2015-01-01

    Full Text Available Cardiovascular disease is the leading cause of premature death worldwide, and atherosclerosis is the main contributor. Lipid-laden macrophages, known as foam cells, accumulate in the subendothelial space of the lesion area and contribute to consolidate a chronic inflammatory environment where oxygen and nitrogen derived oxidants are released. Oxidatively modified lipids and proteins are present both in plasma as well as atherosclerotic lesions. A relevant oxidative posttranslational protein modification is the addition of a nitro group to the hydroxyphenyl ring of tyrosine residues, mediated by nitric oxide derived oxidants. Nitrotyrosine modified proteins were found in the lesion and also in plasma from atherosclerotic patients. Despite the fact of the low yield of nitration, immunogenic, proatherogenic, and prothrombotic properties acquired by 3-nitrotyrosine modified proteins are in agreement with epidemiological studies showing a significant correlation between the level of nitration found in plasma proteins and the prevalence of cardiovascular disease, supporting the usefulness of this biomarker to predict the outcome and to take appropriate therapeutic decisions in atherosclerotic disease.

  11. Research Advances of Atherosclerosis in Translational Medicine

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    Zhuo-xin YANG

    2015-12-01

    Full Text Available Abstract 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.

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

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    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. Contributions of the South Asian Society on Atherosclerosis and Thrombosis and the Indian Society for Atherosclerosis Research, to our understanding of Atherosclerosis and Thrombosis

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    Gundu H R Rao

    2016-01-01

    Full Text Available South Asians (Indians, Bangladeshis, Pakistanis and Sri Lankans have very high incidence of cardiometabolic diseases, such as hypertension, central abdominal obesity, metabolic syndrome, type-2 diabetes, ischemic heart disease and stroke. To create awareness, develop educational and a prevention program, a professional society was started at the University of Minnesota in 1993. This society (South Asian Society on Atherosclerosis Thrombosis organized international conferences in India every other year, on the topic of "Atherosclerosis and Thrombosis" and published several monographs on this subject. During the same period, another sister society, Indian Society of Atherosclerosis Research (ISAR was started in India, which organized conferences on topics related to basic research and clinical aspects of atherosclerosis. Together, these professional societies have contributed significantly to our understanding of chronic cardiometabolic diseases. SASAT is currently located at the Division of Clinical and Preventive Cardiology, Medanta, The MediCity, New Delhi, India and is affiliated with the professional journal; Journal of Clinical and Preventive Cardiology. For information on ISAR, readers are urged to visit their web site: www. isar.co.in.

  14. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

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    Jesus A Araujo

    2012-07-01

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

  15. High prevalence of COPD in atherosclerosis patients

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    Tuleta I

    2017-10-01

    Full Text Available Izabela Tuleta, Tarik Farrag, Laura Busse, Carmen Pizarro, Christian Schaefer, Simon Pingel, Georg Nickenig, Dirk Skowasch, Nadjib Schahab Department of Internal Medicine II – Cardiology, Pulmonology and Angiology, University of Bonn, Bonn, Germany Abstract: Atherosclerosis and COPD are both systemic inflammatory diseases that may influence each other. The aim of the present study was to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease and to assess factors associated with the presence of COPD. Following the diagnosis of cerebral and/or peripheral artery disease by means of duplex sonography, 166 consecutive patients underwent body plethysmography with capillary blood gas analysis. Thereafter, blood tests with determination of different parameters such as lipid profile, inflammatory and coagulation markers were conducted in remaining 136 patients who fulfilled inclusion criteria of the study. Thirty-six out of 136 patients suffered from COPD, mostly in early stages of the disease. Residual volume indicating emphysema was increased (162.9%±55.9% vs 124.5%±37.0%, p<0.05 and diffusion capacity was decreased (55.1%±19.5% vs 75.3%±18.6%, p<0.05 in COPD patients vs non-COPD group. In capillary blood gas analysis, COPD patients had lower partial pressure of oxygen (70.9±11.5 vs 75.2±11.0 mmHg, p<0.05 and higher partial pressure of carbon dioxide (36.8±7.5 vs 34.4±4.4 mmHg, p<0.05 compared with non-COPD individuals. Presence of COPD was associated with predominance of diabetes mellitus, interleukin-8-related systemic neutrophilic inflammation and anemia. In conclusion, COPD is highly prevalent in patients with atherosclerotic artery disease. Keywords: cerebral artery disease, peripheral artery disease, lung function, capillary blood gas, diabetes mellitus, inflammation, interleukin-8, anemia

  16. Cellular Imaging of Inflammation in Atherosclerosis Using Magnetofluorescent Nanomaterials

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    Farouc A. Jaffer

    2006-04-01

    Full Text Available Objective: Magnetofluorescent nanoparticles (MFNPs offer the ability to image cellular inflammation in vivo. To better understand their cellular targeting and imaging capabilities in atherosclerosis, we investigated prototypical dextran-coated near-infrared fluorescent MFNPs in the apolipoprotein E-deficient (apo E−/− mouse model. Methods and Results: In vitro MFNP uptake was highest in activated murine macrophages (p < .001. Apo E−/− mice (n = 11 were next injected with the MFNP (15 mg/kg iron or saline. In vivo magnetic resonance imaging (MRI demonstrated strong plaque enhancement by the MFNPs (p < .001 vs. saline, which was confirmed by multimodality ex vivo MRI and fluorescence reflectance imaging. On fluorescence microscopy, MFNPs were found in cellular-rich areas of atheroma and colocalized with immunofluorescent macrophages over endothelial cells and smooth muscle cells (p < .001. Conclusions: Here we show that (1 the in vitro and in vivo cellular distribution of atherosclerosis-targeted MFNPs can be quantified by using fluorescence imaging methods; (2 in atherosclerosis, dextranated MFNPs preferentially target macrophages; and (3 MFNP deposition in murine atheroma can be noninvasively detected by in vivo MRI. This study thus provides a foundation for using MFNPs to image genetic and/or pharmacological perturbations of cellular inflammation in experimental atherosclerosis and for the future development of novel targeted nanomaterials for atherosclerosis.

  17. Correlation between insulin-induced estrogen receptor methylation and atherosclerosis.

    Science.gov (United States)

    Min, Jia; Weitian, Zhong; Peng, Cai; Yan, Peng; Bo, Zhang; Yan, Wang; Yun, Bai; Xukai, Wang

    2016-11-10

    Hyperinsulinemia and insulin resistance have been recently recognized as an important cause of atherosclerosis. Clinical studies have also found that expression of the estrogen receptor is closely related to the incidence of atherosclerosis. This study investigate the effects of insulin and estrogen receptor α (ER-α) in atherosclerosis. Double knockout ApoE/Lepr mice were given intraperitoneal injections of insulin, and their aortae were harvested for hematoxylin-eosin staining and immunohistochemical analysis. In addition, vascular smooth muscle cells (VSMCs) were treated with insulin or infected with a lentivirus encoding exogenous ER-α, and changes in gene expression were detected by real-time polymerase chain reaction and western blotting. The methylation levels of the ER-α gene were tested using bisulfite sequencing PCR, and flow cytometry and EdU assay were used to measure VSMCs proliferation. Our results showed that insulin can induce the formation of atherosclerosis. Gene expression analysis revealed that insulin promotes the expression of DNA methyltransferases and inhibits ER-α expression, while 5-aza-2'-deoxycytidine can inhibit this effect of insulin. Bisulfite sequencing PCR analysis showed that methylation of the ER-α second exon region increased in VSMCs treated with insulin. The results also showed that ER-α can inhibit VSMCs proliferation. Our data suggest that insulin promotes the expression of DNA methyltransferases, induces methylation of ER-α second exon region and decreases the expression of ER-α, thereby interfering with estrogen regulation of VSMCs proliferation, resulting in atherosclerosis.

  18. Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis

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    Ernesto Oviedo-Orta

    2008-06-01

    Full Text Available Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs, beta2glycoprotein1 (β2GP1, lipoprotein a (LP(a, heat shock proteins (HSPs, and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques.

  19. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    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. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  20. 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.

  1. Cardiovascular Autonomic Neuropathy and Early Atherosclerosis in Adolescent Type 1 Diabetic Patient

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    Soha M. Abd El Dayem

    2015-12-01

    CONCLUSION: Percentage of arrhythmia and early atherosclerosis is high in adolescent type 1 diabetic patients. CAN is associated with early atherosclerosis. Cardiac autonomic neuropathy is associated with older age, longer duration, and poor glycemic control and microalbuminuria.

  2. White blood cell count is associated with carotid and femoral atherosclerosis

    NARCIS (Netherlands)

    Ortega, Emilio; Gilabert, Rosa; Nuñez, Isabel; Cofán, Montserrat; Sala-Vila, Aleix; de Groot, Eric; Ros, Emili

    2012-01-01

    Objective: Chronic low-grade inflammation is associated with atherosclerosis. Ultrasound imaging allows measurement of intima-media thickness (IMT) and plaque. We investigated the association between inflammatory markers and carotid and femoral atherosclerosis. Methods: We studied 554 subjects with

  3. Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases

    NARCIS (Netherlands)

    Bijl, M

    Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune

  4. 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

    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

  5. Association of scavenger receptor class B type I polymorphisms with subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Naj, Adam C; West, Michael; Rich, Stephen S; Post, Wendy; Kao, W H Linda; Wasserman, Bruce A; Herrington, David M; Rodriguez, Annabelle

    2010-02-01

    Little is known about the association of scavenger receptor class B type I (SCARB1) single-nucleotide polymorphisms (SNPs) and subclinical atherosclerosis, particularly in subjects of different racial/ethnic backgrounds. We examined this relationship in the Multi-Ethnic Study of Atherosclerosis. Forty-three SCARB1-tagging SNPs were genotyped. Baseline examinations included fasting lipids and subclinical atherosclerosis phenotypes (coronary artery calcification, common carotid intimal-medial artery thickness [CCIMT], and internal carotid intimal-medial artery thickness). Examining SNP associations with different subclinical atherosclerosis phenotypes across multiple racial/ethnic groups with adjustment for multiple covariates, we found that the C allele of SNP rs10846744 was associated with higher CCIMT in African American (P=0.03), Chinese (P=0.02), European American (P=0.05), and Hispanic participants (P=0.03) and was strongly associated in pooled analyses (P=0.0002). The results also showed that the association of this SNP with CCIMT was independent of lipids and other well-established cardiovascular risk factors. Stratifying by sex, there seemed to be a strong association of rs10846744 with CCIMT in women, but no genotype-sex interactions were observed. Variation in SCARB1 at rs10846744 was significantly associated with CCIMT across racial/ethnic groups in Multi-Ethnic Study of Atherosclerosis.

  6. Progress in HDL-based therapies for atherosclerosis.

    Science.gov (United States)

    Chyu, Kuang-Yuh; Peter, Anish; Shah, Prediman K

    2011-10-01

    Atherosclerosis is a chronic inflammatory disease affecting medium and large arteries resulting from a complex interaction between genetic and environmental risk factors that include dyslipidemia, hypertension, diabetes mellitus, and smoking. The most serious manifestations of atherosclerotic vascular disease, such as unstable angina, myocardial infarction, ischemic stroke, and sudden death, largely result from thrombosis superimposed on a disrupted (ruptured or eroded) atherosclerotic plaque. Adoption and maintenance of a healthy lifestyle coupled with management of modifiable risk factors significantly reduce the adverse clinical consequences of athero-thrombosis. Reducing low-density lipoprotein cholesterol levels using statins and other agents serves as the primary pharmacologic approach to stabilize atherosclerotic vascular disease. However, a large residual risk remains, prompting the search for additional therapies for atherosclerosis management, such as raising atheroprotective high-density lipoprotein (HDL) and/or improving HDL function. This review focuses on new and emerging HDL-based therapeutic strategies targeting atherosclerosis.

  7. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    ) in the endothelia of Apoe(-/-) mice (Irs1/Apoe(-/-)) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE(-/-) mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable......Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1...... induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1...

  8. Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies

    Science.gov (United States)

    Yang, Xinyu; Li, Yang; Li, Yanda; Ren, Xiaomeng; Zhang, Xiaoyu; Hu, Dan; Gao, Yonghong; Xing, Yanwei; Shang, Hongcai

    2017-01-01

    Atherogenesis, the formation of atherosclerotic plaques, is a complex process that involves several mechanisms, including endothelial dysfunction, neovascularization, vascular proliferation, apoptosis, matrix degradation, inflammation, and thrombosis. The pathogenesis and progression of atherosclerosis are explained differently by different scholars. One of the most common theories is the destruction of well-balanced homeostatic mechanisms, which incurs the oxidative stress. And oxidative stress is widely regarded as the redox status realized when an imbalance exists between antioxidant capability and activity species including reactive oxygen (ROS), nitrogen (RNS) and halogen species, non-radical as well as free radical species. This occurrence results in cell injury due to direct oxidation of cellular protein, lipid, and DNA or via cell death signaling pathways responsible for accelerating atherogenesis. This paper discusses inflammation, mitochondria, autophagy, apoptosis, and epigenetics as they induce oxidative stress in atherosclerosis, as well as various treatments for antioxidative stress that may prevent atherosclerosis. PMID:28878685

  9. 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.

  10. 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.

  11. Generalized atherosclerosis, cognitive decline, and depressive symptoms in old age.

    Science.gov (United States)

    Vinkers, D J; Stek, M L; van der Mast, R C; de Craen, A J M; Le Cessie, S; Jolles, J; Westendorp, R G J; Gussekloo, J

    2005-07-12

    Atherosclerosis may be linked to cognitive decline and depression in old age. The Leiden 85-Plus Study is a prospective population-based study of 599 subjects from age 85 onward. The generalized atherosclerotic burden was rated by the number of cardiovascular pathologies at baseline, as assessed by history taking from treating physicians and EKG. Cardiovascular pathologies included myocardial infarction, angina pectoris or myocardial ischemia, claudicatio intermittens, and arterial surgery. Global cognitive function (Mini-Mental State Examination), attention (Stroop Test), processing speed (Letter Digit Coding Test), immediate recall memory (Word Learning Test-Immediate Recall), delayed recall memory (Word Learning Test-Delayed Recall), and depressive symptoms (15-item Geriatric Depression Scale) were assessed each year from ages 85 through 90. The prospective associations between both the generalized atherosclerosis rating and stroke with cognitive function and depressive symptoms were analyzed by linear mixed models adjusted for sex and level of education. During follow-up, there was a significant cognitive decline and a significant increase of depressive symptoms. At baseline, a history of stroke was correlated with lower global cognitive function, slower processing speed, impaired immediate and delayed recall memory, and more depressive symptoms. In addition, a higher generalized atherosclerosis rating was correlated with impaired global cognitive function, lower attention, and a slower processing speed at baseline. During follow-up, a higher generalized atherosclerosis rating was associated with an accelerated decline of immediate recall memory and delayed recall memory. In contrast, there was no relation between the generalized atherosclerosis rating and depressive symptoms, either in the cross-sectional analysis or in the prospective analysis. In the population at large, generalized atherosclerosis contributes to cognitive decline in old age but not to

  12. Metabolically healthy obesity and the risk for subclinical atherosclerosis.

    Science.gov (United States)

    Kim, Tae Jun; Shin, Hee-Young; Chang, Yoosoo; Kang, Mira; Jee, Jaehwan; Choi, Yoon-Ho; Ahn, Hyeon Seon; Ahn, Soo Hyun; Son, Hee Jung; Ryu, Seungho

    2017-07-01

    Although obesity and metabolic abnormalities are known risk factors for cardiovascular disease, the risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as metabolically healthy obese (MHO), remains unclear. We examined the association between body mass index categories and the development of subclinical carotid atherosclerosis in a cohort of metabolically healthy individuals. We conducted a cohort study of 6453 men without subclinical carotid atherosclerosis or metabolic abnormalities at baseline, who underwent repeated health check-up examinations that included carotid ultrasound. A metabolically healthy state was defined as having no metabolic syndrome components and a homeostasis model assessment of insulin resistance Subclinical carotid atherosclerosis was assessed using ultrasound. During the follow-up period of 34,797.9 person-years, subclinical carotid atherosclerosis developed in 1916 participants. Comparing overweight and obese with normal weight participants, the multivariable adjusted hazard ratios (95% confidence intervals) for incident subclinical carotid atherosclerosis were 1.24 (1.12-1.38) and 1.54 (1.38-1.72), respectively. The association persisted after further adjustment for metabolic variables. This association was also evident in MHO men without abdominal obesity (waist circumference > 90 cm) and it did not differ across any clinically relevant subgroups evaluated. In a large cohort study of strictly defined metabolically healthy participants, the MHO phenotype was associated with an increased risk of incident subclinical carotid atherosclerosis, providing evidence that the MHO phenotype is not protective from cardiovascular risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

    Science.gov (United States)

    Vargas, Jose D; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Rotter, Jerome I; Post, Wendy S; Polak, Joseph F; Budoff, Matthew J; Bluemke, David A

    2016-02-01

    Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds. The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66). In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN. Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations. Published by Elsevier Ireland Ltd.

  14. Targeting and therapeutic peptides in nanomedicine for atherosclerosis.

    Science.gov (United States)

    Chung, Eun Ji

    2016-05-01

    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 is provided, including peptides designed for cellular targets such as endothelial cells, monocytes, and macrophages as well as for plaque components such as collagen and fibrin. An emphasis is placed on recent advances in multimodal strategies and a discussion on current challenges and barriers for clinical applicability is presented. © 2016 by the Society for Experimental Biology and Medicine.

  15. [¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

    2015-01-01

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

  16. Accumulation of advanced glycation end products in canine atherosclerosis.

    Science.gov (United States)

    Chiers, K; Vandenberge, V; Ducatelle, R

    2010-07-01

    Atherosclerosis is an uncommon lesion in animals and particularly in dogs. Prominent atherosclerotic lesions of the coronary arteries are described in three dogs. These comprised an expansion of the tunica media by the accumulation of foam cells and/or cholesterol crystals, with subsequent narrowing of the vascular lumen. Immunohistochemical analysis revealed the accumulation of advanced glycation end products (AGEs) in foam cells, macrophages and lymphocytes. As in man, these findings suggest a possible role of AGEs in the development of canine atherosclerosis. (c) 2009 Elsevier Ltd. All rights reserved.

  17. The Influence of Innate and Adaptive Immune Responses on Atherosclerosis

    Science.gov (United States)

    Witztum, Joseph L.; Lichtman, Andrew H.

    2014-01-01

    Both the chronic development of atherosclerotic lesions and the acute changes in lesion phenotype that lead to clinical cardiovascular events are significantly influenced by the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall. The rapid pace of discovery of mechanisms of immunologic recognition, effector functions, and regulation has significantly influenced the study of atherosclerosis, and our new knowledge is beginning to affect how we treat this ubiquitous disease. In this review, we discuss recent advances in our understanding of how innate and adaptive immunity contribute to atherosclerosis, as well as therapeutic opportunities that arise from this knowledge. PMID:23937439

  18. Lutein and atherosclerosis: Belfast versus Toulouse revisited.

    Science.gov (United States)

    Howard, A N; Thurnham, D I

    2017-01-01

    have been due to the effects of concurrent high concentrations of plasma lutein on the immune system and complement in particular. Other carotenoids may exert similar antioxidant effects but we and others found no differences in antioxidant nutrients between subjects in Toulouse and Belfast or between subjects with asymptomatic markers of atherosclerosis and controls. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis

    Directory of Open Access Journals (Sweden)

    Aoki Toshinari

    2012-01-01

    Full Text Available Abstract Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR, 1.034; 95% confidence interval (95%CI, 1.010 - 1.059, HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225, and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051 were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

  20. Association of mitochondrial genetic variation with carotid atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Igor A Sobenin

    Full Text Available In human pathology, several diseases are associated with somatic mutations in the mitochondrial genome (mtDNA. Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. In this study we analyzed the association of mitochondrial genetic variation with the severity of carotid atherosclerosis, as assessed by carotid intima-media thickness (cIMT and the presence of coronary heart disease (CHD in 190 subjects from Moscow, Russia, a population with high CHD occurrence. cIMT was measured by high-resolution B-mode ultrasonography and mtDNA heteroplasmies by a pyrosequencing-based method. We found that heteroplasmies for several mutations in the mtDNA in leukocytes, including C3256T, T3336C, G12315A, G13513A, G14459A, G14846A, and G15059A mutations, were significantly (p<0.001 associated with both the severity of carotid atherosclerosis and the presence of CHD. These findings indicate that somatic mitochondrial mutations have a role in the development of atherosclerosis.

  1. Identification and characterization of biomarkers in atherosclerosis and diabetes

    OpenAIRE

    Nieddu, Gabriele

    2015-01-01

    Diabetes and atherosclerosis are two chronic pathologies which prevalence is constantly growing worldwide, leading to disability and life-threatening complications. Since their consequences represent major causes of mortality and morbidity in developed countries, the identification and characterisation of new potential biomarkers may contribute to revealing the underlying mechanisms of pathology onset and progression, and to improving the diagnostic methodologies and the therapeutic approache...

  2. Reverse cholesterol transport : a potential therapeutic target for atherosclerosis

    NARCIS (Netherlands)

    Zhao, Ying

    2011-01-01

    Atherosclerosis is the major cause of death in the Western society due to the development of acute clinical events such as myocardial infarction and cerebral stroke. Currently, lowering plasma LDL cholesterol (LDL-C) levels using statins, inhibitors of de-novo cholesterol synthesis, is the main

  3. histomorphological features of atherosclerosis in the left anterior ...

    African Journals Online (AJOL)

    2017-11-12

    Nov 12, 2017 ... The pattern of coronary artery atherosclerosis is valuable in informing mitigation strategies for coronary heart disease. Histomorphological data on this disease among Africans living in Sub Saharan Africa are, however, scarce. The left anterior descending is one of the most commonly afflicted arteries. This.

  4. Generalized atherosclerosis, cognitive decline, and depressive symptoms in old age

    NARCIS (Netherlands)

    Vinkers, D.J.; Stek, M.L.; van der Mast, R.C.; de Craen, A.J.; Le Cessie, S.; Jolles, J.; Westendorp, R.G.; Gussekloo, J.

    2005-01-01

    BACKGROUND: Atherosclerosis may be linked to cognitive decline and depression in old age. METHODS: The Leiden 85-Plus Study is a prospective population-based study of 599 subjects from age 85 onward. The generalized atherosclerotic burden was rated by the number of cardiovascular pathologies at

  5. Plasma IL-5 concentration and subclinical carotid atherosclerosis

    NARCIS (Netherlands)

    Silveira, Angela; McLeod, Olga; Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Deleskog, Anna; Persson, Jonas; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Gustafsson, Sven; Soderberg, Stefan; Ohrvik, John; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Hamsten, Anders

    Objective: Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early

  6. Human Low Density Lipoprotein as a Vehicle of Atherosclerosis ...

    African Journals Online (AJOL)

    Low-density lipoproteins have been sufficiently established as an important precursor of atherosclerosis. The actual mechanism is still unclear, and the current technique of using radioisotopes has clinical limitation. However, the current study techniques or methods excellently elucidate the functional aspects of ...

  7. Is there an association between coronary atherosclerosis and ...

    African Journals Online (AJOL)

    2012-09-25

    Sep 25, 2012 ... Background:Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades.

  8. Atherosclerosis and Nutrition with Special Reference to Populations ...

    African Journals Online (AJOL)

    Severe atherosclerosis and its sequelae-coronary heart disease, cerebral vascular disease, and peripheral vascular disease-share major responsibility for half the mortality rate in affluent Western populations. In Africa, particularly South Africa, a study of the extent and severity of lesions is particularly interesting because of ...

  9. Atherosclerosis – A Review | Amballi | Nigerian Medical Practitioner

    African Journals Online (AJOL)

    ... are present in smaller amounts. Past studies have also indicated that essential fatty acid (EFA) and Vitamin E prevent atherogenesis. This review emphasizes the biochemical events of atherogenesis as well as the role of Chlamydia pneumoniae in atherosclerosis. Nigerian Medical Practitioner Vol. 48 (1), 2005: 22 - 28 ...

  10. Fibrinogen and atherosclerosis: A study in transgenic mice

    NARCIS (Netherlands)

    Koopman, J.; Havekes, L.; Verheijen, J.; Gijbels, M.; Haverkate, F.

    1996-01-01

    Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular

  11. Fibrinogen and atherosclerosis: A study in transgenic mice

    NARCIS (Netherlands)

    Koopman, J.; Maas, A.; Rezaee, F.; Havekes, L.; Verheijen, J.; Gijbels, M.; Haverkate, F.

    1997-01-01

    Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular

  12. Imaging Techniques for Diagnosis of Thoracic Aortic Atherosclerosis

    NARCIS (Netherlands)

    Jansen Klomp, W.W.; Jansen Klomp, W.W.; Brandon Bravo Bruinsma, G.J.; van 't Hof, A.W.; Grandjean, Jan G; Nierich, A.P.

    2016-01-01

    The most severe complications after cardiac surgery are neurological complications including stroke which is often caused by emboli merging from atherosclerosis in the ascending aorta to the brain. Information about the thoracic aorta is crucial in reducing the embolization risk for both surgical

  13. A Role of the Bile Salt Receptor FXR in Atherosclerosis

    NARCIS (Netherlands)

    Hageman, Jurre; Herrema, Hilde; Groen, Albert K.; Kuipers, Folkert

    This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly

  14. A Role of the Bile Salt Receptor FXR in Atherosclerosis

    NARCIS (Netherlands)

    Hageman, J.; Herrema, H.J.; Groen, A.K.; Kuipers, F.

    2010-01-01

    This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly

  15. Insulin resistance and atherosclerosis : the role of visceral fat

    NARCIS (Netherlands)

    Gast, K.B.

    2016-01-01

    The main objective of this thesis was to unravel relationships between obesity, insulin resistance, hyperglycemia, and atherosclerosis. It is well-established that patients with type 2 diabetes have a 2- to 3-fold increased risk of cardiovascular disease. We investigated whether insulin resistance

  16. Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis

    NARCIS (Netherlands)

    A.F.L. Schinkel (Arend); M. Kaspar (Mathias); D. Staub (Daniel)

    2016-01-01

    textabstractContrast-enhanced ultrasound (CEUS) is increasingly being used to evaluate patients with known or suspected atherosclerosis. The administration of a microbubble contrast agent in conjunction with ultrasound results in an improved image quality and provides information that cannot be

  17. A Modified Sesamol Derivative Inhibits Progression of Atherosclerosis

    Science.gov (United States)

    Ying, Zhekang; Kherada, Nisharahmed; Kampfrath, Thomas; Mihai, Georgeta; Simonetti, Orlando; Desikan, Rajagopal; Selvendiran, Karuppaiyah; Sun, Qinghua; Ziouzenkova, Ouiliana; Parthasarathy, Sampath; Rajagopalan, Sanjay

    2017-01-01

    Objective Sesamol, a phenolic component of lignans, has been previously shown to reduce lipopolysaccharide-induced oxidative stress and upregulate phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase pathways. In the present study, we synthesized a modified form of sesamol (INV-403) to enhance its properties and assessed its effects on atherosclerosis. Methods and Results Watanabe heritable hyperlipidemic rabbits were fed with high-cholesterol chow for 6 weeks and then randomized to receive high-cholesterol diet either alone or combined with INV-403 (20 mg/kg per day) for 12 weeks. Serial MRI analysis demonstrated that INV-403 rapidly reduced atherosclerotic plaques (within 6 weeks), with confirmatory morphological analysis at 12 weeks posttreatment revealing reduced atherosclerosis paralleled by reduction in lipid and inflammatory cell content. Consistent with its effect on atherosclerosis, INV-403 improved vascular function (decreased constriction to angiotensin II and increased relaxation to acetylcholine), reduced systemic and plaque oxidative stress, and inhibited nuclear factor–κB activation via effects on nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation with coordinate reduction in key endothelial adhesion molecules. In vitro experiments in cultured endothelial cells revealed effects of INV-403 in reducing IκBα phosphorylation via inhibition of IκB kinase 2 (IKK2). Conclusion INV-403 is a novel modified lignan derivative that potently inhibits atherosclerosis progression via its effects on IKK2 and nuclear factor–κB signaling. PMID:21183734

  18. Intra‑operative grading of coronary artery atherosclerosis associated ...

    African Journals Online (AJOL)

    Background: Atherosclerosis is one of the common causes of morbidity and mortality, in postmenopausal women. Homocysteine, a sulfur‑containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular diseases. This study was designed to evaluate the relationship ...

  19. Histomorphological features of atherosclerosis in the left anterior ...

    African Journals Online (AJOL)

    The pattern of coronary artery atherosclerosis is valuable in informing mitigation strategies for coronary heart disease. Histomorphological data on this disease among Africans living in Sub Saharan Africa are, however, scarce. The left anterior descending is one of the most commonly afflicted arteries. This study, therefore ...

  20. Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes.

    NARCIS (Netherlands)

    Aengevaeren, V.L.; Mosterd, A.; Braber, T.L.; Prakken, N.H.J.; Doevendans, P.A.; Grobbee, D.E.; Thompson, P.D.; Eijsvogels, T.M.H.; Velthuis, B.K.

    2017-01-01

    Background -Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and CVD outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine

  1. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Xin-Fang Leong

    2015-01-01

    Full Text Available 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. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies.

  2. A study of iron status in patients with coronary atherosclerosis

    Directory of Open Access Journals (Sweden)

    faride Doostan

    2004-06-01

    Conclusions: Because the mean of TIBC for male patients with CAD was significantly lower than the mean of ITBC for males without CAD, it was concluded that the iron status of arteries may have a role in atherosclerosis in males patients.

  3. Fibrinolytic activity in peripheral atherosclerosis in the elderly.

    Science.gov (United States)

    van der Bom, J G; Bots, M L; Haverkate, F; Meyer, P; Hofman, A; Grobbee, D E; Kluft, C

    1999-02-01

    Increased concentrations of plasminogen activator inhibitor type 1 (PAI-1) and of D-dimer have jointly been found in subjects with cardiovascular disease. To understand this apparent paradox of increased inhibition of fibrinolysis (high PAI-1) combined with increased fibrinolytic activity (high D-dimer), we examined the relation between D-dimer, PAI-1 and the activator of fibrinolysis, tissue type plasminogen activator (t-PA) in subjects with varying severity of peripheral atherosclerosis. In 325 subjects selected from the Rotterdam Study, a cohort of 7983 men and women aged 55 years and over, the ankle to brachial systolic blood pressure ratio, t-PA antigen and activity, PAI-1 antigen and D-dimer were measured. T-PA antigen and t-PA activity were, independent from each other, increased with degree of atherosclerosis; t-PA antigen increased with 3.5 ng/ml (SE 1.7, p = 0.04) and t-PA activity with 0.46 IU/ml (0.20, p = 0.02) per unit decrease in ankle to brachial pressure ratio (i.e. increase in atherosclerosis). PAI-1 antigen was not related to atherosclerosis. More marked atherosclerosis was associated with increased D-dimer, mainly in subgroups with PAI-1 antigen below 50 ng/ml, t-PA antigen below 10 ng/ml, or t-PA activity above 1.5 IU/ml. In contrast to current beliefs, we found that only a fraction of the variation of t-PA antigen was due to the variation in circulating PAI-1 antigen. A slight positive association was observed between t-PA antigen and D-dimer. PAI-1 and t-PA activity were not associated with D-dimer concentration. In conclusion, in subjects with peripheral atherosclerosis PAI-1 antigen is not increased, but low PAI-1 levels (and possibly also low levels of t-PA antigen and high levels of t-PA activity) appear to be required to increase circulating D-dimer. This suggests that increased D-dimer levels in subjects with atherosclerosis do not reflect increased inhibition, but rather reflect increased fibrinolysis.

  4. Subclinical atherosclerosis and obesity phenotypes among Mexican Americans.

    Science.gov (United States)

    Laing, Susan T; Smulevitz, Beverly; Vatcheva, Kristina P; Rahbar, Mohammad H; Reininger, Belinda; McPherson, David D; McCormick, Joseph B; Fisher-Hoch, Susan P

    2015-03-18

    Data on the influence of obesity on atherosclerosis in Hispanics are inconsistent, possibly related to varying cardiometabolic risk among obese individuals. We aimed to determine the association of obesity and cardiometabolic risk with subclinical atherosclerosis in Mexican-Americans. Participants (n=503) were drawn from the Cameron County Hispanic Cohort. Metabolic health was defined as 5.13; or high-sensitivity C-reactive protein >3 mg/L. Carotid intima media thickness (cIMT) was measured. A high proportion of participants (77.8%) were metabolically unhealthy; they were more likely to be male, older, with fewer years of education, and less likely to meet daily recommendations regarding fruit and vegetable servings. One-third (31.8%) had abnormal carotid ultrasound findings. After adjusting for covariates, mean cIMT varied across the obesity phenotypes (P=0.0001); there was no difference among the metabolically unhealthy regardless of whether they were obese or not. In multivariable analysis, after adjusting for covariates, cardiometabolic risk (P=0.0159), but not obesity (P=0.1446), was significantly associated with subclinical atherosclerosis. In Mexican-Americans, cardiometabolic risk has a greater effect on early atherosclerosis development than body mass index. Non-obese but metabolically unhealthy participants had similar development of subclinical atherosclerosis as their obese counterparts. Interventions to maintain metabolic health among obese and non-obese patients may be a more important goal than weight loss alone. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  5. 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

  6. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis.

    Science.gov (United States)

    Hoseini, Zahra; Sepahvand, Fatemeh; Rashidi, Bahman; Sahebkar, Amirhossein; Masoudifar, Aria; Mirzaei, Hamed

    2018-03-01

    Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1β and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1β, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK-1 and ASK-1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK-induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained. © 2017 Wiley Periodicals, Inc.

  7. Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis

    Science.gov (United States)

    Linton, MacRae F.; Babaev, Vladimir R.; Huang, Jiansheng; Linton, Edward F.; Tao, Huan; Yancey, Patricia G.

    2017-01-01

    Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes. Akt displays isoform-specific effects on atherogenesis, which vary with different vascular cell types. Loss of macrophage Akt2 promotes the anti-inflammatory M2 phenotype and reduces atherosclerosis. However, Akt isoforms are redundant with regard to apoptosis. c-Jun NH2-terminal kinase (JNK) is a pro-apoptotic effector of the UPR, and the JNK1 isoform opposes anti-apoptotic Akt signaling. Loss of JNK1 in hematopoietic cells protects macrophages from apoptosis and accelerates early atherosclerosis. IκB kinase α (IKKα, a member of the serine/threonine protein kinase family) plays an important role in mTORC2-mediated Akt signaling in macrophages, and IKKα deficiency reduces macrophage survival and suppresses early atherosclerosis. Efferocytosis involves the interaction of receptors, bridging molecules, and apoptotic cell ligands. Scavenger receptor class B type I is a critical mediator of macrophage efferocytosis via the Src/PI3K/Rac1 pathway in atherosclerosis. Agonists that resolve inflammation offer promising therapeutic potential to promote efferocytosis and prevent atherosclerotic clinical events. PMID:27725526

  8. Advanced atherosclerosis is associated with increased medial degeneration in sporadic ascending aortic aneurysms.

    Science.gov (United States)

    Albini, Paul T; Segura, Ana Maria; Liu, Guanghui; Minard, Charles G; Coselli, Joseph S; Milewicz, Dianna M; Shen, Ying H; LeMaire, Scott A

    2014-02-01

    The pathogenesis of non-familial, sporadic ascending aortic aneurysms (SAAA) is poorly understood, and the relationship between ascending aortic atherosclerosis and medial degeneration is unclear. We evaluated the prevalence and severity of aortic atherosclerosis and its association with medial degeneration in SAAA. Atherosclerosis was characterized in ascending aortic tissues collected from 68 SAAA patients (mean age, 62.9 ± 12.0 years) and 15 controls (mean age, 56.6 ± 11.4 years [P = 0.07]) by using a modified American Heart Association classification system. Upon histologic examination, 97% of SAAA patients and 73% of controls showed atherosclerotic changes. Most SAAA samples had intermediate (types 2 and 3, 35%) or advanced atherosclerosis (types ≥ 4; 40%), whereas most control samples showed minimal atherosclerosis (none or type 1, 80%; P atherosclerosis grade. Advanced atherosclerosis was associated with higher grades of smooth muscle cell depletion (P atherosclerosis than in patients with minimal (P = 0.04) or intermediate atherosclerosis (P = 0.04). Immunostaining showed marked CD3+ T-cell and CD68+ macrophage infiltration, MMP-2 and MMP-9 production, and cryopyrin expression in the medial layer adjacent to atherosclerotic plaque. SAAA tissues exhibited advanced atherosclerosis that was associated with severe medial degeneration and increased aortic diameter. Our findings suggest a role for atherosclerosis in the progression of sporadic ascending aortic aneurysms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence.

    Science.gov (United States)

    Wang, Julie C; Bennett, Martin

    2012-07-06

    Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.

  10. Imaging subclinical atherosclerosis: is it ready for prime time? A review.

    Science.gov (United States)

    Fernández-Friera, Leticia; Ibáñez, Borja; Fuster, Valentín

    2014-10-01

    Imaging subclinical atherosclerosis holds the promise of individualized cardiovascular (CV) risk assessment. The large arsenal of noninvasive imaging techniques available today is playing an increasingly important role in the diagnosis and monitoring of subclinical atherosclerosis. However, there is a debate about the advisability of clinical screens for subclinical atherosclerosis and which modality is the most appropriate for monitoring risk and atherosclerosis progression. This article offers an overview of the traditional and emerging noninvasive imaging modalities used to detect early atherosclerosis, surveys population studies addressing the value of subclinical atherosclerosis detection, and also examines guideline recommendations for their clinical implementation. The clinical relevance of this manuscript lies in the potential of current imaging technology to improve CV risk prediction based on traditional risk factors and the present recommendations for subclinical atherosclerosis assessment. Noninvasive imaging will also help to identify individuals at high CV who would benefit from intensive prevention or therapeutic interventions.

  11. Global DNA methylation and risk of subclinical atherosclerosis in young adults: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study

    Science.gov (United States)

    Bressler, Jan; Shimmin, Lawrence C.; Boerwinkle, Eric; Hixson, James E.

    2011-01-01

    Objective The association between hepatic global DNA methylation measured using pyrosequencing technology and the risk of subclinical atherosclerosis was examined in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. PDAY is a bi-racial investigation of the natural history of atherosclerosis and its risk factors involving 3013 individuals aged 15–34 years who underwent autopsy after dying of unrelated causes in 1987–1994. Methods Raised atherosclerotic lesions were defined as the sum of the percentages of intimal surface area detected in the right coronary artery and left half of the abdominal and thoracic aorta harboring fibrous plaques, complicated lesions, and calcified lesions during a postmortem pathological examination. To conduct the case–control study, 300 cases selected with the highest raised lesion scores were paired with 300 controls without raised lesions after matching for age, race, and gender. Results Global DNA methylation was not associated with disease risk in the study population considered as a whole using conditional logistic regression models to analyze matched pairs. Since the estimation of the risk of atherosclerosis associated with inter-individual variation in DNA methylation was similar if unconditional logistic regression was used, subgroup analyses were carried out after adjusting for matching variables. A modest association with methylation levels below the median value was found in white but not in African-American study participants (odds ratio = 1.59, 95% confidence interval = 1.02–2.49, p = 0.04). Conclusions Hepatic global DNA methylation does not appear to be a definitive determinant of atherosclerosis burden in a postmortem sample of young adults. PMID:22015179

  12. Subclinical atherosclerosis in low Framingham risk HIV patients.

    Science.gov (United States)

    León, Rafael; Reus, Sergio; López, Nicolás; Portilla, Irene; Sánchez-Payá, José; Giner, Livia; Boix, Vicente; Merino, Esperanza; Torrús, Diego; Moreno-Pérez, Óscar; Portilla, Joaquín

    2017-08-01

    Pathogenesis of atherosclerosis is complex, and differences between HIV-infected patients and general population cannot be completely explained by the higher prevalence of traditional cardiovascular risk factors. We aimed to analyse the association between inflammation and subclinical atherosclerosis in HIV patients with low Framingham risk score. Case-control study. Outpatient Infectious Diseases clinic in a university hospital. HIV-1-infected patients aged > 35 years receiving antiretroviral treatment with viral load  5 cigarettes/day; diabetes; hypertension; vascular diseases. subclinical atherosclerosis determined by ultrasonography: common carotid intima-media thickness greater than 0·8 mm or carotid plaque presence. Explanatory variables: ribosomal bacterial DNA (rDNA), sCD14, interleukin-6 (IL-6) and TNF-α. Eighty-four patients were included, 75% male, mean age 42 years and mean CD4+ cells 657 ± 215/mm(3) . Median Framingham risk score was 1% at 10 years (percentile 25-75: 0·5-4%). Eighteen patients (21%) had subclinical atherosclerosis; the associated factors were older age (P = 0·001), waist-hip ratio (P = 0·01), time from HIV diagnosis (P = 0·02), rDNA (P = 0·04) and IL-6 (P = 0·01). In multivariate analysis, OR for subclinical atherosclerosis was 7 (95% CI, 1.3-40, P = 0.02) and 9 (95% CI, 1.0-85, P = 0.04) for patients older than 44 years and IL-6 > 6·6 pg/mL, respectively. Well-controlled HIV patients with low Framingham risk score have a high prevalence of subclinical carotid atherosclerosis, and the main risk factors are age and inflammation. These patients are not receiving primary prophylaxis for cardiovascular events according to current guidelines. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort.

    Science.gov (United States)

    Dolan, Hillary; Crain, Barbara; Troncoso, Juan; Resnick, Susan M; Zonderman, Alan B; Obrien, Richard J

    2010-08-01

    Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts. We examined the relationship between systemic atherosclerosis, Alzheimer type pathology, and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging, a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies. Using a quantitative analysis of atherosclerosis in the aorta, heart, and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible. Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer pathology and stroke through which vascular changes may influence dementia risk.

  14. Atherosclerosis, Dementia, and Alzheimer’s Disease in the BLSA Cohort

    Science.gov (United States)

    Dolan, Hillary; Crain, Barbara; Troncoso, Juan; Resnick, Susan M; Zonderman, Alan B; OBrien, Richard J

    2011-01-01

    Objective Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts. Methods We examined the relationship between systemic atherosclerosis, Alzheimer type pathology and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging (BLSA), a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies. Results Using a quantitative analysis of atherosclerosis in the aorta, heart and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer’s type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible. Interpretation Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer’s pathology and stroke through which vascular changes may influence dementia risk. PMID:20695015

  15. Genetics of HDL-C: a causal link to atherosclerosis?

    Science.gov (United States)

    van Capelleveen, Julian C; Bochem, Andrea E; Motazacker, M Mahdi; Hovingh, G Kees; Kastelein, John J P

    2013-06-01

    Prospective epidemiological studies have consistently reported an inverse association between HDL cholesterol (HDL-C) levels and the risk of cardiovascular disease (CVD). However, large intervention trials on HDL-C-increasing drugs and recent Mendelian randomization studies have questioned a causal relationship between HDL-C and atherosclerosis. HDL-C levels have been shown to be highly heritable, and the combination of HDL-C-associated SNPs in recent large-scale genome-wide association studies (GWAS) only explains a small proportion of this heritability. As a large part of our current understanding of HDL metabolism comes from genetic studies, further insights in this research field may aid us in elucidating HDL functionality in relation to CVD risk. In this review we focus on the question of whether genetically defined HDL-C levels are associated with risk of atherosclerosis. We also discuss the latest insights for HDL-C-associated genes and recent GWAS data.

  16. HDL and immunomodulation: an emerging role of HDL against atherosclerosis.

    Science.gov (United States)

    Yu, Bi-lian; Wang, Shu-hui; Peng, Dao-quan; Zhao, Shui-ping

    2010-01-01

    Changes in plasma lipoprotein profiles, particularly low levels of high-density lipoprotein (HDL) cholesterol, are associated with several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis, implying the potential link between HDL and immunity. Accumulating evidence suggests that HDL possesses anti-inflammatory effects and has an important function in host defense as part of the innate immune system. In addition, HDL inhibits the ability of antigen-presenting cells (APCs) to stimulate T cells. It is subsequently discovered that HDL or HDL-associated platelet-activating factor-acetylhydrolase can restore the emigratory process of monocyte-derived dendritic cells and thus result in resolution of inflammatory reactions in atherosclerotic plaques. Lipid rafts in plasma membrane are the key structure responsible for the immunomodulation effects of HDL, the remarkable ability of HDL to regulate innate and adaptive immune responses extends our understanding of its atheroprotective role, and provides new therapeutic approaches to atherosclerosis and other inflammatory conditions.

  17. Hybrid FMT-MRI applied to in vivo atherosclerosis imaging.

    Science.gov (United States)

    Li, Baoqiang; Maafi, Foued; Berti, Romain; Pouliot, Philippe; Rhéaume, Eric; Tardif, Jean-Claude; Lesage, Frederic

    2014-05-01

    Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice.

  18. Inflammation, thrombosis and atherosclerosis: results of the Glostrup study

    DEFF Research Database (Denmark)

    Maat, M de; Bladbjerg, E-M; Drivsholm, T

    2003-01-01

    of inflammatory and hemostatic markers and the severity of atherosclerosis is not yet well studied. We have evaluated 325 men and 370 women of 60 years, participating in the Danish Glostrup study. We diagnosed atherosclerosis by ultrasonographic measurement of intima-media thickness (IMT) of the right carotid......) antigen, FVII coagulant activity (FVII:C) and activated FVII (FVIIa). DNA variations were determined for fibrinogen, PAI-1, t-PA, FVII, factor XIII and methylene tetrahydrofolate reductase (MTHFR). Subjects with high IMT (upper 10% of distribution, n = 63) had higher CRP levels [2.2 mg L-1 (SE 0.3)] than...... subjects with IMT in the lowest tertile (n = 217) [1.7 mg L-1 (SE 0.1), P = 0.04], whereas there was no association between the hemostatic variables and IMT. There was an association between fibrinogen and d-dimer concentrations and number of plaques (P

  19. Macrophages and Their Contribution to the Development of Atherosclerosis.

    Science.gov (United States)

    Bobryshev, Yuri V; Nikiforov, Nikita G; Elizova, Natalia V; Orekhov, Alexander N

    2017-01-01

    Atherosclerosis can be regarded as chronic inflammatory disease driven by lipid accumulation in the arterial wall. Macrophages play a key role in the development of local inflammatory response and atherosclerotic lesion growth. Atherosclerotic plaque is a complex microenvironment, in which different subsets of macrophages coexist executing distinct, although in some cases overlapping functions. According to the classical simplified nomenclature, lesion macrophages can belong to pro-inflammatory or anti-inflammatory or alternatively activated types. While the former promote the inflammatory response and participate in lipid accumulation, the latter are responsible for the inflammation resolution and plaque stabilisation. Atherosclerotic lesion dynamics depends therefore on the balance between these macrophages populations. The diverse functions of macrophages make them an attractive therapeutic target for the development of novel anti-atherosclerotic treatments. In this chapter, we discuss different types of macrophages and their roles in atherosclerotic lesion dynamics and describe the results of several experiments studying macrophage polarisation in atherosclerosis.

  20. [Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

    Science.gov (United States)

    Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

    2009-01-01

    Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

  1. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Kyung Mook Choi

    2016-03-01

    Full Text Available Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis.

  2. 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

    2016-08-04

    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.

  3. Cytokines: Roles in atherosclerosis disease progression and potential therapeutic targets

    Science.gov (United States)

    Moss, Joe W. E.; Ramji, Dipak P.

    2017-01-01

    Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory disorder in the walls of medium and large arteries. CVD is currently responsible for about one in three global deaths and this is expected to rise in the future due to an increase in the prevalence of obesity and diabetes. Current therapies for atherosclerosis mainly modulate lipid homeostasis and whilst successful at reducing the risk of a CVD-related death, they are associated with considerable residual risk and various side effects. There is therefore a need for alternative therapies aimed at regulating inflammation in order to reduce atherogenesis. This review will highlight the key role cytokines play during disease progression as well as potential therapeutic strategies to target them. PMID:27357616

  4. Extracellular vesicles as new pharmacological targets to treat atherosclerosis.

    Science.gov (United States)

    Yin, Min; Loyer, Xavier; Boulanger, Chantal M

    2015-09-15

    Extracellular vesicles released by most cell types, include apoptotic bodies (ABs), microvesicles (MVs) and exosomes. They play a crucial role in physiology and pathology, contributing to "cell-to-cell" communication by modifying the phenotype and the function of target cells. Thus, extracellular vesicles participate in the key processes of atherosclerosis from endothelial dysfunction, vascular wall inflammation to vascular remodeling. The purpose of this review is to summarize recent findings on extracellular vesicle formation, structure, release and clearance. We focus on the deleterious and beneficial effects of extracellular vesicles in the development of atherosclerosis. The potential role of extracellular vesicles as biomarkers and pharmacological targets, their innate therapeutic capacity, or their use for novel drug delivery devices in atherosclerotic cardiovascular diseases will also be discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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.

  7. Platelets and their chemokines in atherosclerosis – clinical applications

    Directory of Open Access Journals (Sweden)

    Philipp evon Hundelshausen

    2014-08-01

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

  8. [Several diagnostic errors in cerebral atherosclerosis (clinico-anatomic study)].

    Science.gov (United States)

    Sotskov, G V

    1979-01-01

    A clinicoanatomical study was conducted in 218 cases of atherosclerotic dementia. 12 cases (5,5% of the total amount) showed diagnostic errors. Atherosclerotic dementia with Alzhemier-like symptomatology during life was considered to be Alzheimers disease, while Alzheimers disease, complicated by cerebral atherosclerosis as atherosclerotic dementia. Some objective and subjective factors of diagnostic errors were established. Late detection of such patients is considered as one of the risk factors of diagnostic errors during life.

  9. Handling and diet-induced atherosclerosis in rabbits.

    Science.gov (United States)

    Jezierski, T; Mekking, P; Wiepkema, P R

    1993-07-01

    Atherosclerosis was induced in rabbits by feeding them a 2% cholesterol diet (CHOL) during a 5-week period. Twelve rabbits were fed with increasing amounts of CHOL food until the ad libitum level was reached, whereas in 24 other rabbits the food was limited to the amount eaten by the lowest consumer of the group to reduce individual variability in total amount of food consumed. Twice a day, half of the rabbits were handled carefully, the other half had normal laboratory practice contact with their caretaker. Feed intake and amount of atherosclerosis were determined for all experimental animals, while for the handled animals behavioural parameters and changes were recorded daily and per animal. On average the handled and non-handled rabbits took the same amount of food per week, although there were large individual differences. The handled animals showed some behavioural adaptation to being handled. Handling had no influence on atherosclerosis size; this latter measure was only roughly determined by the amount of CHOL food eaten.

  10. Atherosclerosis and Cancer; A Resemblance with Far-reaching Implications.

    Science.gov (United States)

    Tapia-Vieyra, Juana Virginia; Delgado-Coello, Blanca; Mas-Oliva, Jaime

    2017-01-01

    Atherosclerosis and cancer are chronic diseases considered two of the main causes of death all over the world. Taking into account that both diseases are multifactorial, they share not only several important molecular pathways but also many ethiological and mechanistical processes from the very early stages of development up to the advanced forms in both pathologies. Factors involved in their progression comprise genetic alterations, inflammatory processes, uncontrolled cell proliferation and oxidative stress, as the most important ones. The fact that external effectors such as an infective process or a chemical insult have been proposed to initiate the transformation of cells in the artery wall and the process of atherogenesis, emphasizes many similarities with the progression of the neoplastic process in cancer. Deregulation of cell proliferation and therefore cell cycle progression, changes in the synthesis of important transcription factors as well as adhesion molecules, an alteration in the control of angiogenesis and the molecular similarities that follow chronic inflammation, are just a few of the processes that become part of the phenomena that closely correlates atherosclerosis and cancer. The aim of the present study is therefore, to provide new evidence as well as to discuss new approaches that might promote the identification of closer molecular ties between these two pathologies that would permit the recognition of atherosclerosis as a pathological process with a very close resemblance to the way a neoplastic process develops, that might eventually lead to novel ways of treatment. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  11. Atomic Force Microscopy Study of Atherosclerosis Progression in Arterial Walls.

    Science.gov (United States)

    Timashev, Peter S; Kotova, Svetlana L; Belkova, Galina V; Gubar'kova, Ekaterina V; Timofeeva, Lidia B; Gladkova, Natalia D; Solovieva, Anna B

    2016-04-01

    Cardiovascular disease remains the leading cause of mortality worldwide. Here we suggest a novel approach for tracking atherosclerosis progression based on the use of atomic force microscopy (AFM). Using AFM, we studied cross-sections of coronary arteries with the following types of lesions: Type II-thickened intima; Type III-thickened intima with a lipid streak; Type IV-fibrotic layer over a lipid core; Type Va-unstable fibrotic layer over a lipid core; Type Vc-very thick fibrotic layer. AFM imaging revealed that the fibrotic layer of an atherosclerotic plaque is represented by a basket-weave network of collagen fibers and a subscale network of fibrils that become looser with atherosclerosis progression. In an unstable plaque (Type Va), packing of the collagen fibers and fibrils becomes even less uniform than that at the previous stages, while a stable fibrotic plaque (Vc) has significantly tighter packing. Such alterations of the collagen network morphology apparently, led to deterioration of the Type Va plaque mechanical properties, that, in turn, resulted in its instability and propensity to rupture. Thus, AFM may serve as a useful tool for tracking atherosclerosis progression in the arterial wall tissue.

  12. Plasma IL-5 concentration and subclinical carotid atherosclerosis

    Science.gov (United States)

    Silveira, Angela; McLeod, Olga; Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Deleskog, Anna; Persson, Jonas; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Gustafsson, Sven; Söderberg, Stefan; Öhrvik, John; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Hamsten, Anders

    2015-01-01

    Objective Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). Methods We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. Results IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. Conclusions Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease. PMID:25587992

  13. Relation between Birth Weight, Growth, and Subclinical Atherosclerosis in Adulthood

    Science.gov (United States)

    Valente, Maria Helena; Gomes, Filumena Maria da Silva; Benseñor, Isabela Judith Martins; Brentani, Alexandra Valéria Maria; Escobar, Ana Maria de Ulhôa; Grisi, Sandra J. F. E.

    2015-01-01

    Background and Objectives. Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. This paper aims to study the relation between birthweight, growth in the first year of life, and subclinical atherosclerosis in adults. Methods. 88 adults aged between 20 and 31 were submitted to sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, and evaluation of subclinical atherosclerosis. Results. Birthweight 75th percentile (RC = −0.242, 95% CI [−0.476, −0.008] P 3,500 g was associated with (a) BMI >25.0 kg/m2, (RC = 0.317, 95% CI [0.782, 0.557] P 75th percentile (RC = 0.361, 95% CI [0.169, 0.552] P 75th percentile (RC = −0.253, 95% CI [−0.487, −0.018] P 75th percentile (RC = −0.241, 95% CI [−0.442, −0.041] P 3,500 g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all of them were related to subclinical atherosclerosis. PMID:25648854

  14. Association of obstructive sleep apnoea with subclinical coronary atherosclerosis.

    Science.gov (United States)

    Weinreich, Gerhard; Wessendorf, Thomas E; Erdmann, Timo; Moebus, Susanne; Dragano, Nico; Lehmann, Nils; Stang, Andreas; Roggenbuck, Ulla; Bauer, Marcus; Jöckel, Karl-Heinz; Erbel, Raimund; Teschler, Helmut; Möhlenkamp, Stefan

    2013-12-01

    Accumulating evidence suggests a role of obstructive sleep apnoea (OSA) as a risk factor for coronary atherosclerosis. This study aimed i) to assess the prevalence of OSA in the general population and ii) to analyse the association of this disorder with traditional cardiovascular disease risk factors and subclinical coronary atherosclerosis. In a cross-sectional analysis of the Heinz Nixdorf Recall study a subgroup of 1604 subjects (791 men, age 50-80 years) underwent OSA screening. Furthermore, coronary artery calcium (CAC) was measured. OSA was defined as apnoea-hypopnoea index (AHI) ≥ 15/h. OSA was observed in 29.1% of men and 15.6% of women. In a multiple linear regression analysis adjusted for risk factors AHI was associated with CAC in men aged ≤65 years (estimated log-transformed increase of CAC = 0.25, 95% confidence interval (CI) = -0.001-0.50, p = 0.051) and in women of any age (estimated log-transformed increase = 0.23, 95% CI = 0.04-0.41, p = 0.02). Doubling of the AHI was associated with a 19% increase of CAC in men aged ≤65 years and with a 17% increase in women of any age. In the general population aged ≥50 years OSA is associated with subclinical atherosclerosis in men aged ≤65 years and in women of any age, independent of traditional cardiovascular risk factors. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Influence of chronic exercise on carotid atherosclerosis in marathon runners.

    Science.gov (United States)

    Taylor, Beth A; Zaleski, Amanda L; Capizzi, Jeffrey A; Ballard, Kevin D; Troyanos, Christopher; Baggish, Aaron L; D'Hemecourt, Pierre A; Dada, Marcin R; Thompson, Paul D

    2014-02-14

    The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis. field study at Boston Marathon. 42 qualifiers (mean age±SD: 46±13 years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (46±12 years, n=21 women). We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10 years Framingham risk, central arterial stiffness and SBP and cIMT. Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p0.31) and were associated with age (all r≥0.41; p0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75 bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model. Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors.

  16. Differential associations of renal function with coronary and peripheral atherosclerosis.

    Science.gov (United States)

    Stamatelopoulos, Kimon S; Lekakis, John P; Tseke, Paraskevi; Ikonomidis, Ignatios; Kollias, George E; Alevizaki, Maria; Kanakakis, Ioannis; Voidonikola, Paraskevi; Zakopoulos, Nikolaos; Papamichael, Christos M

    2009-06-26

    The aim of this study was to examine the impact of renal dysfunction on both coronary and peripheral atherosclerosis in patients with coronary artery disease (CAD) without severe renal impairment. One hundred and eighty-seven consecutive patients referred for elective coronary angiography were enrolled. Mean IMT and the presence of plaques were measured in the carotid and femoral arteries prior to angiography as markers of subclinical peripheral atherosclerosis. The severity of CAD was evaluated by the Gensini score. Glomerular filtration rate (GFR) was estimated by the MDRD formula. Significant CAD (>50% stenosis) was identified in 139 patients. GFR independently correlated with the presence and severity of CAD with incremental value over that of IMT. Renal function was significantly but not independently correlated with carotid IMT in CAD patients. Femoral IMT and the presence of plaques did not show any significant correlations with GFR in patients with or without CAD. Renal function is an important predictor of the presence and severity of angiographic CAD in patients without severe renal impairment with incremental value over traditional risk factors for CAD and IMT. The contrasting weak or no associations of GFR with IMT and the presence of plaques suggest that renal dysfunction may exert differential effects on the development of coronary and peripheral atherosclerosis.

  17. [Prevention and treatment of atherosclerosis and cardiovascular diseases].

    Science.gov (United States)

    Knobler, Hilla; Bitzur, Rafael; Gavish, Dov; Rubinstein, Ardon; Henkin, Yaakov; Chajek-Shaul, Tova; Harats, Dror

    2012-05-01

    Atherosclerosis is one of the main causes of morbidity and mortality world-wide and specifically in Israel. These guidelines update the previous guidelines of the Israeli Society for Research, Prevention and Treatment of Atherosclerosis, published in 2005. The need for an update is based on new scientific data published in recent years necessitating changes in the recommendations for preventing and treating atherosclerosis. These guidelines were written in collaboration between all the societies outlined here and the content of this statement was approved by the delegates of these societies. The recommendations were written taking into consideration guidelines published by other international medical societies and also the specific needs of the Israeli medical system. Due to limitations of space, in the current paper we present: assessment of cardiovascular risk, smoking cessation and the treatment of dyslipidemia. Other sections including: recommendations to the general population, nutritional and physical activity recommendations, treatment of hypertension, prevention of ischemic stroke and the metabolic syndrome are available at http://www.ima.org.il/harefuah.

  18. Relation between Birth Weight, Growth, and Subclinical Atherosclerosis in Adulthood

    Directory of Open Access Journals (Sweden)

    Maria Helena Valente

    2015-01-01

    Full Text Available Background and Objectives. Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. This paper aims to study the relation between birthweight, growth in the first year of life, and subclinical atherosclerosis in adults. Methods. 88 adults aged between 20 and 31 were submitted to sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, and evaluation of subclinical atherosclerosis. Results. Birthweight 75th percentile (RC = −0.242, 95% CI [−0.476, −0.008] P3,500 g was associated with (a BMI >25.0 kg/m2, (RC = 0.317, 95% CI [0.782, 0.557] P75th percentile (RC = 0.361, 95% CI [0.169, 0.552] P75th percentile (RC = −0.253, 95% CI [−0.487, −0.018] P75th percentile (RC = −0.241, 95% CI [−0.442, −0.041] P3,500 g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all of them were related to subclinical atherosclerosis.

  19. Molecular characterization of Chlamydia pneumoniae associated to atherosclerosis.

    Science.gov (United States)

    Yazouli, Loubna El; Criscuolo, Alexis; Hejaji, Hicham; Bouaaza, Mohamed; Elmdaghri, Naima; Alami, Aziz Aroussi; Amraoui, Abderahim; Dakka, Nadia; Radouani, Fouzia

    2017-04-06

    Chlamydia pneumoniae is a respiratory pathogen associated with chronic inflammatory diseases such as asthma and atherosclerosis, and its detection in human carotid and coronary atheroma suggests some support for its involvement in atherogenesis. The main objective of our study was to evaluate the association between Chlamydia pneumoniae and atherosclerosis in Moroccan patients through a case/control approach and detected strain genotyping. A total of 137 cases and 124 controls were enrolled, nested PCR was performed for Chlamydia pneumoniae screening of the peripheral blood mononuclear cells (PBMCs) of both cases and controls as well as atheroma plaques from 37 cases, and positive samples were subjected to sequencing for genotyping and phylogenetic analysis. The results showed 54% and 18%, respectively, for positivity in cases and control PBMCs and 86.5% in atheroma plaques, the difference being significant between the two groups (pChlamydia pneumoniae in atherosclerosis in the studied population and genotyping revealed that detected strains were identical to human strains circulating worldwide. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

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    Waleska C. Dornas

    2010-08-01

    Full Text Available Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

  1. Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice.

    Science.gov (United States)

    Cazita, Patrícia M; Berti, Jairo A; Aoki, Carolina; Gidlund, Magnus; Harada, Lila M; Nunes, Valéria S; Quintão, Eder C R; Oliveira, Helena C F

    2003-01-01

    Reduced estrogen levels result in loss of protection from coronary heart disease in postmenopausal women. Enhanced and diminished atherosclerosis have been associated with plasma levels of cholesteryl ester transfer protein (CETP); however, little is known about the role of CETP-ovarian hormone interactions in atherogenesis. We assessed the severity of diet-induced atherosclerosis in ovariectomized (OV) CETP transgenic mice crossbred with LDL receptor knockout mice. Compared with OV CETP expressing ((+)), OV CETP non-expressing ((-)) mice had higher plasma levels of total, VLDL-, LDL-, and HDL-cholesterol, as well as higher antibodies titers against oxidized LDL. The mean aortic lesion area was 2-fold larger in OV CETP(-) than in OV CETP(+) mice (147 +/- 90 vs. 73 +/- 42 x 10(3) micro m(2), respectively). Estrogen therapy in OV mice blunted the CETP dependent differences in plasma lipoproteins, oxLDL antibodies, and atherosclerosis severity. Macrophages from OV CETP(+) mice took up less labeled cholesteryl ether (CEt) from acetyl-LDL than macrophages from OV CETP(-) mice. Estrogen replacement induced a further reduction in CEt uptake and an elevation in HDL mediated cholesterol efflux from pre-loaded OV CETP(+) as compared with OV CETP(-) macrophages. These findings support the proposed anti-atherogenic role of CETP in specific metabolic settings.

  2. Are AHSG polymorphisms directly associated with coronary atherosclerosis?

    Science.gov (United States)

    Muendlein, Axel; Stark, Nicole; Rein, Philipp; Saely, Christoph H; Geller-Rhomberg, Simone; Geiger, Kathrin; Vonbank, Alexander; Drexel, Heinz

    2012-01-18

    Fetuin-A (AHSG) has been proposed as a new cardiovascular risk factor. Fetuin-A levels as well as AHSG single nucleotide polymorphisms (SNPs) have been associated with intima media thickness and incident vascular events, respectively. However, the association between AHSG variants and angiographically determined coronary artery disease (CAD) has not been reported yet. Therefore, we aimed at investigating the association of AHSG SNPs with angiographically characterized coronary atherosclerosis. We genotyped AHSG variants rs4917, rs2248690, rs2518136, and rs2077119 in a cross-sectional study including 1,649 patients undergoing coronary angiography. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs2077119 deviates significantly from Hardy-Weinberg equilibrium and was excluded from further analysis. Neither under an additive, nor under a recessive or dominant model of inheritance, the association between investigated AHSG variants and angiographically determined CAD reached statistical significance. Haplotypes derived from these AHSG variants also were not significantly associated with coronary lesions. Further, no significant associations between investigated SNPs and the extent or severity of CAD could be observed (all p-values>0.05). Our data do not support a significant direct association between AHSG variants rs4917, rs2248690, and rs2518136 and clinical atherosclerosis as exemplified by angiographically characterized coronary atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. 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.

  4. The genesis of atherosclerosis and risk factors: a review.

    Science.gov (United States)

    Tegos, T J; Kalodiki, E; Sabetai, M M; Nicolaides, A N

    2001-02-01

    Atherosclerosis constitutes the most common medical and surgical problem. This can be manifested clinically as stroke, coronary artery disease, or peripheral vascular disease. In the present review the microscopic appearance of the normal arterial wall, the definition of atherosclerosis and the five theories of atherogenesis are described. These are: the lipid theory, the hemodynamic theory, the fibrin incrustation theory, the nonspecific mesenchymal hypothesis and the response to injury hypothesis. Based on the above theories the sequence of events in atherogenesis is analyzed. The classification of the atherosclerotic lesions according to Stary (types I-VI) and their characteristics appear in a table. The epidemiology and the role of the following risk factors are presented in detail: age, sex, lipid abnormalities, cigarette smoking, hypertension, diabetes mellitus, physical inactivity, alcohol consumption, obesity, and hemostatic factors. In addition, less common genetically determined associations like homocystinuria, Tangier disease, Hutchinson-Gilford syndrome (progeria), Werner's syndrome, radiation induced atherosclerosis and the implications of Chlamydia pneumoniae on the arterial wall are discussed.

  5. Effects of soy isoflavones on atherosclerosis: potential mechanisms.

    Science.gov (United States)

    Anthony, M S; Clarkson, T B; Williams, J K

    1998-12-01

    It has long been recognized that coronary heart disease rates are lower in Japan, where soy consumption is common, than in Western countries. In experimental studies, atherosclerosis was reduced in animals fed diets containing soy protein compared with those fed diets with animal protein. Recently, several lines of evidence have suggested that the components of soy protein that lower lipid concentrations are extractable by alcohol (eg, the isoflavones genistein and daidzein). We recently evaluated the relative effect of the soy protein versus the alcohol-extractable components of soy on cardiovascular disease and its risk factors. Young male and female cynomolgus monkeys were fed diets that contained either 1) casein-lactalbumin as the source of protein (casein), 2) soy protein isolate from which the isoflavones were alcohol extracted (SPI-), or 3) isoflavone-intact soy protein (SPI+). The SPI+ group had significant improvements in LDL cholesterol and HDL cholesterol. Only HDL cholesterol was significantly improved in the SPI- group males compared with the casein group. The casein group had the most atherosclerosis, the SPI+ group had the least, and the SPI- group was intermediate but did not differ significantly from the casein group. Potential mechanisms by which soy isoflavones might prevent atherosclerosis include a beneficial effect on plasma lipid concentrations, antioxidant effects, antiproliferative and antimigratory effects on smooth muscle cells, effects on thrombus formation, and maintenance of normal vascular reactivity.

  6. The role of fibroblast growth factor 21 in atherosclerosis.

    Science.gov (United States)

    Kokkinos, John; Tang, Shudi; Rye, Kerry-Anne; Ong, Kwok Leung

    2017-02-01

    The metabolic properties of the endocrine fibroblast growth factor 21 (FGF21) have been extensively studied in the past decade. Previous studies have demonstrated the lipid-lowering, anti-inflammatory and anti-oxidant properties of FGF21. FGF21 is mainly secreted in the liver and adipose tissue in response to a range of physiological and pathological stimuli. In animal and in vitro studies, FGF21 has been shown to improve lipid profiles and inhibit key processes in the pathogenesis of atherosclerosis. It exerts its effects on the cardiovascular system via adiponectin dependent and independent mechanisms. However, the signalling pathways by which FGF21 exerts its effects on endothelial cells remains unknown and needs to be further investigated. The elevation of circulating FGF21 levels in cardiovascular disease has also raised questions as to whether FGF21 can be used as a biomarker to predict subclinical atherosclerosis and cardiovascular events. Recent findings from population studies must be validated in independent cohorts before FGF21 can be used as a biomarker in the clinical setting. The anti-atherosclerotic effects of FGF21 have been investigated in two recent clinical trials, where treatment with an FGF21 analog significantly improved the cardiometabolic profile in obese patients with type 2 diabetes. This review will evaluate recent advances that suggest there may be a role for FGF21 in atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. DNA modifications in atherosclerosis: from the past to the future.

    Science.gov (United States)

    Borghini, Andrea; Cervelli, Tiziana; Galli, Alvaro; Andreassi, Maria Grazia

    2013-10-01

    The role of DNA damage in the pathogenesis of atherosclerosis has been extensively investigated in recent decades. There is now clear that oxidative stress is an important inducer of both DNA damage and telomere attrition which, in turn, can gives rise to genome instability and vascular senescence. This review discusses the role of the DNA damage response, including the key DNA repair pathways (base excision repair, nucleotide excision repair, homologous recombination and non-homologous end joining), deregulated cell cycle and apoptosis in atherosclerosis. We also highlight emerging evidence suggesting that epigenetic changes (DNA methylation and microRNA-mediated mechanisms), not associated with alterations in DNA sequences, may play a critical role in the regulation of the DNA damage response. Nevertheless, further investigation is still required to better understand the complexity of DNA repair and DNA damage response in atherosclerosis, making this topic an exciting and promising field for future investigation. Unraveling these molecular mechanisms provide the rationale for the development of novel efficient therapies to combat the vascular aging process. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. ARFI imaging for noninvasive material characterization of atherosclerosis.

    Science.gov (United States)

    Dumont, Douglas; Behler, Russell H; Nichols, Timothy C; Merricks, Elizabeth P; Gallippi, Caterina M

    2006-11-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States, with 70% of CVD mortalities the result of sequelae of atherosclerosis. An urgent need for enhanced delineation of vulnerable plaques has catalyzed the development of novel atherosclerosis imaging strategies that use X-ray computed tomography, magnetic resonance and ultrasound modalities. As suggested by the pathophysiology of plaque development and progression to vulnerability, insight to the focal material, i.e., mechanical, properties of arterial walls and plaques may enhance atherosclerosis characterization. We present acoustic radiation force impulse (ARFI) ultrasound in application to mechanically characterizing a raised focal atherosclerotic plaque in an iliac artery extracted from a relevant pig model. ARFI results are correlated to matched immunohistochemistry, indicating elastin and collagen composition. In regions of degraded elastin, slower recovery rates from peak ARFI-induced displacements were observed. In regions of collagen deposition, lower ARFI-induced displacements were achieved. This work demonstrates ARFI for characterizing the material nature of an atherosclerotic plaque.

  9. The programmatic hemosorption in the comprehensive treatment of atherosclerosis of various localization. Hemosorption in the treatment of atherosclerosis.

    Science.gov (United States)

    Markin, S S; Nalivaiko, E S; Khalilov, E M; Moreino, M S; Kaminka TYa; Fedin, A I; Teterina, E B; Belousov YuB

    1987-01-01

    The inclusion of hemosorption through activated coals into the comprehensive treatment of 580 patients sick with atherosclerosis has made it possible to achieve a positive clinical effect among 81 per cent of the patients sick with the ischemic heart disease, 79 per cent of atherosclerotic discirculatory encephalopathy and 76 per cent of obliterating atherosclerosis of lower limbs. The positive dynamics is especially visible among patients who are administered the programmatic hemosorption, making it possible over a long period of time (3-5 years) to sustain remission in the clinical state and the normal level of the lipids in the blood. The direct effect is expressed in the improved microcirculation, disappearance of the sludge-syndrome and the reduction of ischemic disorders. The remote effect of hemosorption is connected with the repeated removals of cholesterin of the atherogenic lipoproteids, which leads, we believe, to the interruption or even regression of the atherosclerotic process.

  10. The atherosclerosis burden score (ABS): a convenient ultrasound-based score of peripheral atherosclerosis for coronary artery disease prediction.

    Science.gov (United States)

    Yerly, Patrick; Marquès-Vidal, Pedro; Owlya, Reza; Eeckhout, Eric; Kappenberger, Lukas; Darioli, Roger; Depairon, Michèle

    2015-03-01

    Ultrasonographic detection of subclinical atherosclerosis improves cardiovascular risk stratification, but uncertainty persists about the most discriminative method to apply. In this study, we found that the "atherosclerosis burden score (ABS)", a novel straightforward ultrasonographic score that sums the number of carotid and femoral arterial bifurcations with plaques, significantly outperformed common carotid intima-media thickness, carotid mean/maximal thickness, and carotid/femoral plaque scores for the detection of coronary artery disease (CAD) (receiver operating characteristic (ROC) curve area under the curve (AUC) = 0.79; P = 0.027 to ABS was also more correlated with CAD extension (R = 0.55; P ABS was weakly correlated with the European Society of Cardiology chart risk categories (R(2) = 0.21), indicating that ABS provided information beyond usual cardiovascular risk factor-based risk stratification. Pending prospective studies on hard cardiovascular endpoints, ABS appears as a promising tool in primary prevention.

  11. Periodontal disease and carotid atherosclerosis: A meta-analysis of 17,330 participants.

    Science.gov (United States)

    Zeng, Xian-Tao; Leng, Wei-Dong; Lam, Yat-Yin; Yan, Bryan P; Wei, Xue-Mei; Weng, Hong; Kwong, Joey S W

    2016-01-15

    The association between periodontal disease and carotid atherosclerosis has been evaluated primarily in single-center studies, and whether periodontal disease is an independent risk factor of carotid atherosclerosis remains uncertain. This meta-analysis aimed to evaluate the association between periodontal disease and carotid atherosclerosis. We searched PubMed and Embase for relevant observational studies up to February 20, 2015. Two authors independently extracted data from included studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was assessed by the chi-squared test (Pperiodontal disease was associated with carotid atherosclerosis (OR: 1.27, 95% CI: 1.14-1.41; Pperiodontal disease was associated with carotid atherosclerosis; however, further large-scale, well-conducted clinical studies are needed to explore the precise risk of developing carotid atherosclerosis in patients with periodontal disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Under-expression of α8 integrin aggravates experimental atherosclerosis.

    Science.gov (United States)

    Menendez-Castro, Carlos; Cordasic, Nada; Neureiter, Daniel; Amann, Kerstin; Marek, Ines; Volkert, Gudrun; Stintzing, Sebastian; Jahn, Angelika; Rascher, Wolfgang; Hilgers, Karl F; Hartner, Andrea

    2015-05-01

    Integrins play an important role in vascular biology. The α8 integrin chain attenuates smooth muscle cell migration but its functional role in the development of atherosclerosis is unclear. Therefore, we studied the contribution of α8 integrin to atherosclerosis and vascular remodelling. We hypothesized that α8 integrin expression is reduced in atherosclerotic lesions, and that its under-expression leads to a more severe course of atherosclerosis. α8 Integrin was detected by immunohistochemistry and qPCR and α8 integrin-deficient mice were used to induce two models of atherosclerotic lesions. First, ligation of the carotid artery led to medial thickening and neointima formation, which was quantified in carotid cross-sections. Second, after crossing into ApoE-deficient mice, the formation of advanced vascular lesions with atherosclerotic plaques was quantified in aortic en face preparations stained with Sudan IV. Parameters of renal physiology and histopathology were assessed: α8 integrin was detected in the media of human and murine vascular tissue and was down-regulated in arteries with advanced atherosclerotic lesions. In α8 integrin-deficient mice (α8(-/-) ) as well as α8(+/-) and α8(+/+) littermates, carotid artery ligation increased media:lumen ratios in all genotypes, with higher values in ligated α8(-/-) and α8(+/-) compared to ligated α8(+/+) animals. Carotid artery ligation increased smooth muscle cell number in the media of α8(+/+) mice and, more prominently, of α8(-/-) or α8(+/-) mice. On an ApoE(-/-) background, α8(+/-) and α8(-/-) mice developed more atherosclerotic plaques than α8(+/+) mice. α8 Integrin expression was reduced in α8(+/-) animals. Renal damage with increased serum creatinine and glomerulosclerosis was detected in α8(-/-) mice only. Thus, under-expression of α8 integrin aggravates vascular lesions, while a complete loss of α8 integrin results in reduced renal mass and additional renal disease in the presence of

  13. Omega-3 fatty acid supplement prevents development of intracranial atherosclerosis.

    Science.gov (United States)

    Shen, Jiamei; Hafeez, Adam; Stevenson, James; Yang, Jianjie; Yin, Changbin; Li, Fengwu; Wang, Sainan; Du, Huishan; Ji, Xunming; Rafols, Jose A; Geng, Xiaokun; Ding, Yuchuan

    2016-10-15

    Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated the effect of omega-3 fatty acids (O3FA) in attenuating development of ICAS. Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6weeks. During the first 2weeks, NG-nitro-l-arginine methyl ester (l-NAME, 3mg/mL) was added to the drinking water of the high-cholesterol groups. The rats received supplementation with O3FA (5mg/kg/day) by gavages. Blood lipids including low density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG) and high density lipoprotein (HDL) were measured at 3 and 6weeks. The lumen of middle cerebral artery (MCA) and the thickness of the vessel wall were assessed. Inflammatory molecular markers were assessed by Western blot. A high-cholesterol diet exhibited a significant increase in the classic blood markers (LDL, CHO, and TG) for atherosclerosis, as well as a decrease in HDL. These markers were found to be progressively more severe with time. Lumen stenosis and intimal thickening were increased in MCA. O3FA showed attenuation of blood lipids with an absence of morphological changes. O3FA significantly reduced the inflammatory marker CD68 in MCA and prevented monocyte chemotactic protein (MCP-1) and interferon-γ (IFN-γ) expression in the brain. O3FA similarly decreased inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), markers affiliated with monocyte activity in atherosclerosis. Furthermore, O3FA significantly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), a marker for endothelial activation. Lastly, O3FA increased ATP-binding cassette transporter A1 (ABCA1) protein expression via

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

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    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

  15. Relationship between Chlamydia pneumonia and helicobacter pylori with atherosclerosis

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    ali Pooria

    2009-01-01

    Full Text Available Pooria A1, Maasoomi M2, Rafiee E3, Rezaee M4, Sabzi F5, Hossain Zadegan H6, Salehi M7, Mozaffari P8 1. Assistant Professor, Department of Surgery, Faculty of Medicine, Lorestan University of Medical Sciences 2. Professor, Department of Surgery, Faculty of Medicine, Kermanshah University of Medical Sciences, 3. Assistant Professor, Faculty of Medicine, Lorestan University of Medical Sciences, Department of Pathology 4. Associate Professor, Department of Surgery, Faculty of Medicine, Kermanshah University of Medical Sciences 5. Assistant Professor, Department of Statistics, Faculty of Health, Kermanshah University of Medical Sciences 6. Assistant Professor, Department of Microbiology, Faculty of Medicine, Lorestan University of Medical Sciences 7. Bsc in Nursing, Kermanshah University of Medical Sciences 8. Instructor, Department of Nursing, Faculty of Nursing and midwifery, Kermanshah University of Medical Sciences Abstract Background: Atherosclerosis is the most common cause of deaths in the developed countries and causes one million mortalities per year in the USA. Smoking, hypertension, diabetes, obesity, hyperlipidemia, stress, and low activity are known to be the causes of atherosclerosis. The objective of this study is to confirm the relationship between chlamydia pneumonia (Cpn, as well as helicobacter pylori (Hp and atherosclerosis. Materials and methods: In this analytical case-control study two groups of patients were studied. The first group including 30 patients over 30 years old with coronary artery disease were operated using coronary artery bypass graft. The control group included 30 persons assessed with angiography and having normal coronary arteries. The data were collected and analyzed using statistical methods. Results: The two groups were similar in terms of IgA and IgG anti-Cpn, and IgG anti- Hp but they were statistically different concerning IgA anti-Hp which had more positive cases in the case group in comparison with the

  16. Is there a consistent association between coronary heart disease and ischemic stroke caused by intracranial atherosclerosis?

    OpenAIRE

    Conforto, Adriana B.; Claudia da Costa Leite; Cesar H. Nomura; Edson Bor-Seng-Shu; Santos, Raul D

    2013-01-01

    Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke rec...

  17. Is there a consistent association between coronary heart disease and ischemic stroke caused by intracranial atherosclerosis?

    Science.gov (United States)

    Conforto, Adriana B; Leite, Claudia da Costa; Nomura, Cesar H; Bor-Seng-Shu, Edson; Santos, Raul D

    2013-05-01

    Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke recurrence and vascular death. More research and clinical trials are needed to answer whether early diagnosis of asymptomatic coronary heart disease and aggressive treatment can decrease the risk of vascular death in patients with ischemic stroke caused by intracranial atherosclerosis.

  18. Is there a consistent association between coronary heart disease and ischemic stroke caused by intracranial atherosclerosis?

    Directory of Open Access Journals (Sweden)

    Adriana B. Conforto

    2013-05-01

    Full Text Available Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke recurrence and vascular death. More research and clinical trials are needed to answer whether early diagnosis of asymptomatic coronary heart disease and aggressive treatment can decrease the risk of vascular death in patients with ischemic stroke caused by intracranial atherosclerosis.

  19. ATVB Distinguished Scientist Award: How Costimulatory and Coinhibitory Pathways Shape Atherosclerosis.

    Science.gov (United States)

    Ley, Klaus; Gerdes, Norbert; Winkels, Holger

    2017-05-01

    Immune cells play a critical role in atherosclerosis. Costimulatory and coinhibitory molecules of the tumor necrosis factor receptor and CD28 immunoglobulin superfamilies not only shape T-cell and B-cell responses but also have a major effect on antigen-presenting cells and nonimmune cells. Pharmacological inhibition or activation of costimulatory and coinhibitory molecules and genetic deletion demonstrated their involvement in atherosclerosis. This review highlights recent advances in understanding how costimulatory and coinhibitory pathways shape the immune response in atherosclerosis. Insights gained from costimulatory and coinhibitory molecule function in atherosclerosis may inform future therapeutic approaches. © 2017 American Heart Association, Inc.

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

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    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.

  1. [25 year experience with using surgical correction of dislipidemia in treatment of patients with atherosclerosis].

    Science.gov (United States)

    Sedov, V M; Mirchuk, K K; Sedletskiĭ, Iu I

    2011-01-01

    An analysis of results of using partial ileoshunting for the treatment of dislipidemia in 159 patients with atherosclerosis has shown that operation of partial ileoshunting has an obligatory, pronounced and lifelong lipidcorrecting effect. An antiatherogenic effect of the operation of partial ileoshunting is manifested as the improvement of the clinical course of the disease caused by atherosclerosis, by less number of thrombotic complications of atherosclerosis and less lethality from cardio-vascular diseases. At a longer follow-up period, the efficiency of partial ileoshunting as a means of secondary prophylactics of atherosclerosis is confirmed but in case of liquidation after operation of dislipoproteidemia.

  2. Chronic inflammation-enhanced atherosclerosis: can we consider it as a new clinical syndrome?

    Science.gov (United States)

    Kucharz, Eugene Joseph

    2012-03-01

    Incidence of cardiovascular disease in patients with chronic autoimmune disorder like rheumatoid arthritis is much higher than in general population. Cardiovascular events (e.g. myocardial infarction or stroke) are caused by premature accelerated development of atherosclerosis. Chronic inflammation-enhanced atherosclerosis syndrome is proposed as a separate syndrome occurring in patients suffering of chronic inflammation. It is suggested that atherosclerosis as an inflammatory disease and long-lasting extravascular inflammation have common mechanisms resulting in an increase in atherosclerosis and its sequellae, cardiovascular diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study.

    Science.gov (United States)

    Fernández-Friera, Leticia; Peñalvo, José L; Fernández-Ortiz, Antonio; Ibañez, Borja; López-Melgar, Beatriz; Laclaustra, Martín; Oliva, Belén; Mocoroa, Agustín; Mendiguren, José; Martínez de Vega, Vicente; García, Laura; Molina, Jesús; Sánchez-González, Javier; Guzmán, Gabriela; Alonso-Farto, Juan C; Guallar, Eliseo; Civeira, Fernando; Sillesen, Henrik; Pocock, Stuart; Ordovás, José M; Sanz, Ginés; Jiménez-Borreguero, Luis Jesús; Fuster, Valentín

    2015-06-16

    Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. 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% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01410318. © 2015 American Heart Association, Inc.

  4. 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.

  5. Effect of ACAT inhibition on the progression of coronary atherosclerosis.

    Science.gov (United States)

    Nissen, Steven E; Tuzcu, E Murat; Brewer, H Bryan; Sipahi, Ilke; Nicholls, Stephen J; Ganz, Peter; Schoenhagen, Paul; Waters, David D; Pepine, Carl J; Crowe, Tim D; Davidson, Michael H; Deanfield, John E; Wisniewski, Lisa M; Hanyok, James J; Kassalow, Laurent M

    2006-03-23

    The enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol in a variety of tissues. In some animal models, ACAT inhibitors have antiatherosclerotic effects. We performed intravascular ultrasonography in 408 patients with angiographically documented coronary disease. All patients received usual care for secondary prevention, including statins, if indicated. Patients were randomly assigned to receive the ACAT inhibitor pactimibe (100 mg per day) or matching placebo. Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. The primary efficacy variable analyzing the progression of atherosclerosis--the change in percent atheroma volume--was similar in the pactimibe and placebo groups (0.69 percent and 0.59 percent, respectively; P=0.77). However, both secondary efficacy variables assessed by means of intravascular ultrasonography showed unfavorable effects of pactimibe treatment. As compared with baseline values, the normalized total atheroma volume showed significant regression in the placebo group (-5.6 mm3, P=0.001) but not in the pactimibe group (-1.3 mm3, P=0.39; P=0.03 for the comparison between groups). The atheroma volume in the most diseased 10-mm subsegment regressed by 3.2 mm3 in the placebo group, as compared with a decrease of 1.3 mm3 in the pactimibe group (P=0.01). The combined incidence of adverse cardiovascular outcomes was similar in the two groups (P=0.53). For patients with coronary disease, treatment with an ACAT inhibitor did not improve the primary efficacy variable (percent atheroma volume) and adversely affected two major secondary efficacy measures assessed by intravascular ultrasonography. ACAT inhibition is not an effective strategy for limiting atherosclerosis and may promote atherogenesis. (ClinicalTrials.gov number, NCT00268515.). Copyright 2006 Massachusetts Medical Society.

  6. Sleep Characteristics and Carotid Atherosclerosis Among Midlife Women.

    Science.gov (United States)

    Thurston, Rebecca C; Chang, Yuefang; von Känel, Roland; Barinas-Mitchell, Emma; Jennings, J Richard; Hall, Martica H; Santoro, Nanette; Buysse, Daniel J; Matthews, Karen A

    2017-02-01

    Midlife, which encompasses the menopause transition in women, can be a time of disrupted sleep and accelerated atherosclerosis accumulation. Short or poor sleep quality has been associated with cardiovascular disease (CVD) risk; few studies have investigated relations among midlife women. We tested whether shorter actigraphy sleep time or poorer subjective sleep quality was associated with carotid atherosclerosis among midlife women. Two hundred fifty-six peri- and postmenopausal women aged 40-60 years completed 3 days of wrist actigraphy, hot flash monitoring, questionnaires (Pittsburgh Sleep Quality Index [PSQI], Berlin), a blood draw, and carotid ultrasound [intima media thickness (IMT), plaque]. Associations of objective (actigraphy) and subjective (PSQI) sleep with IMT/plaque were tested in regression models (covariates: age, race, education, body mass index, blood pressure, lipids, insulin resistance, medications, snoring, depressive symptoms, sleep hot flashes, and estradiol). Shorter objective sleep time was associated with higher odds of carotid plaque (for each hour shorter sleep, plaque score ≥ 2, odds ratio (OR) [95% confidence interval, CI] = 1.58 [1.11-2.27], p = .01; plaque score = 1, OR [95% CI] = 0.95 [0.68-1.32], p = .75, vs. no plaque, multivariable). Poorer subjective sleep quality was associated with higher mean IMT [β, b (standard error, SE) = 0.004 (0.002), p = .03], maximal IMT [b (SE) = 0.009 (0.003), p = .005], and plaque [plaque score ≥ 2, OR (95% CI) = 1.23 (1.09-1.40), p = .001; score = 1, OR (95% CI) = 1.06 (0.93-1.21), p = .37, vs. no plaque] in multivariable models. Findings persisted additionally adjusting for sleep hot flashes and estradiol. Shorter actigraphy-assessed sleep time and poorer subjective sleep quality were associated with increased carotid atherosclerosis among midlife women. Associations persisted adjusting for CVD risk factors, hot flashes, and estradiol.

  7. Characteristics and Outcomes of Vertebrobasilar Artery Dissection with Accompanied Atherosclerosis

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    Chun Chien

    2017-10-01

    Full Text Available Background: With the popularity of MRI use, vertebrobasilar artery dissection (VBD has been found more frequently in patients with posterior circulation ischemic stroke (PCS. The relationship between VBD and atherosclerosis is unknown. The present study aimed to prove the hypothesis that PCS with pure VBD (p-VBD and with VBD and accompanied cervical or cerebral artery atherosclerosis (a-VBD have distinct manifestations. Methods: Patients with VBD-related PCS who were prospectively enrolled in the Taipei Veterans General Hospital Stroke Registry between January 1, 2010 and August 31, 2014 were recruited for the present study. Patients who had (1 atherosclerotic plaques with or without stenotic flow in cervical arteries on Duplex ultrasonography or (2 focal >30% stenosis in cerebral arteries other than the dissecting region (usually in arterial bifurcations which are prone to atheroma formation on brain MRA were defined as a-VBD. Results: There were 91 patients (67 [73.6%] males, mean age 65.5 years [SD = 15.2, range, 21–91] with VBD-related PCS recruited for the present study; 31 were a-VBD and 60 were p-VBD. The results showed that there were significant differences in onset age, frequency of cigarette smoking, dissecting vascular involvement, and infarct locations between the 2 groups. In addition, compared with p-VBD, the a-VBD group had poorer functional recovery at 3 months and 1 year, respectively, which was independent of age, sex, vascular risk factors, stroke severity at admission, and treatment options. Conclusion: VBD-related PCS with and without accompanied atherosclerosis had different manifestations and should be regarded as distinct arterial diseases.

  8. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Atherosclerosis and transit of HDL through the lymphatic vasculature.

    Science.gov (United States)

    Martel, Catherine; Randolph, Gwendalyn J

    2013-09-01

    Key components of atherosclerotic plaque known to drive disease progression are macrophages and cholesterol. It has been widely understood, and bolstered by recent evidence, that the efflux of cholesterol from macrophage foam cells quells disease progression or even to promote regression. Following macrophage cholesterol efflux, cholesterol loaded onto HDL must be removed from the plaque environment. Here, we focus on recent evidence that the lymphatic vasculature is critical for the removal of cholesterol, likely as a component of HDL, from tissues including skin and the artery wall. We discuss the possibility that progression of atherosclerosis might in part be linked to sluggish removal of cholesterol from the plaque.

  10. The Canadian Atherosclerosis Society--history and present status.

    Science.gov (United States)

    Haust, M D

    1991-10-01

    Since its inception in 1983 the Canadian Atherosclerosis Society (CAS) has established itself firmly on the national and international scene as a forceful scientific voice. Its presence and activities have had their dominant expression at annual meetings held jointly with the Royal College of Physicians and Surgeons of Canada (RCPSC) and the Canadian Society for Clinical Investigation (CSCI) and in sponsoring other scientific and educational events, the most important of which was the Canadian Consensus Conference on Cholesterol (Ottawa, March 1988). It provided a forum for interaction between the scientific community, government, funding agencies, industry and the general public, and culminated in concrete recommendations for the populace of Canada. It also 'induced' a continuum in governmental and public concern for health with respect to atherosclerosis, and beyond it, the field of cardiovascular diseases. This dialogue continues. As a member (Constituent Society) of the International Atherosclerosis Society (IAS), the CAS has a voice in the international community, its policies and activities. The membership increase from 69 in 1983 to 175 in 1991 reflects steady growth of the CAS. The Society has been active in other areas (publications, awards for young investigators, and common educational endeavours with other groups) and will be host to the 1994 International Symposium on Atherosclerosis. Over a short period of only eight years, all of the above attests to sufficient progress (or achievement) for any scientific society. And yet, there remain quite a few areas not addressed as yet and some sad experiences (eg, that with the Long Term Planning Committee) that must be quickly remedied, if the Society is to keep pace with the everchanging emphasis in research that in the final analysis aims at improving the overall well-being and health of all Canadians. Inherent in the definition of history is the premise that accounts be provided of facts only. Historians

  11. Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Tomoko Kurita-Ochiai

    2015-09-01

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

  12. [Determination of the intelligence quotient of pilots with incipient atherosclerosis].

    Science.gov (United States)

    Krapivnitskaia, T A

    2006-01-01

    Comprehensive examination, including clinical-functional and psychological testing, was given to 189 essentially healthy civil pilots and 235 pilots with atherosclerosis of aorta and trunks without considerable blood flow disturbance. The total of 835 investigations was performed. Distribution into health groups was conducted on clinical diagnosis. Pilots with cardiovascular pathologies were found to have the intelligence quotient significantly lowered. Associated clinical and psychological tests were effective in revealing and dynamic monitoring of incipient diseases, and taking reasoned disposition regarding pilot's fitness for flight duties.

  13. Cholesterol vehicle in experimental atherosclerosis 24: avocado oil.

    Science.gov (United States)

    Kritchevsky, David; Tepper, Shirley A; Wright, Scott; Czarnecki, Susanne K; Wilson, Thomas A; Nicolosi, Robert J

    2003-02-01

    To determine atherogenicity of avocado oil relative to saturated (coconut oil), monounsaturated (olive oil) and polyunsaturated (corn oil) fats. New Zealand White rabbits were fed a semipurified diet containing 0.2% cholesterol and 14% fat for 90 days. They were then necropsied and severity of atherosclerosis was determined visually. Coconut oil was the most atherogenic fat. Corn oil was only slightly less atherogenic than either olive or avocado oils. Percentage of serum HDL cholesterol was highest in the rabbits fed the two monounsaturated fats. Avocado oil is of the same order of atherogenicity as corn oil and olive oil.

  14. Imaging Techniques for Diagnosis of Thoracic Aortic Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Wouter W. Jansen Klomp

    2016-01-01

    Full Text Available The most severe complications after cardiac surgery are neurological complications including stroke which is often caused by emboli merging from atherosclerosis in the ascending aorta to the brain. Information about the thoracic aorta is crucial in reducing the embolization risk for both surgical open and closed chest procedures such as transaortic heart valve implantation. Several techniques are available to screen the ascending aorta, for example, transesophageal echocardiography (TEE, epiaortic ultrasound, TEE A-view method, manual palpation, computed tomography, and magnetic resonance imaging. This paper provides a description of the advantages and disadvantages of these imaging techniques.

  15. Imaging Techniques for Diagnosis of Thoracic Aortic Atherosclerosis

    Science.gov (United States)

    Jansen Klomp, Wouter W.; Brandon Bravo Bruinsma, George J.; van 't Hof, Arnoud W.; Grandjean, Jan. G.; Nierich, Arno P.

    2016-01-01

    The most severe complications after cardiac surgery are neurological complications including stroke which is often caused by emboli merging from atherosclerosis in the ascending aorta to the brain. Information about the thoracic aorta is crucial in reducing the embolization risk for both surgical open and closed chest procedures such as transaortic heart valve implantation. Several techniques are available to screen the ascending aorta, for example, transesophageal echocardiography (TEE), epiaortic ultrasound, TEE A-view method, manual palpation, computed tomography, and magnetic resonance imaging. This paper provides a description of the advantages and disadvantages of these imaging techniques. PMID:26966580

  16. Data on atherosclerosis specific antibody conjugation to nanoemulsions

    Directory of Open Access Journals (Sweden)

    Geoffrey Prévot

    2017-12-01

    Full Text Available This article present data related to the publication entitled “Iron oxide core oil-in-water nanoemulsion as tracer for atherosclerosis MPI and MRI imaging” (Prévot et al., 2017 [1]. Herein we describe the engineering in the baculovirus-insect cell system and purification processes of the human scFv-Fc TEG4-2C antibody, specific of platelets within the atheroma plaque. For molecular targeting purpose, atheroma specific antibody was conjugated to nanoemulsions (NEs using a heterobifunctional linker (DSPE-PEG-maleimide. Atheroma labelling was assayed by immunochemistry on arterial sections from rabbits.

  17. A Combined Approach to Severe Multi-Organ Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Habibollah Saadat

    2009-03-01

    Full Text Available Severe coronary artery disease often coexists with peripheral vascular atherosclerosis. The assessment of the supra-aortic circulation is, therefore, of clinical relevance. We herein describe a case of coronary artery disease treated with surgical revascularization using the internal mammary artery and thereafter the progressive atherosclerotic disease of the native coronary arteries as well as the left subclavian and left renal arteries. We also describe and discuss the clinical presentation, the diagnostic procedures, and the therapeutic approach with respect to the percutaneous transluminal angioplasty of the subclavian, renal, and right coronary arteries.

  18. Prevalence and long-term clinical significance of intracranial atherosclerosis after ischaemic stroke or transient ischaemic attack

    DEFF Research Database (Denmark)

    Ovesen, Christian; Abild, Annemette; Christensen, Anders Fogh

    2013-01-01

    We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation.......We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation....

  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.

    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. White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls

    DEFF Research Database (Denmark)

    Devantier, Torben Albert; Nørgaard, Bjarne Linde; Poulsen, Mikael Kjær

    2016-01-01

    Background: Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be importa...

  1. 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

    of this approach for creating atherosclerosis models also in nonmurine species was demonstrated by inducing hypercholesterolemia and early atherosclerosis in Golden Syrian hamsters. CONCLUSIONS: Single injections of proprotein convertase subtilisin/kexin type 9-encoding recombinant adeno-associated viral vectors...

  2. Heat-killed Staphylococcus aureus reduces atherosclerosis by inducing anti-inflammatory macrophages

    NARCIS (Netherlands)

    Frodermann, V.; van Duijn, J.; van Puijvelde, G. H. M.; van Santbrink, P. J.; Lagraauw, H. M.; de Vries, Margreet R; Quax, P. H. A.; Bot, I.; Foks, A. C.; de Jager, S. C. A.; Kuiper, J.

    Background Staphylococcus aureus cell wall components can induce IL-10 responses by immune cells, which may be atheroprotective. Therefore, in this study, we investigated whether heat-killed S. aureus (HK-SA) could inhibit the development of atherosclerosis. Methods Atherosclerosis-susceptible LDL

  3. Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis

    NARCIS (Netherlands)

    Gareus, Ralph; Kotsaki, Elena; Xanthoulea, Sofia; van der Made, Ingeborg; Gijbels, Marion J. J.; Kardakaris, Rozina; Polykratis, Apostolos; Kollias, George; de Winther, Menno P. J.; Pasparakis, Manolis

    2008-01-01

    Atherosclerosis is a progressive disorder of the arterial wall and the underlying cause of cardiovascular diseases such as heart attack and stroke. Today, atherosclerosis is recognized as a complex disease with a strong inflammatory component. The nuclear factor-kappaB (NF-kappaB) signaling pathway

  4. Early Detection of Subclinical Atherosclerosis in Asymptomatic Patients Assessed by Carotid Duplex and Coronary Computed Tomography

    Directory of Open Access Journals (Sweden)

    Cheng-Hsi Chen

    2013-03-01

    Conclusion: Carotid duplex may detect subclinical vascular atherosclerosis in more than half of asymptomatic patients without coronary artery calcification detected by coronary computed tomography. These findings have important implications for early-stage atherosclerosis screening and implementation of primary preventive intervention.

  5. Study of early atherosclerosis in juvenile-onset systemic lupus erythematosus patients

    Directory of Open Access Journals (Sweden)

    Emtethal A Said Ahmed

    2017-01-01

    Conclusion In patients with jSLE, some traditional and nontraditional risk factors such as increased low-density lipoprotein, triglycerides, total cholesterol, BMI, fasting blood sugar, and proteinuria for the development of subclinical atherosclerosis were identified. It is likely that good disease control is the optimum way to prevent premature atherosclerosis in jSLE.

  6. Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

    Science.gov (United States)

    Ruscitti, Piero; Cipriani, Paola; Masedu, Francesco; Romano, Silvio; Berardicurti, Onorina; Liakouli, Vasiliki; Carubbi, Francesco; Di Benedetto, Paola; Alvaro, Saverio; Penco, Maria; Valenti, Marco; Giacomelli, Roberto

    2017-01-01

    Several studies showed the close relationship between Rheumatoid Arthritis (RA) and cerebro-cardiovascular events (CVEs) and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV) and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis. We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis. We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH), type 2 diabetes mellitus and metabolic syndrome (MS), at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis. Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

  7. Relation of Framingham Risk Score to Subclinical Atherosclerosis Evaluated Across Three Arterial Sites

    Science.gov (United States)

    Karim, Roksana; Hodis, Howard N; Detrano, Robert; Liu, Chao-ran; Liu, Chi-hua; Mack, Wendy J

    2008-01-01

    The Framingham risk score (FRS) is widely used in clinical practice to identify subjects at high risk for developing coronary heart disease (CHD). However, FRS may not accurately identify subjects at risk. We measured subclinical atherosclerosis in the coronary arteries and aorta with the presence of calcium (CAC and AC, respectively) and in the common carotid artery by intima-media thickness (CIMT) in 498 healthy subjects. The distribution of these subclinical atherosclerosis measures was evaluated across 3 strata of the FRS. CAC, AC and CIMT were significantly independently associated with FRS. The FRS increased with the number of arterial sites with atherosclerosis. Sixty-nine percent of the subjects categorized in the low risk group (FRS20%) had 1 or more vascular imaging studies demonstrating subclinical atherosclerosis. Among the low risk group, subjects with atherosclerosis had a longer history of lifetime smoking compared to those without atherosclerosis. In conclusion, subclinical atherosclerosis is prominent across the spectrum of FRS. Evaluation of subclinical atherosclerosis in different arterial sites in addition to FRS may be useful in targeting subjects for lifestyle and other interventions. PMID:18805105

  8. Identifying novel genes for atherosclerosis through mouse-human comparative genetics

    NARCIS (Netherlands)

    Wang, XS; Ishimori, N; Korstanje, R; Rollins, J; Paigen, B

    Susceptibility to atherosclerosis is determined by both environmental and genetic factors. Its genetic determinants have been studied by use of quantitative- trait - locus ( QTL) analysis. So far, 21 atherosclerosis QTLs have been identified in the mouse: 7 in a high- fat - diet model only, 9 in a

  9. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-01-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This

  10. Atherosclerosis and ischemic cardiomyopathy in a captive, adult red-tailed hawk (Buteo jamaicensis).

    Science.gov (United States)

    Shrubsole-Cockwill, Alana; Wojnarowicz, Chris; Parker, Dennilyn

    2008-09-01

    An adult, male, captive red-tailed hawk (Buteo jamaicensis) of at least 19 years of age presented in dorsal recumbency. The hawk was nonresponsive, and despite initial supportive care, died shortly after presentation. Gross postmortem revealed no abnormal findings. Histologic examination demonstrated atherosclerosis and ischemic cardiomyopathy. This is the first reported case of atherosclerosis in a red-tailed hawk.

  11. 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...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

  12. The dark side of innate immune memory: the development of atherosclerosis

    NARCIS (Netherlands)

    Bekkering, S.

    2017-01-01

    Cardiovascular diseases, specifically atherosclerosis, are the leading cause of death worldwide. In the Netherlands alone, each year 100 people die from atherosclerosis. It is important to better understand the progression of this disease. In the last 15 years, the role of inflammation and the

  13. Sudden Cardiac Death in Young Adults: Environmental Risk Factors and Genetic Aspects of Premature Atherosclerosis*(,) †

    DEFF Research Database (Denmark)

    Larsen, Maiken K; Nissen, Peter H; Kristensen, Ingrid B

    2012-01-01

    pathogenic mutations. Lipid profiles and genetic testing for FH could be considered when autopsy reveals significant atherosclerosis of the coronary arteries in young adults. First-degree family members are advised to seek medical advice and testing to determine their own risks of atherosclerosis to prevent...

  14. 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...

  15. Association of Endothelial and Oxidative Stress with Metabolic Syndrome and Subclinical Atherosclerosis: Multi-Ethnic Study of Atherosclerosis

    Science.gov (United States)

    Vaidya, Dhananjay; Szklo, Moyses; Cushman, Mary; Holvoet, Paul; Polak, Joseph; Bahrami, Hossein; Jenny, Nancy Swords; Ouyang, Pamela

    2011-01-01

    Objectives A cluster of metabolic abnormalities termed metabolic syndrome (MetS) is associated with vascular endothelial dysfunction and oxidative internal milieu. We examined whether the association of MetS with subclinical atherosclerosis is explained by biomarkers of endothelial damage and oxidative stress. Methods MESA is a population based study of 45-84 year old individuals of four US ethnicities without clinical cardiovascular disease. A random sample of 997 MESA participants had data on the following biomarkers: von Willebrand Factor, soluble intercellular adhesion molecule-1 (sICAM1), CD40 ligand, soluble thrombomodulin, E-selectin, and oxidized LDL (oxLDL). We examined whether the associations of MetS with B-mode ultrasound-defined common and internal carotid intimal medial thickness (IMT) and coronary artery calcium (CAC) measured using computerized tomography were explained by the biomarkers using multiple regression methods. Results MetS was associated with higher levels of each of the biomarkers (psubclinical atherosclerosis remained unchanged after adjustment for the biomarkers. After adjusting for MetS, oxLDL was suggestively associated with greater prevalence of detectable CAC (p=0.005) and thicker internal carotid IMT (p=0.002), while sICAM-1was significantly associated with greater prevalence of detectable CAC (p=0.001). Conclusions The association of MetS with subclinical atherosclerosis was independent of its association with biomarkers of endothelial damage and oxidative stress, suggesting that metabolic abnormalities and oxidative endothelial damage may lead to atherosclerotic disease through distinct mechanisms. PMID:21505504

  16. Association of Rheumatoid Factors With Subclinical and Clinical Atherosclerosis in African American Women: The Multiethnic Study of Atherosclerosis.

    Science.gov (United States)

    Majka, Darcy S; Vu, Thanh-Huyen T; Pope, Richard M; Teodorescu, Marius; Karlson, Elizabeth W; Liu, Kiang; Chang, Rowland W

    2017-02-01

    Although the association between rheumatoid arthritis (RA) and cardiovascular disease (CVD) is established, the exact mechanism is unknown. We tested the hypothesis that RA-related autoantibodies are independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events. The Multi-Ethnic Study of Atherosclerosis (MESA) is a community-based cohort study prospectively collecting CVD outcome and risk factor data in middle-aged to elderly multiethnic participants since 2000. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP2) by enzyme-linked immunosorbent assay, and coronary artery calcium (CAC) by computed tomography, were measured at MESA baseline in 6,532 participants who were followed for 10.3 years for coronary heart disease (CHD) end points (myocardial infarction, cardiac arrest, CHD death) and CVD end points (included CHD end points, stroke, stroke death). Multivariable logistic regression and Cox regression assessed associations between RF/anti-CCP and CAC or CVD end points. IgM RF, IgA RF, anti-CCP, and either RF isotype predictors were positive in 15.8%, 8.7%, 2.0%, and 20.6%, respectively. A total of 12.2% had CAC ≥300, 7.1% had CHD end points, and 10.2% had CVD end points. IgA RF and anti-CCP were associated with CAC ≥300 in African American women (odds ratio [OR] 2.4 [95% confidence interval (95% CI) 1.2-5.1] and OR 4.1 [95% CI 1.3-12.7], respectively). RA-related autoantibodies were also associated with clinical CVD events in African American women (anti-CCP: OR 5.3 [95% CI 2.4-12.0]; either RF isotype: OR 2.4 [95% CI 1.4-4.0]). There was a trend for association between autoantibodies and CAC in white women. No associations were found in men. RA-related autoantibodies are associated with subclinical and clinical atherosclerosis in African American women from a community-based non-RA cohort, indicating autoimmune factors may play a role in the pathogenesis of atherosclerosis. © 2016, American

  17. Traditional Chinese Medicine Protects against Cytokine Production as the Potential Immunosuppressive Agents in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yan Ren

    2017-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a critical factor at all stages of atherosclerosis progression. Proinflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. Accordingly, strategies to inhibit immune activation and impede immune responses towards anti-inflammatory activity are an alternative therapeutic strategy to conventional chemotherapy on cardiocerebrovascular outcomes. Since a number of Chinese medicinal plants have been used traditionally to prevent and treat atherosclerosis, it is reasonable to assume that the plants used for such disease may suppress the immune responses and the resultant inflammation. This review focuses on plants that have immunomodulatory effects on the production of inflammatory cytokine burst and are used in Chinese traditional medicine for the prevention and therapy of atherosclerosis.

  18. 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.

  19. Subclinical atherosclerosis in patients with recurrent aphthous stomatitis.

    Science.gov (United States)

    Sereflican, M; Sereflican, B; Dagistan, E; Goksugur, N; Kizildag, B

    2016-09-01

    Recurrent aphtous stomatitis (RAS) is an inflammatory oral mucosal disease. It has been known that inflammatory cascade plays important role in the atherosclerotic process. The aim of the study was to investigate the relationship between subclinical atherosclerotic findings and a systemic inflammatory disease, RAS. In total, 32 patients with RAS were matched with 30 control subjects on the basis of age, sex, and major cardiovascular risk factors. Laboratory parameters including lipid profiles were determined for patients and controls. B-mode ultrasonography was used to assess carotid extra-medial thickness (cEMT) and carotid intima-media thickness (cIMT). Both cEMT and cIMT in the RAS group were significantly higher than in the control group (P = 0.002 and 0.013, respectively). There was a significant positive correlation between cIMT and cEMT (r = 0.381, P = 0.034). cIMT was positively correlated with age, triglyceride levels, and systolic blood pressure, while cEMT was positively correlated with age in patients with RAS. To our knowledge, this is the first reported study to evaluate cEMT and cIMT in patients with RAS. This study presents morphological evidence of subclinical atherosclerosis in patients with RAS. Further studies investigating the relationship between atherosclerosis and RAS are needed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model.

    Science.gov (United States)

    Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

    2015-01-01

    To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Losartan can alleviate experimental atherosclerosis induced by hyperuricemia.

  1. Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis.

    Science.gov (United States)

    van der Valk, Fleur M; Schulte, Dominik M; Meiler, Svenja; Tang, Jun; Zheng, Kang He; Van den Bossche, Jan; Seijkens, Tom; Laudes, Matthias; de Winther, Menno; Lutgens, Esther; Alaarg, Amr; Metselaar, Josbert M; Dallinga-Thie, Geesje M; Mulder, Willem J M; Stroes, Erik S G; Hamers, Anouk A J

    2016-08-01

    Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we confirmed in low-density lipoprotein receptor knockout (LDLr(-/-)) mice that LN-PLP accumulates in plaque macrophages. Next, we found that LN-PLP infusions at 10mg/kg for 2weeks enhanced monocyte recruitment to plaques. In follow up, after 6weeks of LN-PLP exposure we observed (i) increased macrophage content, (ii) more advanced plaque stages, and (iii) larger necrotic core sizes. Finally, in vitro studies showed that macrophages become lipotoxic after LN-PLP exposure, exemplified by enhanced lipid loading, ER stress and apoptosis. These findings indicate that liposomal prednisolone may paradoxically accelerate atherosclerosis by promoting macrophage lipotoxicity. Hence, future (nanomedicinal) drug development studies are challenged by the multifactorial nature of atherosclerotic inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Estrogens and atherosclerosis: insights from animal models and cell systems.

    Science.gov (United States)

    Nofer, Jerzy-Roch

    2012-04-01

    Estrogens not only play a pivotal role in sexual development but are also involved in several physiological processes in various tissues including vasculature. While several epidemiological studies documented an inverse relationship between plasma estrogen levels and the incidence of cardiovascular disease and related it to the inhibition of atherosclerosis, an interventional trial showed an increase in cardiovascular events among postmenopausal women on estrogen treatment. The development of atherosclerotic lesions involves complex interplay between various pro- or anti-atherogenic processes that can be effectively studied only in vivo in appropriate animal models. With the advent of genetic engineering, transgenic mouse models of atherosclerosis have supplemented classical dietary cholesterol-induced disease models such as the cholesterol-fed rabbit. In the last two decades, these models were widely applied along with in vitro cell systems to specifically investigate the influence of estrogens on the development of early and advanced atherosclerotic lesions. The present review summarizes the results of these studies and assesses their contribution toward better understanding of molecular mechanisms underlying anti- and/or pro-atherogenic effects of estrogens in humans.

  3. Stroke Caused by Atherosclerosis of the Major Intracranial Arteries.

    Science.gov (United States)

    Banerjee, Chirantan; Chimowitz, Marc I

    2017-02-03

    Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and intracranial atherosclerosis. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics, and Asians compared with whites. Diabetes mellitus, hypertension, metabolic syndrome, smoking, hyperlipidemia, and a sedentary lifestyle are the major modifiable risk factors associated with intracranial atherosclerotic disease. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with intracranial atherosclerotic disease. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serological, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients. © 2017 American Heart Association, Inc.

  4. Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives

    Directory of Open Access Journals (Sweden)

    Graziano Riccioni

    2009-01-01

    Full Text Available Atherosclerosis represents an important chronic inflammatory process associated with several pathophysiological reactions in the vascular wall. The arachidonic acid, released by phospholipase A2, is an important substrate for the production of a group of lipid mediators known as leukotrienes, which induce proinflammatory signaling through the activation of specific BLT and CysLT receptors. The interaction of these substances in the vascular wall determines important morphological alterations like the early lipid retention and the accumulation of foam cells, the development of intimal hyperplasia, and advanced atherosclerotic lesions, and it plays an important role in the rupture of atherosclerotic plaque. Many studies regarding myocardial ischemia and reperfusion show that leukotriene signaling may be involved in the development of ischemic injury. For these, reasons both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested for inducing beneficial effects at different stages of the atherosclerosis process and may represent a new therapeutic target in the treatment of atherosclerotic vessel diseases, in particular in acute coronary syndrome.

  5. Circle of Willis atherosclerosis, Alzheimer's disease and the Dean number.

    Science.gov (United States)

    Ismailov, Rovshan M

    2013-10-26

    The important role of atherosclerosis in pathophysiology of Alzheimer's Disease has become evident. Mechanisms such as hyperlipidemia, inflammation, abdominal obesity and insulin resistance are important yet they may not fully explain the specific involvement of the Circle of Willis in these pathologies. The Circle of Wills is a complex geometrical structure which has several areas with different curvature as well as various branching angles of vessels composing the circle. The hemodynamics in this region should take into account the Dean number which indicates the influence of curvature on the resistance to blood flow. Thus, areas with various curvature and angles may have different hemodynamics and there are certain areas in the Circle of Willis that are more likely to develop atherosclerotic changes. Therefore, this could suggest the novel pathophysiological pathway resulting from the geometric peculiarities of the Circle of Willis. One of the directions of future research is to examine whether specific areas of the Circle of Willis are more likely to develop atherosclerotic changes compared to other ones. Selective areas of the Circle of Willis affected by atherosclerotic changes could indicate the primary role of atherosclerosis promoting Alzheimer's disease although other pathophysiological mechanisms suggesting the opposite direction should be also examined in prospective studies.

  6. 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.

  7. 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

  8. 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.

  9. Genetic predisposition to obesity and risk of subclinical atherosclerosis.

    Science.gov (United States)

    Shi, Juan; Hong, Jie; Qi, Lu; Cui, Bin; Gu, Weiqiong; Zhang, Yifei; Li, Lijuan; Miao, Lin; Wang, Rui; Wang, Weiqing; Ning, Guang

    2014-10-10

    Obesity has been associated with increased common carotid artery (CCA) intima-media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the association between genetic predisposition to obesity and CCA IMT. The study included 428 young Chinese adults with CCA IMT measured using a high-resolution B-mode tomographic ultrasound system. We created a genetic risk score (GRS) by summing the risk alleles of 6 obesity-associated genetic variants confirmed in our previous analyses. The GRS was significantly associated with greater CCA IMT (pobesity status, but remained significant (p=0.009). In addition, we found that blood pressure significantly modified the association between the GRS and CCA IMT (p for interaction=0.001). The associations between the GRS and CCA IMT were stronger in participants with systolic blood pressure (SBP) ≥120 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA IMT, p for trendobesity and development of subclinical atherosclerosis. Elevated blood pressure might amplify the adverse effect of obesity on cardiovascular risk. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. The Different Facets of Dyslipidemia and Hypertension in Atherosclerosis.

    Science.gov (United States)

    Hurtubise, Jessica; McLellan, Krystie; Durr, Kevin; Onasanya, Oluwadara; Nwabuko, Daniel; Ndisang, Joseph Fomusi

    2016-12-01

    Atherosclerosis is the narrowing of arteries due to the accumulation of macrophages overloaded with lipids resulting in foam cell formation, and these events occur preferentially at the branching points of arteries which are particularly susceptible to hyperlipidemic stress-induced inflammation and oxidative stress. The different stages of atherogenesis rely on oxidative stress, endothelial dysfunction, and inflammation, and hypertension or dyslipidemia can independently trigger these stages. Dyslipidemia and hypertension are pathological conditions that damage the endothelium, triggering cell proliferation, vascular remodeling, apoptosis, and increased cellular permeability with increased adhesion molecules that bind monocytes and T lymphocytes to create a vicious cocktail of pathophysiological factors. Correspondingly, the factors are redirected by chemo-attractants and pro-inflammatory cytokines into the intima of the vasculature, where monocytes differentiate into macrophages taking up oxidized LDL uncontrollably to form foam cells and atherosclerotic lesions. Moreover, endothelial damage also causes loss of vasomotor activity, disproportionate vascular contractility, and elevation of blood pressure in dyslipidemic patients, while in hypertensive patients, further elevation of blood pressure occurs, creating a self-perpetuating vicious cycle that aggravates the development and progression of atherosclerotic lesions. This review offers an in-depth analysis of atherosclerosis and the related interplay between dyslipidemia/hypertension and critically appraises the current diagnosis, etiology, and therapeutic options.

  11. CD47 blocking antibodies restore phagocytosis and prevent atherosclerosis

    Science.gov (United States)

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

    2016-01-01

    Summary Atherosclerosis is the disease process underlying heart attack and stroke1. Advanced lesions at risk for rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris2. Why these cells are not cleared remains unknown3. Here we show that atherogenesis is associated with upregulation of CD47, a key ‘don’t eat me’ molecule known to render malignant cells resistant to programmed cell removal (PrCR), or ‘efferocytosis’4–7. 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 PrCR, explaining why this process is compromised in vascular disease. Similar to recent observations in cancer5, 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

  12. Pentraxin 3 and atherosclerosis among type 2 diabetic patients

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    Nabrdalik Katarzyna

    2017-04-01

    Full Text Available Type 2 diabetes is contemporarily a major social and epidemiological problem and among others is a strong risk factor for cardiovascular diseases. Pentraxin 3, a potential early biomarker of atherosclerosis, is an acute-phase reactant produced by the peripheral tissues where the inflammation takes place. In this study we examined a group of patients with type 2 diabetes with and without cardiovascular complications compared to persons with normal glucose tolerance (patients with cardiovascular complications and healthy volunteers. Plasma pentraxin 3 concentration as well as some basic biochemical blood analysis were performed. Moreover, transcranial and carotid Doppler ultrasound examination as well as transthoracic echocardiography were performed. It turned out that there was an association of plasma pentraxin 3 concentration and carotid atherosclerosis found in the control group of patients with cardiovascular complications but with normal glucose tolerance. In the group of patients with type 2 diabetes and cardiovascular complications we have found an association of plasma pentraxin 3 concentration with diastolic left ventricular dysfunction. Additionally, in the group of patients with type 2 diabetes without cardiovascular disease plasma pentraxin 3 concentration was associated with elevated urinary albumin creatinine ratio. Further studies, on a larger group of patients, are required to confirm these observations.

  13. Obesity Is Associated With Progression of Atherosclerosis During Statin Treatment.

    Science.gov (United States)

    Sandfort, Veit; Lai, Shenghan; Ahlman, Mark A; Mallek, Marissa; Liu, Songtao; Sibley, Christopher T; Turkbey, Evrim B; Lima, João A C; Bluemke, David A

    2016-07-13

    This study aimed to determine the relationship of statin therapy and cardiovascular risk factors to changes in atherosclerosis in the carotid artery. Carotid magnetic resonance imaging was used to evaluate 106 hyperlipidemic participants at baseline and after 12 months of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) treatment. Multivariable logistic regression was used to determine factors associated with progression (change in carotid wall volume >0) or regression (change ≤0) of carotid atherosclerosis. Computed tomography coronary calcium scores were obtained at baseline for all participants. The median age was 65 years (interquartile range 60-69 years), and 63% of the participants were male. Body mass index >30, elevated C-reactive protein, and hypertension were associated with increased carotid wall volume (obesity: odds ratio for progression 4.6, 95% CI 1.8-12.4, Pobesity remained associated with progression (Pobese participants was +4.8% versus -4.2% in nonobese participants (Pobese participants. In a population with hyperlipidemia, obese patients showed atheroma progression despite optimized statin therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01212900. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. SASH1, a new potential link between smoking and atherosclerosis.

    Science.gov (United States)

    Weidmann, Henri; Touat-Hamici, Zahia; Durand, Herve; Mueller, Christian; Chardonnet, Solenne; Pionneau, Cedric; Charlotte, Frédéric; Janssen, Klaus-Peter; Verdugo, Ricardo; Cambien, Francois; Blankenberg, Stefan; Tiret, Laurence; Zeller, Tanja; Ninio, Ewa

    2015-10-01

    We have previously reported that SASH1 expression is increased in circulating human monocytes from smokers and was positively correlated with the number of carotid atherosclerotic plaques. The aim of this study was to further validate the link between smoking, SASH1 and atherosclerosis within the vascular wall and to assess the impact of SASH1 expression on endothelial cell functions. Human carotids with atherosclerotic plaques were obtained from 58 patients (45 of them with known smoking status: smoker, non-smoker, ex-smokers), and were processed for gene expression analyses and immunostaining. To investigate its function, SASH1 was silenced in human aortic endothelial cells (HAECs) using two different siRNA and subcellular localization of SASH1 was determined by immunostaining and subcellular fractionation. Subsequently the transcriptomic analyses and functional experiments (wound healing, WST-1 proliferation or Matrigel assays) were performed to characterize SASH1 function. SASH1 was expressed in human vascular cells (HAECs, smooth muscle cells) and in monocytes/macrophages. Its tissue expression was significantly higher in the atherosclerotic carotids of smokers compared to non-smokers (p atherosclerosis through SASH1 expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. MicroRNAs and lipoproteins: a connection beyond atherosclerosis?

    Science.gov (United States)

    Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernández-Hernando, Carlos

    2014-01-01

    MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

  17. Ambient air pollution and the progression of atherosclerosis in adults.

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    Nino Künzli

    Full Text Available BACKGROUND: Cross-sectional studies suggest an association between exposure to ambient air pollution and atherosclerosis. We investigated the association between outdoor air quality and progression of subclinical atherosclerosis (common carotid artery intima-media thickness, CIMT. METHODOLOGY/PRINCIPAL FINDINGS: We examined data from five double-blind randomized trials that assessed effects of various treatments on the change in CIMT. The trials were conducted in the Los Angeles area. Spatial models and land-use data were used to estimate the home outdoor mean concentration of particulate matter up to 2.5 micrometer in diameter (PM2.5, and to classify residence by proximity to traffic-related pollution (within 100 m of highways. PM2.5 and traffic proximity were positively associated with CIMT progression. Adjusted coefficients were larger than crude associations, not sensitive to modelling specifications, and statistically significant for highway proximity while of borderline significance for PM2.5 (P = 0.08. Annual CIMT progression among those living within 100 m of a highway was accelerated (5.5 micrometers/yr [95%CI: 0.13-10.79; p = 0.04] or more than twice the population mean progression. For PM2.5, coefficients were positive as well, reaching statistical significance in the socially disadvantaged; in subjects reporting lipid lowering treatment at baseline; among participants receiving on-trial treatments; and among the pool of four out of the five trials. CONCLUSION: Consistent with cross-sectional findings and animal studies, this is the first study to report an association between exposure to air pollution and the progression of atherosclerosis--indicated with CIMT change--in humans. Ostensibly, our results suggest that air pollution may contribute to the acceleration of cardiovascular disease development--the main causes of morbidity and mortality in many countries. However, the heterogeneity of the volunteering populations across the

  18. 70. Epicardial fat quality effect on subclinical atherosclerosis

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    R. Abazid

    2016-07-01

    Full Text Available Epicardial fat quality measured as Hounsfield Unit (HU by computed tomography has significant impact on atherosclerosis. Excessive epicardial adipose tissue (EAT is considered a risk factor for coronary artery disease (CAD. There are limited data, however, about the quality of epicardial fat as a CAD risk factor. We investigated the relation between EAT volume and quality and subclinical CAD defined by positive coronary artery calcification (CAC using computed tomography (CT. We reviewed 609 CT scans to assess the EAT volume, which was measured by manually tracing the parietal pericardial sac on axial images. Fat density was recorded in mean Hounsfield units (HU. Coronary calcium scores were measured using the Agatston method. The patients’ mean age was 50 ± 11 years, and 398 (65.4% were men. The mean EAT volume was 65 ± 27 cm3, and it had a density of 87.0 ± 3.4 HU. Calcium was present in 135 (22% of the patients: 97 (16% of the total were men and 38 (6% were women. There was no difference between the sexes in regard to EAT volume (66 ± 27 vs. 63 ± 26, p = 0.34 or density (87.4 ± 3.2 vs. 87.0 ± 3.6, p = 0.28. Obese patients (body mass index ⩾30 kg/m2 had significantly higher EAT volumes than nonobese patients (73 ± 30 vs. 61 ± 29, p = 0.011, but no difference was seen in CAC (33 ± 97 vs. 27 ± 103, p = 0.34 or fat density (87.7 ± 4.0 vs. 88.0 ± 2.7, p = 0.48. Univariate regression analyses showed that higher fat attenuation (HU was associated with a lower coronary atherosclerosis hazard ratio (HR (0.871, 95% confidence interval [CI] 0.790–0.948, p < 0.0001, and an increased EAT volume was associated with more CAC (HR 1.16, 95% CI 1.078–1.245, p = 0.0001. The quality of EAT, measured as HU on CT, is a strong predictor of subclinical CAD as defined by coronary artery calcifications, with a higher HU associated with a lower incidence of atherosclerosis.

  19. 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-ty...... 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.......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 NX mice fed the Western-type diet (n = 7), the total plasma cholesterol concentration was similar to that in sham mice (n = 11), but on gel filtration the LDL/HDL cholesterol ratio was increased. HDL from NX mice contained more serum amyloid A and triglycerides and less cholesterol than HDL from sham...

  20. Cardiovascular disturbances and atherosclerosis risk Гасtore in systemic lupus erythematosus

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    T V Popkova

    2004-01-01

    Full Text Available Objective. To assess frequency and significance of atherosclerosis and connected with it cardiovascular disturbances (CVD risk factors in pts wilh systemic lupus erythematosus (SLE. Material and methods. 99 pts (mean age 35,9± 10,8 years, mean disease duration 106± 115,5 months were examined. Classical risk factors were analyzed. Coronary complications risk was assessed with "Scheme of individual total (general coronary heart disease (CHD clinical signs risk determination”. Duplex scanning of common carotid arteries was performed. C-reactive protein (CRP was evaluated by high-sensitivity immune-enzyme assay with Bender MedSystems commercial kits. Results. 92% of SLE pts had at least one classical atherosclerosis risk factor, most often - dislipidemia (DLP or hypertension (HT. Subclinical atherosclerosis signs characterized by increase of intima-media complex thickness and DLP were more frequent in pts with HT than without HT (p=0,00l and p=0,008 respectively. Total CHD clinical signs risk in group with atherosclerosis features was higher than in group of pts without atherosclerosis (p=0,0001.A positive correlation between total risk of coronary complications and CRP concentration (r=0,27, p=0,02. Conclusion. Classical and some "ersatz" risk factors are of considerable significance in atherosclerosis and connected with it CVD progression. Multiple-factor analysis of different indices and evaluation of their role in the CVD development in SLE pts are essential for examination of mechanisms of early atherosclerosis development.

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

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    Mehrnoosh Sedighi

    2017-01-01

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

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

    Science.gov (United States)

    Sedighi, Mehrnoosh; Bahmani, Mahmoud; Asgary, Sedigheh; Beyranvand, Fatemeh; Rafieian-Kopaei, Mahmoud

    2017-01-01

    Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications. PMID:28461816

  3. Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study.

    Science.gov (United States)

    Fernández-Alvira, Juan M; Fuster, Valentin; Dorado, Beatriz; Soberón, Nora; Flores, Ignacio; Gallardo, Mercedes; Pocock, Stuart; Blasco, María A; Andrés, Vicente

    2016-05-31

    Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown. The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTLSubclinical Atherosclerosis) study. Subclinical atherosclerosis was evaluated by coronary artery calcium scan and 2-dimensional/3-dimensional ultrasound in different aortic territories. Statistical significance of differences among multiple covariates was assessed with linear regression models. Independent associations of telomere parameters with plaque presence were evaluated using general linear models. In men and women, age was inversely associated with LTL (Pearson's r = -0.127, p subclinical atherosclerosis. Longitudinal follow-up of PESA participants will assess long-term associations between telomere length and progression of subclinical atherosclerosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Carotid versus coronary atherosclerosis burdens in acute compared with chronic symptomatic coronary artery disease.

    Science.gov (United States)

    LeBlanc, Stéphanie; Bibeau, Karine; Bertrand, Olivier F; Lévesque, Valérie; Deschênes St-Pierre, Béatrice; Pibarot, Philippe; Després, Jean-Pierre; Larose, Eric

    2017-08-01

    Prediction of coronary events remains elusive. Carotid atherosclerosis may be a surrogate for coronary risk, as carotid and coronary diseases occur simultaneously - albeit at times with a weak association - depending on clinical presentation. We investigated carotid and coronary atherosclerosis in men with new-onset unstable coronary artery disease (CAD) presenting with acute ST-segment elevation myocardial infarction (STEMI) vs. long-standing severe chronic stable angina (CSA). Bilateral carotid artery and 3-vessel coronary artery atherosclerosis burdens were measured within 1 month, respectively, by 3D-volumetric carotid magnetic resonance imaging and coronary angiography-derived modified CASS-50 score. Men with STEMI (n = 50) and long-standing CSA (n = 50), matched for age, were enrolled (58.6 ± 8.8 years). All of them had carotid atherosclerosis. Atherosclerosis burden was greater in the carotid arteries of STEMI vs. CSA (wall volume: 196.2 ± 44.4 vs. 169.2 ± 38.0 mm3/4 mm, p = 0.002), but greater in the coronary arteries of CSA vs. STEMI (modified CASS-50 score: 3 vs. 1, p < 0.0001). Normalized wall index (NWI) of internal carotid was associated with modified CASS-50 score in STEMI (ρ = 0.40, p = 0.022) and in CSA (ρ = -0.39, p = 0.031). Carotid atherosclerosis was observed in all CAD patients, and atherosclerosis burden in carotid and in coronary arteries varied according to clinical presentation.

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

    Science.gov (United States)

    Bjørklund, Martin Maeng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup; Dagnaes-Hansen, Frederik; Christoffersen, Christina; Mikkelsen, Jacob Giehm; Bentzon, Jacob Fog

    2014-05-23

    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. To develop a method for induction of atherosclerosis without germline genetic engineering. Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions to the fibroatheromatous stage. To demonstrate the applicability of this method for rapid analysis of the atherosclerosis susceptibility of a mouse strain and for providing temporal control over disease induction, we demonstrated the accelerated atherosclerosis of mature diabetic Akita mice. Furthermore, the versatility of this approach for creating atherosclerosis models also in nonmurine species was demonstrated by inducing hypercholesterolemia and early atherosclerosis in Golden Syrian hamsters. Single injections of proprotein convertase subtilisin/kexin type 9-encoding recombinant adeno-associated viral vectors are a rapid and versatile method to induce atherosclerosis in animals. This method should prove useful for experiments that are high-throughput or involve genetic techniques, strains, or species that do not combine well with current genetically engineered models. © 2014 American Heart Association, Inc.

  6. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.

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    Johan L M Björkegren

    2014-02-01

    Full Text Available Plasma cholesterol lowering (PCL slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80% and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-Apob (100/100 Mttp (flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions.

  7. [Optimization of organizational approaches to management of patients with atherosclerosis].

    Science.gov (United States)

    Barbarash, L S; Barbarash, O L; Artamonova, G V; Sumin, A N

    2014-01-01

    Despite undoubted achievements of modern cardiology in prevention and treatment of atherosclerosis, cardiologists, neurologists, and vascular surgeons are still facing severe stenotic atherosclerotic lesions in different vascular regions, both symptomatic and asymptomatic. As a rule hemodynamically significant stenoses of different locations are found after development of acute vascular events. In this regard, active detection of arterial stenoses localized in different areas just at primary contact of patients presenting with symptoms of ischemia of various locations with care providers appears to be crucial. Further monitoring of these stenoses is also important. The article is dedicated to innovative organizational approaches to provision of healthcare to patients suffering from circulatory system diseases that have contributed to improvement of demographic situation in Kuzbass.

  8. HDL functionality and crystal-based sterile inflammation in atherosclerosis.

    Science.gov (United States)

    Eren, Esin; Ellidag, Hamit Yasar; Aydin, Ozgur; Yilmaz, Necat

    2015-01-15

    Change is inevitable. In early evolution, due to the limited availability of resources, the sole purpose of living organisms was to survive long enough to transmit their genes to the next generation. During their short lifetime, organisms used pathogen-associated and damage-associated molecular pattern pathways as an inflammatory response against pathogens (exogenous factors) and tissue damage (endogenous factors), respectively. Despite advances in human lifespan, it appears that an increasing number of diseases such as atherosclerosis are associated with inflammation. Excessive glucose, lipid and protein intake leads to the formation of endogenous crystals, i.e., cholesterol, which can induce a sterile inflammatory immune response that manifests as a vicious cycle. In this review, we evaluate the possible relationship between crystal-based sterile inflammatory response and HDL functionality. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    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

  10. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

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

    2010-01-01

    Uremic patients have increased plasma lipoprotein(a) [Lp(a)] levels and elevated risk of cardiovascular disease. Lp(a) is a subfraction of LDL, where apolipoprotein(a) [apo(a)] is disulfide bound to apolipoprotein B-100 (apoB). Lp(a) binds oxidized phospholipids (OxPL), and uremia increases...... = 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...

  11. Linoleic acid amides: effect on cholesteremia and atherosclerosis.

    Science.gov (United States)

    Kritchevsky, D; Tepper, S A; Story, J A

    1977-01-01

    Several of a series of linoleic acid amides have been reported to inhibit cholesterol-induced atherosclerosis in rabbits. The three amides which have been studied to the greatest extent are (in order of increasing activity) N-cyclohexyl linoleamide (AC23), N(alpha methylbenzyl) linoleamide (AC223), and N[aplha-phenyl-beta-(p-tolyl)ethyl] linoeamide (AC 485). We have found AC223 to inhibit cholesterol absorption in rats and to slightly inhibit exogenous but not endogenous cholesteremia in rabbits. In a fiber-free diet, AC223 reduces serum cholesterol and liver triglyceride levels. Rats were also fed a basal semipurified diet with and without AC223. Fecal excretion of labeled exogenous (as [ (14)C] cholesterol) or endogenous (as [14 C] mevalonolactone) steroid was 44 and 43% higher in drug treated groups. The mechanism of hypocholesteremic action of the linoleamides appears to involve inhibition of cholesterol absorption.

  12. PET/MR imaging of atherosclerosis: initial experience and outlook.

    Science.gov (United States)

    Rischpler, Christoph; Nekolla, Stephan G; Beer, Ambros J

    2013-01-01

    Hybrid scanners such as PET/CT have in the past emerged as a valuable modality in clinical routine as well as an important research tool. Recently, the newly developed fully integrated PET/MR scanners were introduced to the market, raising high expectations especially due to the excellent soft tissue contrast and functional imaging capabilities of MRI. In this issue of the American Journal of Nuclear Medicine and Molecular Imaging, initial experiences using a hybrid PET/MR scanner for carotid artery imaging in a group of patients with increased risk for atherosclerosis are described. This represents a proof-of-principle study, which could stimulate future applications of this powerful modality in atherosclerotic plaque imaging.

  13. 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.

  14. The LDL/HDL ratio and atherosclerosis in ankylosing spondylitis.

    Science.gov (United States)

    Kucuk, A; Uğur Uslu, A; Icli, A; Cure, E; Arslan, S; Turkmen, K; Toker, A; Kayrak, M

    2017-02-01

    In ankylosing spondylitis (AS) patients, cardiac and vascular involvement may manifest as atherosclerosis and coronary artery disease. Systemic inflammation, oxidative stress, increased low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol constitute a significant risk for atherosclerosis. This study investigated the relationship between carotid intima-media thickness (CIMT), LDL/HDL ratio, total oxidant status (TOS; an indicator of oxidative stress) and ischemic modified albumin (IMA; an ischemic marker in AS patients). Sixty AS patients were diagnosed using the Modified New York Criteria; 54 age- and gender-matched participants were included as controls. CIMT, LDL/HDL ratio, TOS and IMA were measured using the most appropriate methods. IMA was higher in AS patients compared to controls (p < 0.0001). TOS was also increased in AS patients (p = 0.005); as was CIMT (p < 0.0001). The LDL/HDL ratio was also greater in AS patients compared to controls (p = 0.047). A positive correlation was found between CIMT and LDL/HDL ratio among AS patients. Elevated CIMT, IMA and TOS levels suggest an increased risk of atherosclerotic heart disease in AS patients. The LDL/HDL ratio was higher in AS patients compared to controls, and there was a correlation between LDL/HDL ratio and CIMT, albeit statistically weak. Therefore, the LDL/HDL ratio is not a reliable marker to predict atherosclerotic heart disease in AS patients.

  15. Dietary micronutrient intake and atherosclerosis in systemic lupus erythematosus.

    Science.gov (United States)

    Lourdudoss, C; Elkan, A-C; Hafström, I; Jogestrand, T; Gustafsson, T; van Vollenhoven, R; Frostegård, J

    2016-12-01

    The aim of this study was to investigate the role of dietary micronutrient intake in systemic lupus erythematosus (SLE). This study included 111 SLE patients and 118 age and gender-matched controls. Data on diet (food frequency questionnaires) were linked with data on Systemic Lupus Activity Measure, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and carotid atherosclerotic/echolucent plaque (B-mode ultrasound). Dietary micronutrient intake were compared between SLE patients and controls and in relation to lupus activity and atherosclerosis in SLE. Associations between micronutrient intake and plaque were analyzed through logistic regression, adjusted for potential confounders. Micronutrient intake did not differ between patients and controls, and between lower and higher lupus activity, apart from the fact that phosphorus was associated with SLEDAI > 6. In SLE patients, some micronutrients were associated with atherosclerotic plaque, left side. Lower intake of riboflavin and phosphorus was associated with atherosclerotic plaque, left side (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.12-8.40 and OR 4.36, 95% CI 1.53-12.39, respectively). Higher intake of selenium and thiamin was inversely associated with atherosclerotic plaque, left side (OR 0.28, 95% CI 0.09-0.89 and OR 0.26, 95% CI 0.08-0.80, respectively). In addition, higher intake of thiamin was inversely associated with echolucent plaque, left side (OR 0.22, 95% CI 0.06-0.84). Lower intake of folate was inversely associated with bilateral echolucent plaque (OR 0.36, 95% CI 0.13-0.99). SLE patients did not have different dietary micronutrient intake compared to controls. Phosphorus was associated with lupus activity. Riboflavin, phosphorus, selenium and thiamin were inversely associated with atherosclerotic plaque, left side in SLE patients, but not in controls. Dietary micronutrients may play a role in atherosclerosis in SLE. © The Author(s) 2016.

  16. Novel aspects of postprandial lipemia in relation to atherosclerosis.

    Science.gov (United States)

    Alipour, A; Elte, J W F; van Zaanen, H C T; Rietveld, A P; Castro Cabezas, M

    2008-09-01

    Postprandial hyperlipidemia is considered to be a substantial risk factor for atherosclerosis. Interestingly, this concept has never been supported by randomized clinical trials. The difficulty lies in the fact that most interventions aimed to reduce postprandial lipemia, will also affect LDL-C levels. The atherogenic mechanisms of postprandial lipids and lipoproteins can be divided into direct lipoprotein-mediated and indirect effects; the latter, in part, by inducing an inflammatory state. Elevations in postprandial triglycerides (TG) have been related to the increased expression of postprandial leukocyte activation markers, up-regulation of pro-inflammatory genes in endothelial cells and involvement of the complement system. This set of events is part of the postprandial inflammatory response, which is one of the recently identified potential pro-atherogenic mechanisms of postprandial lipemia. Especially, complement component 3 levels show a close correlation with postprandial lipemia and are also important determinants of the metabolic syndrome. In clinical practice, fasting TG are frequently used as reflections of postprandial lipemia due to the close correlation between the two. The use of serial capillary measurements in an out-of-hospital situation is an alternative for oral fat loading tests. Daylong TG profiles reflect postprandial lipemia and are increased in conditions like the metabolic syndrome, type 2 diabetes and atherosclerosis. Studies are needed to elucidate the role of postprandial inflammation in atherogenesis and to find new methods in order to reduce selectively the postprandial inflammatory response. Future studies are needed to find new methods in order to reduce selectively the postprandial inflammatory response.

  17. Traumatic brain injury, coronary atherosclerosis and cardiovascular mortality.

    Science.gov (United States)

    Ahmadi, Naser; Hajsadeghi, Fereshteh; Yehuda, Rachel; Anderson, Nils; Garfield, David; Ludmer, Charles; Vaidya, Nutan

    2015-01-01

    Traumatic-brain-injury (TBI) is a devastating-condition resulting in cerebral edema and ischemia. This study investigates the association of mild-TBI (mTBI) to sub-clinical atherosclerosis and cardiovascular (CV) mortality. Five hundred and forty-three veterans without known coronary artery disease or diagnosed mental disorder, who underwent coronary artery calcium (CAC) scanning for clinical indications, were followed for a median of 4-years. Veterans' medical diagnoses and neuropsychiatric health status (mTBI vs non-mTBI) were evaluated using VA electronic medical records. CAC was defined as 0, 1-100, 101-400 and 400+. CAC was higher in mTBI, compared to without-mTBI (p mortality rate was 25% in mTBI and 10.5% in without-mTBI (p = 0.0001). Multivariable survival regression analyses revealed a significant-association between mTBI and CAC, with increased-risk of CV mortality (p mortality was 5.25 in mTBI & CAC > 0, compared to without-mTBI & CAC = 0 (p mortality was 2.25 for mTBI & CAC = 1-100, 4.93 for mTBI & CAC = 101-400 and 7.06 for mTBI & CAC ≥ 400, compared to matched CAC-categories without-mTBI (p mortality was 0.64 for mTBI, 0.69 for mTBI & PTSD, 0.85 for mTBI & CAC > 0 and 0.92 for the combination. The prognostication of mTBI to predict CV mortality is superior to the Framingham risk score. Also the combination of mTBI & PTSD provided incremental prognostic values to predict CV mortality (p atherosclerosis and independently predicts CV mortality.

  18. Red cell distribution width and mortality in carotid atherosclerosis.

    Science.gov (United States)

    Wonnerth, Anna; Krychtiuk, Konstantin A; Mayer, Florian J; Minar, Erich; Wojta, Johann; Schillinger, Martin; Koppensteiner, Renate; Hoke, Matthias

    2016-02-01

    Red cell distribution width (RDW) is associated with morbidity and mortality in chronic cardiac disease. The aim of the present study was to investigate the role of RDW as a predictor of adverse outcome in patients with carotid atherosclerosis. We prospectively studied 1065 of 1286 consecutive patients with neurological asymptomatic carotid artery stenosis as assessed by duplex Doppler sonography. The study end points were all-cause mortality and cardiovascular mortality respectively. During a median follow-up time of 6·2 years (interquartile range 5·9-6·6), corresponding to 5551 overall person-years, 275 patients (25·8%) died. Of them, 182 patients (66·2%) died due to cardiovascular causes. RDW was significantly associated with adverse outcome. In a continuous multivariate Cox regression analysis, the adjusted hazard ratio for each per cent increase in RDW was 1·39 (95% CI 1·27-1·53; P < 0·001) for all-cause and 1·43 (95% CI 1·28-1·60; P < 0·001) for cardiovascular mortality respectively. Kaplan-Meier estimates showed a gradual relationship between increasing quartiles of RDW and death (log rank P < 0·001). Adjusted hazard ratios for all-cause death ranged from 0·89 to 1·94 for the highest vs. the lowest quartile (P < 0·001 for trend) and for cardiovascular death from 1·08 to 2·34 for the highest vs. the lowest quartile (P < 0·001 for trend) respectively. Red cell distribution width was significantly and independently associated with all-cause and cardiovascular death in patients with asymptomatic carotid atherosclerosis. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  19. New aspects on the metabolic role of intestinal microbiota in the development of atherosclerosis.

    Science.gov (United States)

    Drosos, Ioannis; Tavridou, Anna; Kolios, George

    2015-04-01

    Gut microbiota remains a very interesting, yet largely unexplored ecosystem inside the human organism. The importance of this ecosystem for the physiology and the pathophysiology of the organism is being slowly unraveled. Recent studies reveal a connection between intestinal microbiota and atherosclerosis development. It seems that alterations in the function and composition of this bacterial population lead through complex mechanisms to a high risk for atherosclerosis. Although these mechanisms remain largely unknown, published studies show that microbiota can lead to atherosclerosis either by augmenting known risk factors or via other, more "direct" mechanisms. This review article summarizes the available literature regarding this matter. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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

  1. Characteristics of erythrocyte-derived microvesicles and its relation with atherosclerosis.

    Science.gov (United States)

    Li, Kai-Yin; Zheng, Lei; Wang, Qian; Hu, Yan-Wei

    2016-12-01

    Microvesicles are formed under many circumstances, especially in atheromatous plaques. Erythrocyte-derived microvesicles (ErMVs) have been proved to promote atherosclerosis by promoting hypercoagulation, mediating inflammation and inducing cell adhesion. Several clinical studies have reported potential roles of ErMVs in cardiovascular disease diagnosis, but the current understanding of ErMVs remains insufficient. In this paper, we will review current research on the formation and degradation of ErMVs and the possible effects of ErMVs in atherosclerosis, discuss potential clinical applications in cardiovascular disease, and hope to raise awareness of the relation with atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. T-helper type 1 bias in healthy people is associated with cytomegalovirus serology and atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Tracy, Russell P; Doyle, Margaret F; Olson, Nels C; Huber, Sally A; Jenny, Nancy S; Sallam, Reem; Psaty, Bruce M; Kronmal, Richard A

    2013-05-20

    Although T-helper type 1 (Th1) cells are considered important in atherosclerosis, the relationships between Th1 and Th2 cells and atherosclerosis have not been examined in population-based studies. We measured Th cells as a percentage of lymphocytes by flow cytometry using CD4 staining (%CD4) in 917 participants of the Multi-Ethnic Study of Atherosclerosis. We also measured interferon gamma-positive and interleukin-4-positive CD4(+) cells, representing Th1 and Th2 subpopulations (%Th1 and %Th2), respectively. We found that %CD4 was 1.5% lower per 10 years of age (Pmedia thickness (β=0.02 and -0.02, respectively; both Pbias is associated with subclinical atherosclerosis in a multiethnic population. The main Th1 correlate was CMV infectious burden. These findings are consistent with a role of Th1 cells in atherosclerosis and suggest the importance of prospective studies of T-helper cell biasing in CVD.

  3. Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

    2015-04-01

    The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    Camargo, Alejandra B; Manucha, Walter

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

  5. Increasing HDL-cholesterol and prevention of atherosclerosis: A critical perspective.

    Science.gov (United States)

    Parhofer, Klaus G

    2015-05-01

    The relationship between atherosclerosis and HDL is more complex than between LDL and atherosclerosis. Low HDL-cholesterol is associated with atherosclerotic disease not in a causal way but because low HDL-cholesterol reflects an increased concentration of triglyceride-rich lipoproteins. At the same time the functionality of the HDL system plays an important role in atherosclerosis prevention (for example by mediating reverse cholesterol transport). However, these two observations are not directly linked to each other. Therefore therapeutic strategies must either aim at decreasing the concentration of triglyceride-rich lipoproteins (and thereby increase HDL-cholesterol concentration) or at improving HDL function (which may or may not affect HDL-cholesterol concentration). Simply increasing HDL-cholesterol concentration without improving function or decreasing triglyceride-rich lipoproteins will not be beneficial with respect to atherosclerosis prevention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Role of endoplasmic reticulum stress signalling in diabetic endothelial dysfunction and atherosclerosis.

    Science.gov (United States)

    Dong, Yunzhou; Fernandes, Conrad; Liu, Yanjun; Wu, Yong; Wu, Hao; Brophy, Megan L; Deng, Lin; Song, Kai; Wen, Aiyun; Wong, Scott; Yan, Daoguang; Towner, Rheal; Chen, Hong

    2017-01-01

    It is well established that diabetes mellitus accelerates atherosclerotic vascular disease. Endothelial injury has been proposed to be the initial event in the pathogenesis of atherosclerosis. Endothelium not only acts as a semi-selective barrier but also serves physiological and metabolic functions. Diabetes or high glucose in circulation triggers a series of intracellular responses and organ damage such as endothelial dysfunction and apoptosis. One such response is high glucose-induced chronic endoplasmic reticulum stress in the endothelium. The unfolded protein response is an acute reaction that enables cells to overcome endoplasmic reticulum stress. However, when chronically persistent, endoplasmic reticulum stress response could ultimately lead to endothelial dysfunction and atherosclerosis. Herein, we discuss the scientific advances in understanding endoplasmic reticulum stress-induced endothelial dysfunction, the pathogenesis of diabetes-accelerated atherosclerosis and endoplasmic reticulum stress as a potential target in therapies for diabetic atherosclerosis. © The Author(s) 2016.

  7. 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...

  8. Kidney Measures with Diabetes and Hypertension on Cardiovascular Disease : The Atherosclerosis Risk in Communities Study

    NARCIS (Netherlands)

    Alexander, Nadine; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana; Mahmoodi, Bakhtawar K.; Astor, Brad C.; Coresh, Josef

    2015-01-01

    Background: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered. Methods: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination

  9. Recent advances and clinical insights into the use of proteomics in the study of atherosclerosis.

    Science.gov (United States)

    Mourino-Alvarez, Laura; Baldan-Martin, Montserrat; Rincon, Raul; Martin-Rojas, Tatiana; Corbacho-Alonso, Nerea; Sastre-Oliva, Tamara; Barderas, Maria G

    2017-08-01

    The application of new proteomics methods may help to identify new diagnostic/predictive molecular markers in an attempt to improve the clinical management of atherosclerosis. Areas covered: Technological advances in proteomics have enhanced its sensitivity and multiplexing capacity, as well as the possibility of studying protein interactions and tissue structure. These advances will help us better understand the molecular mechanisms at play in atherosclerosis as a biological system. Moreover, this should help identify new predictive/diagnostic biomarkers and therapeutic targets that may facilitate effective risk stratification and early diagnosis, with the ensuing rapid implementation of treatment. This review provides a comprehensive overview of the novel methods in proteomics, including state-of-the-art techniques, novel biological samples and applications for the study of atherosclerosis. Expert commentary: Collaboration between clinicians and researchers is crucial to further validate and introduce new molecular markers to manage atherosclerosis that are identified using the most up to date proteomic approaches.

  10. 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 ...

  11. Atherosclerosis in chronic hepatitis C virus patients with and without liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Ashraf Abd El-Khalik Barakat

    2017-06-01

    The echocardiographic assessment of EpFT and the carotid Doppler assessment of CIMT may provide appropriate and simple screening markers for subclinical atherosclerosis and cardiovascular risk in chronic HCV patients with and without cirrhosis.

  12. 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

  13. 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.

  14. Evaluation of subclinical atherosclerosis in migraine patients by ultrasound radiofrequency data technology: preliminary results.

    Science.gov (United States)

    Güneş Tatar, İdil; Ergun, Onur; Çeltikçi, Pınar; Kurt, Aydın; Yavaşoğlu, Neşe; Birgi, Erdem; Tatar, Tolga; Hekimoğlu, Baki

    2016-07-01

    Migraine is a headache disorder affecting approximately 12% of the population, predominantly female individuals. Migraine has been associated with vascular events such as stroke and cardiovascular disease. The close connection between these vascular disorders and atherosclerosis is well known. Carotid artery intima-media thickness (CAIMT) is a marker for detection of subclinical atherosclerosis. The present study is an analysis of the presence of subclinical atherosclerosis in migraine patients. CAIMT was evaluated in 25 female migraine patients and 27 female controls using innovative ultrasound (US) radiofrequency (RF) data technology. Mann-Whitney U test was used to compare measurements in patient and control groups. There was a statistically significant difference between mean CAIMT of migraine patients and control group (patherosclerosis compared to healthy individuals. CAIMT measurement with sonography can be utilized in follow-up to detect subclinical atherosclerosis.

  15. Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis

    NARCIS (Netherlands)

    McLeod, Olga; Silveira, Angela; Fredrikson, Gunilla N.; Gertow, Karl; Baldassarre, Damiano; Veglia, Fabrizio; Sennblad, Bengt; Strawbridge, Rona J.; Larsson, Malin; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Ohrvik, John; Nilsson, Jan; Hamsten, Anders

    Objective: Experimental studies have suggested that autoimmunity is involved in atherosclerosis and provided evidence that both protective and pro-atherogenic immune responses exist. This concept has received support from small clinical studies implicating autoantibodies directed against

  16. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes. Animal studies suggest that GLP-1 also dampens inflammation and atherosclerosis. Our.......c. once daily) or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-), CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation....... Furthermore, markers of fibrosis (i.e. Col1a1 and Col3a1) were upregulated, and histological examinations showed increased glomerular diameter in NX mice. Importantly, liraglutide treatment attenuated atherosclerosis (~40%, p inflammation in NX mice. There was no effect...

  18. 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

  19. Hemodynamic Markers and Subclinical Atherosclerosis in Postmenopausal Women With Primary Hyperparathyroidism

    National Research Council Canada - National Science Library

    Stamatelopoulos, Kimon; Athanasouli, Fani; Pappa, Theodora; Labrinoudaki, Irene; Papamichael, Christos; Polymeris, Antonis; Georgiopoulos, Georgios; Vemmou, Anastasia; Sarika, Leda; Terpos, Evangelos; Alevizaki, Maria

    2014-01-01

    ...: The objective of the study was to assess whether pHPT is associated with hemodynamic markers and subclinical atherosclerosis in postmenopausal women under a cross-sectional case-control design. Methods...

  20. A review of macrolide treatment of atherosclerosis and abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Stovring, Jette; Andersen, Paul Lehm

    2003-01-01

    Seroepidemiological studies have shown an association between Chlamydia pneumoniae and atherosclerosis, the risk of acute myocardial infarction and abdominal aortic aneurysms (AAA). Several studies have detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in AAA, ...

  1. Effects of catechins and caffeine on the development of atherosclerosis in mice.

    Science.gov (United States)

    Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

    2017-10-01

    Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

  2. Disruption of mammalian target of rapamycin complex 1 in macrophages decreases chemokine gene expression and atherosclerosis

    NARCIS (Netherlands)

    Ai, Ding; Jiang, Hongfeng; Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Ganda, Anjali; Abramowicz, Sandra; Welch, Carrie; Almazan, Felicidad; Zhu, Yi; Miller, Yury I.; Tall, Alan R.

    2014-01-01

    The mammalian target of rapamycin complex 1 inhibitor, rapamycin, has been shown to decrease atherosclerosis, even while increasing plasma low-density lipoprotein levels. This suggests an antiatherogenic effect possibly mediated by the modulation of inflammatory responses in atherosclerotic plaques.

  3. Association between a social-business eating pattern and early asymptomatic atherosclerosis

    Science.gov (United States)

    BACKGROUND: The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. OBJECTIVES: This study sought to quanti...

  4. 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...

  5. Comparison of Antidiabetic Medications during the Treatment of Atherosclerosis in T2DM Patients

    OpenAIRE

    Xiaojie Liu; Tao Mei; Wei Chen; Shandong Ye

    2017-01-01

    Type 2 diabetes is often associated with arterial atherosclerosis in large blood vessels. We set out to elucidate whether commonly used antidiabetic drugs metformin, sitagliptin, and pioglitazone will reduce atherosclerosis in T2DM patients. We enrolled 176 individuals with type 2 diabetes, which were divided into four treatment groups according to different oral drugs: metformin alone, sitagliptin alone, pioglitazone alone, or combination of metformin and sitagliptin. We assessed changes in ...

  6. Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs.

    Science.gov (United States)

    Gibson, Frank C; Genco, Caroline A

    2007-01-01

    Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Furthermore hyperlipidemic mice deficient in TLR2, TLR4, and MyD88 signaling exhibit diminished inflammatory responses and decreased atherosclerosis. Accumulating evidence has implicated specific infectious agents including the periodontal disease pathogen Porphyromonas gingivalis in the progression of atherosclerosis. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen P. gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. We have established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local and distant chronic inflammation induced by this pathogen. We have demonstrated that P. gingivalis requires TLR2 to induce oral inflammatory bone lose in mice. Furthermore, we have demonstrated that P. gingivalis infection accelerates atherosclerosis in hyperlipidemic mice with an associated increase in expression of TLR2 and TLR4 in atherosclerotic lesions. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. Improved understanding of the mechanisms driving infection, and chronic inflammation during atherosclerosis may ultimately provide new targets for therapy.

  7. Serum gamma-glutamyltransferase is not associated with subclinical atherosclerosis in patients with type 2 diabetes.

    Science.gov (United States)

    Yoon, Hye Eun; Mo, Eun Young; Shin, Seok Joon; Moon, Sung Dae; Han, Je Ho; Kim, Eun Sook

    2016-08-05

    This study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes. This cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (≥1720 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50 % of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed. Serum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles. Serum GGT levels were significantly associated with obesity, atherogenic dyslipidaemia, and metabolic syndrome, but not with the early and late stages of atherosclerotic vascular changes, in patients with type 2 diabetes. Serum GGT level may not be a reliable marker of subclinical atherosclerosis in type 2 diabetes.

  8. Factors of early atherosclerosis in patients with essential hypertension, obesity and comorbid subclinical hypothyroidism

    OpenAIRE

    Виктория Николаевна Плиговка; Юлия Николаевна Шапошникова

    2015-01-01

    The study identified the factors of early atherosclerosis in patients with essential hypertension and obesity and comorbid subclinical hypothyroidism.Aim: To identify factors that influence the development of atherosclerosis in patients with obesity, hypertension and comorbid subclinical hypothyroidism.Methods. The study involved 75 patients, including 53 patients in the phase of subclinical hypothyroidism and 22 patients in the phase of euthyroidism. All the patients underwent measurement of...

  9. Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

    Directory of Open Access Journals (Sweden)

    Piero Ruscitti

    Full Text Available Several studies showed the close relationship between Rheumatoid Arthritis (RA and cerebro-cardiovascular events (CVEs and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis.We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis.We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH, type 2 diabetes mellitus and metabolic syndrome (MS, at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis.Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

  10. 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 (mea......-risk individuals, suggesting added value of imaging for diagnosis and prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01410318....

  11. Genistein Supplementation Inhibits Atherosclerosis with Stabilization of the Lesions in Hypercholesterolemic Rabbits

    OpenAIRE

    Lee, Choong-Sik; Kwon, Su-Jin; Na, Sun-Young; Lim, Seung-Pyung; Lee, Jung-Hee

    2004-01-01

    The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion...

  12. [Analysis of carotid atherosclerosis and related risk factors in a university physical examination population in Beijing].

    Science.gov (United States)

    Meng, X F; Liu, G M; Wang, X L; Xu, Q

    2017-09-05

    Objective: To explore the incidence of carotid atherosclerosis in staffs of Tsinghua university according to the different age groups, the possible risk factors and conduct a follow-up survey. Methods: Detailed information about physical examination and carotid ultrasound from 832 staffs of Tsinghua University between 2014 to 2016 were reviewed to observe the occurrence and development of atherosclerosis according to different age groups; the correlation between conventional risk factors and carotid arteriosclerosis was studied by multivariate Logistic regression analysis.The process of different degrees of arteriosclerosis in the population was observed one year later. Results: In the past three years, there were 2 024 cases of carotid examination. Among them, there were 832 staffs who had been followed up for more than 6 months. There were 517 cases of carotid atherosclerosis, with 289 males (55.9%) and 228 females (44.1%), and the incidence of atherosclerosis in male was higher than that in female ( P 0.05). Conclusions: This research suggests that the incidence of atherosclerosis in male is higher than that in female, and hypertension, diabetes and hyperlipidemia are important influencing factors of arteriosclerosis for staffs of Tsinghua University. Early screening, identification of high-risk patients and comprehensive treatment should be done to delay the process of atherosclerosis.In addition, long-term follow-up is necessary in the context of no significant changes within the short-term.

  13. Subclinical atherosclerosis in menopausal women with low to medium calculated cardiovascular risk.

    Science.gov (United States)

    Lambrinoudaki, Irene; Armeni, Eleni; Georgiopoulos, Georgios; Kazani, Maria; Kouskouni, Evangelia; Creatsa, Maria; Alexandrou, Andreas; Fotiou, Stylianos; Papamichael, Christos; Stamatelopoulos, Kimon

    2013-03-20

    The menopausal status is closely related with cardiovascular disease (CVD). Nevertheless, it is still not included in risk stratification by total cardiovascular risk estimation systems. The present study aimed to evaluate the extent of subclinical vascular disorders in young healthy postmenopausal women. This cross-sectional study consecutively recruited 120 healthy postmenopausal women without clinically overt CVD or diabetes, aged 41-60 years and classified as not high-risk by the Heartscore (subclinical atherosclerosis. Subclinical atherosclerosis and the presence of at least one plaque were identified in 55% and 28% of women, respectively. Subjects with subclinical atherosclerosis had higher age, years since menopause, HOMA-IR and blood pressure. By multivariate analysis years since menopause and systolic blood pressure independently determined subclinical atherosclerosis while 79% of intermediate-risk women (Heartscore 2-4.9%) being in menopause for at least 4 years would be reclassified to a higher risk for the presence of atherosclerosis. Subclinical atherosclerosis was highly prevalent in postmenopausal women with low to medium Heartscore. Thus our data suggest that menopausal status and associated risk factors should be additionally weighted in risk calculations, regarding primary prevention strategies in this population. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Lisa R. Hoving

    2018-02-01

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

  15. Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Stephanie Maiwald

    Full Text Available Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out to unravel the molecular pathology in a large kindred with an autosomal dominant inherited form of premature atherosclerosis.Parametric linkage analysis was performed in a pedigree comprising 4 generations, of which a total of 11 members suffered from premature vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA (c.920C>G; p.Ser307Cys was identified. The variant was absent from nearly 28,000 individuals, including 2,571 patients with premature atherosclerosis. KERA, a proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic lesions, but not in healthy arterial specimens. Moreover, KERA expression in plaques was significantly associated with plaque size in a carotid-collar Apoe-/- mice (r2 = 0.69; p<0.0001.A rare variant in KERA was identified in a large kindred with premature atherosclerosis. The identification of KERA in atherosclerotic plaque specimen in humans and mice lends support to its potential role in atherosclerosis.

  16. 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.

  17. Monocyte angiotensin converting enzyme expression may be associated with atherosclerosis rather than arteriosclerosis in hemodialysis patients.

    Science.gov (United States)

    Ulrich, Christof; Seibert, Eric; Heine, Gunnar H; Fliser, Danilo; Girndt, Matthias

    2011-03-01

    Circulating monocytes can be divided into functionally distinct subpopulations according to their surface expression of CD14 and CD16. Monocytes with high-level expression of both antigens (CD14(++)CD16(+), Mo2 cells) are associated with cardiovascular morbidity and mortality in hemodialysis patients. These cells express angiotensin converting enzyme (ACE) on their surface. They are involved in the association of chronic inflammation and cardiovascular disease in kidney patients. Cardiovascular morbidity results from atherosclerosis (plaque-forming, vessel occluding disease) and arteriosclerosis (loss of arterial dampening function). It is unknown whether ACE-expressing proinflammatory monocytes are related to atherosclerosis, arteriosclerosis, or both. During baseline examination for a prospective study on monocyte ACE expression and mortality, 60 chronic hemodialysis patients of an academic outpatient center were screened for atherosclerosis by carotid artery ultrasound, for arteriosclerosis by pulse pressure measurement, and for ACE expression on Mo2 cells by flow cytometry. ACE expression on Mo2 monocytes was significantly higher in patients with severe compared with those with little or no carotid atherosclerosis. Mo2 ACE correlated with a score to semiquantify atherosclerosis and remained a significant predictor of carotid plaques in multivariate analysis including the other univariately associated variables of age, hemoglobin A1c, and albumin. Mo2 ACE was not related to pulse pressure. ACE expression on Mo2, although being a known predictor of mortality and cardiovascular disease in end-stage renal disease patients, may act via enhancement of atherosclerosis rather than arteriosclerosis.

  18. Pycnogenol® and Centella Asiatica for asymptomatic atherosclerosis progression.

    Science.gov (United States)

    Belcaro, G; Dugall, M; Hosoi, M; Ippolito, E; Cesarone, M; Luzzi, R; Cornelli, U; Ledda, A

    2014-02-01

    The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol and TECA (total triterpenic fraction of Centella Asiatica) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral non-stenosing plaques. This was an observational pilot substudy of the San Valentino epidemiological cardiovascular study. The study included 1363 subjects aged 45-60 without any conventional risk factors who had non stenosing atherosclerotic plaques (Centella Asiatica) 100 mg/day. There was a six monthly follow-up up to 30 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed from the non-stenotic to the stenotic group. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 30 months. The ultrasonic score increased significantly in groups 1, 2 and 4 but not in groups 3, 5 and 6 suggesting a beneficial effect of Pycnogenol 100 mg. The percentage of plaques that progressed from class IV to class V was 8.4% in group 2, 5.3% in group 3, 4% in group 5 and 1.1% in group 6 (P<0.0001) compared with 16.6% in group 4 (aspirin) and 21.3% in the control group suggesting a beneficial effect of Pycnogenol. The lowest rate of progression was in group 6 (Pycnogenol plus TECA). At 30 months, the oxidative stress in all the Pycnogenol groups was less than in the control group. The oxidative stress was lower in the Pycnogenol 100 mg group than the Pycnogenol 50 mg group (P<0.0001). In the combined group of Pycnogenol and TECA the oxidative stress was less than the Pycnogenol alone (P<0.001). Pycnogenol and the combination of Pycnogenol+TECA appear to reduce the progression of subclinical arterial lesions in low-risk asymptomatic subjects. The reduction in plaque progression was associated with a reduction in oxidative stress. The results justify a large randomized controlled study to demonstrate the efficacy of the

  19. Significance of good collateral compensation in symptomatic intracranial atherosclerosis.

    Science.gov (United States)

    Lau, Alexander Y L; Wong, Edward H C; Wong, Adrian; Mok, Vincent C T; Leung, Thomas W; Wong, Ka-sing Lawrence

    2012-01-01

    Collateral circulation stabilizes cerebral blood flow in patients with acute occlusion, but its prognostic role is less studied in intracranial atherosclerosis and appears different in moderate to severe stenosis. We aimed to study the associations between antegrade flow across stenosis, collateral flow via leptomeningeal anastomosis, and the neurological outcome and recurrence risk in patients with symptomatic intracranial stenosis. We examined a cohort of consecutive patients admitted for stroke or transient ischemic attack (TIA) with symptomatic intracranial stenosis confirmed by digital subtraction angiography in a single-center retrospective study. Angiograms were graded systematically in a blinded fashion for antegrade and collateral flow, using Thrombolysis in Cerebral Infarction (TICI) and American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading, respectively, and integrated to a simple composite circulation score. Demographic and clinical variables, modified Rankin Scale (mRS) scores at 3 months, recurrent stroke or TIA in 12 months were collected. Uni- and multivariate analyses were performed to identify independent predictors of good outcome (mRS 0-2) and recurrence in a logistic regression model. Among 69 patients with pure intracranial atherosclerosis ≥ 50%, compromised antegrade flow (TICI 0-2a) was observed in 26 (36%) patients and was associated with more severe arterial stenosis (mean 86 vs. 74%, p = 0.001). Poor collateral compensation resulting in a poor composite circulation score was observed in 8 (12%) patients. Patients with a good circulation score (n = 61, 88%) had preserved flow, which was associated with more favorable outcome (OR 7.50, 95% CI 1.11-50.7, p = 0.04) and less recurrent TIA or stroke (OR 0.18, 95% CI 0.04-0.96, p = 0.04). Prognosis was not significantly associated with antegrade or collateral grade per se. Good collateral compensations are more important in

  20. Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes.

    Science.gov (United States)

    Aengevaeren, Vincent L; Mosterd, Arend; Braber, Thijs L; Prakken, Niek H J; Doevendans, Pieter A; Grobbee, Diederick E; Thompson, Paul D; Eijsvogels, Thijs M H; Velthuis, Birgitta K

    2017-07-11

    Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis. Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants' activity was categorized as 2000 MET-min/wk. A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3-145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0-60.9] versus 0 [interquartile range, 0-43.5]; P=0.02) and prevalence of CAC (68%; adjusted odds ratio [ORadjusted]=3.2; 95% confidence interval [CI], 1.6-6.6) and plaque (77%; ORadjusted=3.3; 95% CI, 1.6-7.1) compared with exercise (≥9 MET) was associated with CAC (ORadjusted=1.47; 95% CI, 1.14-1.91) and plaque (ORadjusted=1.56; 95% CI, 1.17-2.08). Among participants with CAC>0, there was no difference in CAC score (P=0.20), area (P=0.21), density (P=0.25), and regions of interest (P=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; ORadjusted=0.35; 95% CI, 0.15-0.85) and more often had only calcified plaques (38% versus 16%; ORadjusted=3.57; 95% CI, 1.28-9.97) compared with the least active group (2000 MET-min/wk group had a higher

  1. CD98 regulates vascular smooth muscle cell proliferation in atherosclerosis.

    Science.gov (United States)

    Baumer, Yvonne; McCurdy, Sara; Alcala, Martin; Mehta, Nehal; Lee, Bog-Hieu; Ginsberg, Mark H; Boisvert, William A

    2017-01-01

    Vascular smooth muscle cells (VSMC) migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. CD98 is a transmembrane protein made of two subunits, CD98 heavy chain (CD98hc) and one of six light chains, and is known to be involved in cell proliferation and survival. Because the influence of CD98hc on atherosclerosis development is unknown, our aim was to determine if CD98hc expressed on VSMC plays a role in shaping the morphology of atherosclerotic plaques by regulating VSMC function. In addition to determining the role of CD98hc in VSMC proliferation and apoptosis, we utilized mice with SMC-specific deletion of CD98hc (CD98hc(fl/fl)SM22αCre(+)) to determine the effects of CD98hc deficiency on VSMC function in atherosclerotic plaque. After culturing for 5 days in vitro, CD98hc(-/-) VSMC displayed dramatically reduced cell counts, reduced proliferation, as well as reduced migration compared to control VSMC. Analysis of aortic VSCM after 8 weeks of HFD showed a reduction in CD98hc(-/-) VSMC proliferation as well as increased apoptosis compared to controls. A long-term atherosclerosis study using SMC-CD98hc(-/-)/ldlr(-/-) mice was performed. Although total plaque area was unchanged, CD98hc(-/-) mice showed reduced presence of VSMC within the plaque (2.1 ± 0.4% vs. 4.3 ± 0.4% SM22α-positive area per plaque area, p < 0.05), decreased collagen content, as well as increased necrotic core area (25.8 ± 1.9% vs. 10.9 ± 1.6%, p < 0.05) compared to control ldlr(-/-) mice. We conclude that CD98hc is required for VSMC proliferation, and that its deficiency leads to significantly reduced presence of VSMC in the neointima. Thus, CD98hc expression in VSMC contributes to the formation of plaques that are morphologically more stable, and thereby protects against atherothrombosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Serial Coronary Imaging of Early Atherosclerosis Development in Fast-Food-Fed Diabetic and Nondiabetic Swine

    Directory of Open Access Journals (Sweden)

    Nienke S. van Ditzhuijzen, MSc

    2016-10-01

    Full Text Available Patients with diabetes mellitus (DM are at increased risk for atherosclerosis-related events compared to non-DM (NDM patients. With an expected worldwide epidemic of DM, early detection of anatomic and functional coronary atherosclerotic changes is gaining attention. To improve our understanding of early atherosclerosis development, we studied a swine model that gradually developed coronary atherosclerosis. Interestingly, optical coherence tomography, near-infrared spectroscopy (NIRS, vascular function, and histology demonstrated no differences between development of early atherosclerosis in fast-food-fed (FF DM swine and that in FF-NDM swine. Coronary computed tomography angiography did not detect early atherosclerosis, but optical coherence tomography and near-infrared spectroscopy demonstrated coronary atherosclerosis development in FF-DM and FF-NDM swine.

  3. Operationalizing Frailty in the Atherosclerosis Risk in Communities Study Cohort.

    Science.gov (United States)

    Kucharska-Newton, Anna M; Palta, Priya; Burgard, Sheila; Griswold, Michael E; Lund, Jennifer L; Capistrant, Benjamin D; Kritchevsky, Stephen B; Bandeen-Roche, Karen; Windham, B Gwen

    2017-03-01

    Factors that may contribute to the development of frailty in late life have not been widely investigated. The Atherosclerosis Risk in Communities (ARIC) Study cohort presents an opportunity to examine relationships of midlife risk factors with frailty in late life. However, we first present findings on the validation of an established frailty phenotype in this predominantly biracial population of older adults. Among 6,080 participants, we defined frailty based upon the Cardiovascular Health Study (CHS) criteria incorporating measures of weight loss, exhaustion, slow walking speed, low physical activity, and low grip strength. Criterion and predictive validity of the frailty phenotype were estimated from associations between frailty status and participants' physical and mental health status, physiologic markers, and incident clinical outcomes. A total of 393 (6.5%) participants were classified as frail and 50.4% pre-frail, similar to CHS (6.9% frail, 46.6% pre-frail). In age-adjusted analyses, frailty was concurrently associated with depressive symptoms, low self-rated health, low medication adherence, and clinical biomarker levels (ie, cholesterol, hemoglobin A1c, white blood cell count, C-reactive protein, and hemoglobin). During 1-year follow-up, frailty was associated with falls, low physical ability, fatigue, and mortality. These findings support the validity of the CHS frailty phenotype in the ARIC Study cohort. Future studies in ARIC may elucidate early-life exposures that contribute to late-life frailty.

  4. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    Science.gov (United States)

    Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

    2015-03-18

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

  5. [Lipoprotein(a) is associated to atherosclerosis in primary hypercholesterolemia].

    Science.gov (United States)

    Bea, Ana M; Mateo-Gallego, Rocío; Jarauta, Estíbaliz; Villa-Pobo, Rosa; Calmarza, Pilar; Lamiquiz-Moneo, Itziar; Cenarro, Ana; Civeira, Fernando

    2014-01-01

    Several studies have suggested that Lp(a) could be a risk factor mainly in hypercholesterolemic patients. A total of 909 individuals were selected for this study. 307 were diagnosed of familiar hypercholesterolemia with a pathogenic mutation in LDLR or APOB genes (FH+), 291 of familiar combined hyperlipidemia (FCH) and 311 of familial hypercholesterolemia without a pathogenic mutation in LDLR nor APOB genes (FH-). Main risk factor were studied, included statin treatment. Plasma lipids, Lp(a), HbA1c and C-reactive protein. Intima-media thickness (IMT) of common and bulb carotid in both sides were measured in all subjects. Lp(a) values (median, interquartile range) were 21.9mg/dL (9.24-50.5) in FH+, 22.4mg/dL (6.56-51.6) in FCH and 32.7 (14.6-71.5) in FH- (P50mg/dL (17.9%) than in subjects with Lp(a) 50mg/dL, respectively). Our results indicate that Lp(a) is associated with atherosclerosis burden especially in subjects with FH- and concentrations of Lp(a)>50mg/dL. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  6. Plasma oxygen permeability may be a factor in atherosclerosis.

    Science.gov (United States)

    Heppner, Bradley T; Morgan, Louis Wm

    2004-01-01

    Plasma oxygen permeability measures how easily oxygen dissolves in and diffuses through blood plasma. There has long been evidence that artery wall hypoxia plays a role in atherogenesis. This paper reviews the influence that plasma oxygen permeability has on artery wall oxygenation and presents experimental evidence for a relationship between plasma oxygen permeability and clinically significant obstructive coronary artery disease. Thirty-eight inpatients referred for diagnostic cardiac catheterization were scored for active coronary artery disease, and their plasma oxygen permeabilities were measured. There was a statistically significant (p = 0.04) correlation between active coronary artery disease and plasma oxygen permeability. There were also statistically significant differences in mean plasma oxygen permeability both between patients who did and did not have actively progressing coronary artery disease (p = 0.01) and between patients who did and did not have clinically significant obstructive coronary artery disease, whether it was actively progressing or not (p = 0.02). These findings suggest that a decline in plasma oxygen permeability may be one of the many factors associated with progression of atherosclerosis and that substances which increase oxygen permeability might offer a useful adjunct to current therapeutic measures.

  7. Inflammatory markers and extent and progression of early atherosclerosis

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT......) in the general population. METHODS: Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were...... calculated within each study and then combined using random-effects meta-analyses. RESULTS: Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between...

  8. Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis?

    Science.gov (United States)

    Kunnen, Sandra; Van Eck, Miranda

    2012-01-01

    Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme that catalyzes the esterification of free cholesterol in plasma lipoproteins and plays a critical role in high-density lipoprotein (HDL) metabolism. Deficiency leads to accumulation of nascent preβ-HDL due to impaired maturation of HDL particles, whereas enhanced expression is associated with the formation of large, apoE-rich HDL1 particles. In addition to its function in HDL metabolism, LCAT was believed to be an important driving force behind macrophage reverse cholesterol transport (RCT) and, therefore, has been a subject of great interest in cardiovascular research since its discovery in 1962. Although half a century has passed, the importance of LCAT for atheroprotection is still under intense debate. This review provides a comprehensive overview of the insights that have been gained in the past 50 years on the biochemistry of LCAT, the role of LCAT in lipoprotein metabolism and the pathogenesis of atherosclerosis in animal models, and its impact on cardiovascular disease in humans. PMID:22566575

  9. Increased subclinical atherosclerosis in patients with chronic plaque psoriasis.

    Science.gov (United States)

    Evensen, Kristin; Slevolden, Ellen; Skagen, Karolina; Rønning, Ole Morten; Brunborg, Cathrine; Krogstad, Anne-Lene; Russell, David

    2014-12-01

    Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Comparison of automatic atherosclerosis identification methods on MR imagery

    Science.gov (United States)

    Carman, Charles S.; Merickel, Michael B.

    1990-07-01

    Magnetic resonance imaging (MRI) provides excellent soft tissue contrast enabling the non-invasive visualization of soft lissue diseases. The quantification of tissues distinguishable in MR images significantly increases the diagnostic information available to physicians. New 3-D display workstations are available that can also make use of the tissue characteristics to generate clinically useful views of a patient. While simple tissue selection methods work with computed tomography (CT) images these same methods usually do not work with MR images. Several feasibility studies of tissue classification methods have been performed on MR images but few comparative studies of these methods have been published and little work is available on the best statistical model of tissues in MIRI. We have developed a novel method for the identification and quantification of soft tissues from MRI atherosclerosis in particular. This project is part of our work on the development of tissue characterization and identification tools to facilitate soft tissue disease diagnosis and evaluation utilizing MR imagery. Several supervised pattern recognition methods were investigated for tissue identification in MR images such as a Fisher linear discriminant and a minimum distance to the means classifier. For tissue in vivo adequate histology can be difficult to collect. We used cluster analysis methods to generate the necessary training information. ISODATA was modified to use hierarchical stopping rules to determine the true number of tissues in the images. This new method was

  11. STAT4 contributes to adipose tissue inflammation and atherosclerosis.

    Science.gov (United States)

    Dobrian, A D; Hatcher, M A; Brotman, J J; Galkina, E V; Taghavie-Moghadam, P; Pei, H; Haynes, B A; Nadler, J L

    2015-10-01

    Adipose tissue (AT) inflammation is an emerging factor contributing to cardiovascular disease. STAT4 is a transcription factor expressed in adipocytes and in immune cells and contributes to AT inflammation and insulin resistance in obesity. The objective of this study was to determine the effect of STAT4 deficiency on visceral and peri-aortic AT inflammation in a model of atherosclerosis without obesity. Stat4(-/-)Apoe(-/-) mice and Apoe(-/-) controls were kept either on chow or Western diet for 12 weeks. Visceral and peri-aortic AT were collected and analyzed for immune composition by flow cytometry and for cytokine/chemokine expression by real-time PCR. Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice had similar body weight, plasma glucose, and lipids. Western diet significantly increased macrophage, CD4+, CD8+, and NK cells in peri-aortic and visceral fat in Apoe(-/-) mice. In contrast, in Stat4(-/-)Apoe(-/-) mice, a Western diet failed to increase the percentage of immune cells infiltrating the AT. Also, IL12p40, TNFa, CCL5, CXCL10, and CX3CL1 were significantly reduced in the peri-aortic fat in Stat4(-/-)Apoe(-/-) mice. Importantly, Stat4(-/-)Apoe(-/-) mice on a Western diet had significantly reduced plaque burden vs Apoe(-/-) controls. In conclusion, STAT4 deletion reduces inflammation in peri-vascular and visceral AT and this may contribute via direct or indirect effects to reduced atheroma formation. © 2015 Society for Endocrinology.

  12. Fluorescence spectroscopic detection of early injury-induced atherosclerosis

    Science.gov (United States)

    Lucas, Alexandra; Perk, Masis; Wen, Yue; Smith, Carol

    1992-08-01

    Laser-induced fluorescence spectroscopy has been used for the detection of advanced atherosclerotic lesions. Angioplasty balloon-mediated injury was examined spectroscopically in order to assess the sensitivity of fluorescence spectroscopy for detection of early atherosclerosis. Abdominal aortic balloon angioplasty was performed via femoral artery cutdown in nine White Leghorn roosters (five normal, four atherogenic diet). Roosters were sacrificed at 1, 2, 4, 8, and 12 week intervals. Fluorescence emission spectra (n equals 114) were recorded from each aortic section (XeCl excimer laser, 308 nm, 1.5 - 2.0 mJ/pulse, 5 Hz). Changes in normalized fluorescence emission intensity were correlated with selected sections of histology. All balloon-injured segments showed intimal fibrous proliferation. For intimal thickness measuring > 70 (mu) , fluorescence emission intensity was decreased at 440 - 460 nm (p Lesions complicated by thrombus also had lower fluorescence emission at 425 - 450 nm when compared to histologically normal aorta (p muscular (abdominal) aorta (p muscular abdominal aorta.

  13. 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.

  14. Coagulation and the vessel wall in thrombosis and atherosclerosis.

    Science.gov (United States)

    Kleinegris, Marie-Claire; Ten Cate-Hoek, Arina J; Ten Cate, Hugo

    2012-01-01

    The blood coagulation system is a key survival mechanism that has developed to protect man against lethal bleeding. A second function of blood coagulation is its close interaction with immunity. The immune-mediated coagulation responses may broadly be regarded as an element of response to injury. Pathological coagulation responses, including thromboembolism and disseminated intravascular coagulation (DIC), could therefore be regarded as excessive immune responses to a vessel wall injury. Virchow's triad, which comprises changes in the components of the blood, the state of the vessel wall, and the blood flow, was originally proposed for venous thrombosis. However, lately it appears that the same principles can be applied to arterial thrombosis and even DIC. It has even been postulated that all forms of thrombosis may be part of a continuous spectrum of the same disease. Over the past few years, an accumulation of evidence has shown that the etiopathogenetic mechanisms behind venous and arterial thrombosis are quite similar. The traditional elements of Virchow's triad are found to apply to both arterial and venous thrombosis. Yet, nowadays more emphasis is placed on the vessel wall and vascular bed specificity and the interaction with inflammation and hypercoagulability. This narrative review will discuss recent advances in research on the possible interactions between coagulation, the vascular endothelium, and atherosclerosis as well as the consequences of such interactions for venous and arterial thrombosis.

  15. Gout in Older Adults: The Atherosclerosis Risk in Communities Study

    Science.gov (United States)

    Burke, Bridget Teevan; Köttgen, Anna; Law, Andrew; Grams, Morgan; Baer, Alan N.; Coresh, Josef

    2016-01-01

    Background: It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. Methods: We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population–based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. Results: The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63–6.63) increased gout risk in older age. Conclusions: These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age. PMID:26714568

  16. Long-term exposure to ambient particulate matter and prevalence of subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Diez Roux, Ana V; Auchincloss, Amy H; Franklin, Tracy Green; Raghunathan, Trivellore; Barr, R Graham; Kaufman, Joel; Astor, Brad; Keeler, Jerry

    2008-03-15

    Exposure to airborne particulate matter has been linked to cardiovascular events. Whether this finding reflects an effect of particulate matter exposure on the triggering of events or development of atherosclerosis remains unknown. Using data from the Multi-Ethnic Study of Atherosclerosis collected at baseline (2000-2002), the authors investigated associations of 20-year exposures to particulate matter with measures of subclinical disease (coronary calcium, common carotid intimal-medial thickness, and ankle-brachial index) in 5,172 US adults without clinical cardiovascular disease. Particulate matter exposures for the 20 years prior to assessment of subclinical disease were obtained from a space-time model of Environmental Protection Agency monitor data linked to residential history data for each participant. Intimal-medial thickness was weakly, positively associated with exposures to particulate matter aerodynamic diameter and aerodynamic diameter after controlling for age, sex, race/ethnicity, socioeconomic factors, diet, smoking, physical activity, blood lipids, diabetes, hypertension, and body mass index (1-4% increase per 21-microg/m(3) increase in particulate matter aerodynamic diameter or a 12.5-microg/m(3) increase in particulate matter aerodynamic diameter). No consistent associations with other measures of atherosclerosis were observed. There was no evidence of effect modification by sociodemographic factors, lipid status, smoking, diabetes, body mass index, or site. Results are compatible with some effect of particulate matter exposures on development of carotid atherosclerosis.

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

    Directory of Open Access Journals (Sweden)

    Nels C Olson

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

  18. The Circle of Willis and White Matter Lesions in Patients with Carotid Atherosclerosis.

    Science.gov (United States)

    Li, Hua; Xiong, Yunyun; Xu, Gelin; Zhang, Renliang; Zhu, Wusheng; Yin, Qin; Ma, Minmin; Fan, Xiaobing; Yang, Fang; Liu, Wenhua; Duan, Zuowei; Liu, Xinfeng

    2015-08-01

    The correlation between cerebral atherosclerosis and white matter lesions (WMLs) in the elderly was controversial in the published articles, where the stenosis was often evaluated by ultrasonography, computed tomography angiography, or magnetic resonance angiography and collaterals were seldom considered. We hypothesized that collaterals influence WMLs. Our study was to explore the relationship between the circle of Willis and WMLs in a retrospective, hospital-based cohort of patients with carotid atherosclerosis. Two hundred eighty-six patients with carotid atherosclerosis were enrolled from the Nanjing Stroke Registry. They underwent magnetic resonance imaging evaluating WMLs and digital subtraction angiography evaluating both carotid atherosclerosis and collateral capacity of the circle of Willis. We tested the association between severe carotid atherosclerosis, the circle of Willis, and WMLs by logistic regression analysis. Severity of carotid atherosclerosis was not significantly associated with either periventricular or deep WMLs (P = .656 and .566, respectively). Number of carotid arteries with severe stenosis was not associated with the severity of either periventricular or deep WMLs (P = .721 and .263, respectively). Patency of the communicating arteries (CoA) was not associated with periventricular or deep WMLs (P = .561 and .703, respectively). Advanced age and hypertension were associated with periventricular WMLs (P = .001 and .008, respectively). Advanced age, hypertension, and prior stroke were associated with deep WMLs (P = .049, .048, and .001, respectively). The circle of Willis and severe carotid atherosclerosis may not be related to WMLs. Further larger studies are warranted to confirm or refute our findings. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Leukotriene A4 hydrolase haplotype, diet and atherosclerosis: a twin study.

    Science.gov (United States)

    Zhao, Jinying; Goldberg, Jack; Vaccarino, Viola

    2013-01-01

    Atherosclerosis is an inflammatory process resulting from the interaction between genetic and environmental factors. Leukotrienes are inflammatory mediators generated from arachidonic acid, and genetic polymorphisms involved in leukotriene metabolism are implicated in atherosclerosis. The objectives of this study are to examine whether genetic variants in key leukotriene enzymes are associated with atherosclerosis, and whether dietary intake of competing leukotriene substrates modifies the effect of leukotriene variants on atherosclerosis. Atherosclerosis was assessed by common carotid intima-media thickness (IMT) using ultrasound. Sequence variants within arachidonate 5-lipoxygenase activating protein (ALOX5AP) and leukotriene A4 hydrolase (LTA4H) genes were analyzed with 32 single nucleotide polymorphisms (SNPs) in 169 Caucasian twin pairs from the Vietnam Era Twin Registry. The associations between genetic polymorphisms and carotid atherosclerosis, and gene × diet interactions were examined by generalized estimating equation controlling for potential confounders. A six-SNP haplotype in LTA4H, designated HapE, was significantly associated with carotid IMT after adjusting for known coronary risk factors. Twins carrying HapE had a much lower IMT compared to twins not carrying (695 μm vs. 750 μm, p = 0.0007). Moreover, dietary intake of polyunsaturated fatty acids strongly augmented the cardioprotective effect of HapE among those with this haplotype but not those without, suggesting a haplotype × diet interaction (interaction P(HapE×n-3) = 0.03, P(HapE×n-6) = 0.015). We identified a novel leukotriene haplotype that appears to be protective toward subclinical atherosclerosis. This association is modified by dietary intake of polyunsaturated fatty acids. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Does elevated body mass modify the influence of postmenopausal estrogen replacement on atherosclerosis progression: results from the estrogen in the prevention of atherosclerosis trial.

    Science.gov (United States)

    Mack, Wendy J; Hameed, Afshan B; Xiang, Min; Roy, Subir; Slater, Cristin C; Stanczyk, Frank Z; Lobo, Rogerio A; Liu, Chao-ran; Liu, Ci-hua; Hodis, Howard N

    2003-05-01

    To determine whether the estrogen-related reduction in atherosclerosis progression demonstrated in the estrogen in the prevention of atherosclerosis trial (EPAT) is modified by body mass index (BMI). Subgroup analyses were performed using data from EPAT, a randomized, double-blind, placebo-controlled trial designed to determine whether unopposed 17beta-estradiol administered for a 2-year treatment period reduces the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary trial endpoint was the rate of change of common carotid artery intima-media thickness (IMT). In this subgroup analysis, the sample was divided into 122 women with BMIwomen with BMI> or =30 kg/m(2). Statistical analysis was performed using mixed general linear models to evaluate whether the treatment effects on IMT progression rates differed in the two BMI groups. There was no significant difference in the estradiol treatment effect on IMT progression rates between postmenopausal women with BMI or =30 kg/m(2) (P=0.52). In the 77 subjects who did not use lipid-lowering therapy, there was significant improvement in IMT with estradiol treatment that was evident in both BMI groups (P=0.48 for differences between BMI groups). In contrast to the epidemiological observation that obese postmenopausal women do not derive benefit from estrogen replacement therapy, results of this study indicate that estradiol treatment is beneficial in preventing progression of atherosclerosis regardless of initial BMI. Estradiol treatment is beneficial in preventing progression of atherosclerosis in postmenopausal women not receiving lipid-lowering therapy, regardless of their initial body mass index.

  1. Nanostructure of Human Aortic Intima in Atherosclerosis (A Pilot Study

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2016-01-01

    Full Text Available Objective: to analyze the nanostructure of human aortic intima in atherosclerosis and demonstrate the poten tial effect of Niodex on cholesterol plaques.Materials and methods. Samples of intima were taken from those parts of aorta, where different stages of atherosclerotic chages were obvious. Aortic samples were incubated in a solution containing cyclodextrins. A solution of NIODEX, a propylene glycol ester of betacyclodextrin, was used in the study. A layer of aortic intima was formed on the glass slide surface with polylysine. The samples were placed into the working area of an atomicforce microscope (Integra Prima, NTMDT, Russian Federation, and their surfaces were scanned. The number of imaging points was 512; and the imaging regions were as follows: 100100 μm, 20002000 nm.Results. Classification of nanosurface objects was performed and typical fragments (craters, ridges, and trabecular fibers were identified, and quantitative assessment of their sizes was carried out. 27 fragments were identified as growing cholesterol plaques. 16 of them measuring 900—1200 nm were identified near ridges, and 11 near craters (600—1050 nm. Niodex caused destruction of lipid spots and smoothing of the intima surface. More than a half of the 27 identified objects (15 demostrated a 30% and more decrease in size (median 340—400 nm. A 10—15% decrease was registered in 7 fragments; in the remaining 5 fragments, the decrease in the lesion size was less than 10%.Conclusion. Raw data permit to suppose that the effect of Niodex on the aortic intima results in decceleartion and decreased intensity of atherosclerotic plaque growth on the intima fragments.

  2. LDL apheresis and inflammation--implications for atherosclerosis.

    Science.gov (United States)

    Hovland, A; Lappegård, K T; Mollnes, T E

    2012-09-01

    Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk patients when LDL cholesterol levels cannot be reduced adequately with medication. The treatment is highly effective, but could be affected by potential unwanted effects on pro- and anti-inflammatory biomarkers. In this paper, we review the literature regarding the effect of LDL apheresis on pro- and anti-inflammatory biomarkers important in atherosclerosis, also as patients in LDL apheresis have high risk for atherosclerotic complications. We discuss the effect of LDL apheresis on complement, cytokines and finally a group of other selected pro- and anti-inflammatory biomarkers. The complement system is affected by LDL apheresis, and there are differences between different LDL apheresis systems. The plasma separation columns seem to trigger the formation of proinflammatory complement factors including C3a and C5a, while the same anaphylatoxins are adsorbed by the LDL apheresis columns, however, to varying degree. Proinflammatory cytokines are to some extent adsorbed by the LDL apheresis columns, while some of the anti-inflammatory cytokines increase during treatment. Finally, we discuss the effect of apheresis on different biomarkers including C-reactive protein, fibrinogen, adhesion molecules, myeloperoxidase and HDL cholesterol. In conclusion, even if there are differences between pro- and anti-inflammatory biomarkers during LDL apheresis, the consequences for the patients are largely unknown and larger studies need to be performed. Preferably, they should be comparing the effect of different LDL apheresis columns on the total inflammatory profile, and this should be related to clinical endpoints. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

  3. PCSK9 inhibitors in the current management of atherosclerosis.

    Science.gov (United States)

    Whayne, Thomas F

    The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors. These observations gave hints and awoke interest that it might be possible to prepare monoclonal antibodies to PCSK9 and decrease its activity, after which there should be more active LDL-C cell receptors. The rest is a fascinating story that currently has resulted in two PCSK9 inhibitors, alirocumab and evolocumab, which, on average, decrease LDL-C approximately 50%. Nevertheless, if there are no contraindications, statins remain the standard of prevention for the high-risk CV patient and this includes both secondary and primary prevention. The new inhibitors are for the patient that does not attain the desired target for LDL-C reduction while taking a maximum statin dose or who does not tolerate any statin dose whatsoever. Atherosclerosis can be considered a metabolic disease and the clinician needs to realize this and think more and more of CV prevention. These inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events. (United States). Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  4. ASYMMETRIC DIMETHYLARGININE LEVELS AND ATHEROSCLEROSIS MARKERS IN CUSHING SYNDROME.

    Science.gov (United States)

    Ozsurekci, Cemile Gulbas; Akturk, Mujde; Ozkan, Cigdem; Gulbahar, Ozlem; Altinova, Alev Eroglu; Yalcin, Muhittin; Arslan, Emre; Toruner, Fusun

    2016-09-01

    As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS. Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease-matched control subjects. Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P.05). We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS. ABI = ankle-brachial index Apo = apolipoprotein ADMA = asymmetric dimethylarginine BMI = body mass index CVD = cardiovascular disease CIMT = carotid intima-media thickness CS = Cushing syndrome DM = diabetes mellitus DDAH = dimethylarginine dimethylaminohydrolase ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein hsCRP = high-sensitive C-reactive protein HOMA-IR = homeostatic model assessment of insulin resistance HT = hypertension LDL = low-density lipoprotein Lp-PLA2 = lipoprotein-associated phospholipase A2 Lp-a = lipoprotein a NO = nitric oxide.

  5. Red yeast rice prevents atherosclerosis through regulating inflammatory signaling pathways.

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    Wu, Min; Zhang, Wen-Gao; Liu, Long-Tao

    2017-09-01

    To observe the effects of red yeast rice (RYR) on blood lipid levels, aortic atherosclerosis (AS), and plaque stability in apolipoprotein E gene knockout (ApoE-/-) mice. Twenty-four ApoE-/- mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups (n = 8 in each group): model group (ApoE-/- group), RYR group (ApoE-/- + RYR group), and simvastatin group (ApoE-/- + simvastatin group). Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured with enzyme-linked immunosorbent assay. The level of high sensitivity C-reaction protein (Hs-CRP) was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9 (MMP-9) and nuclear factor κB (NF-κB) in aorta were tested by immunohistochemistry. Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein (a), and apolipoprotein B100 in ApoE-/- mice (P<0.01). Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α (P<0.01). RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta. RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflflammatory signaling pathways.

  6. Erythrocyte-bound apolipoprotein B in atherosclerosis and mortality.

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    de Vries, Marijke A; van Santen, Selvetta S; Klop, Boudewijn; van der Meulen, Noëlle; van Vliet, Marjolein; van de Geijn, Gert-Jan M; van der Zwan-van Beek, Ellen M; Birnie, Erwin; Liem, Anho H; de Herder, Wouter W; Castro Cabezas, Manuel

    2017-04-01

    The binding of apolipoprotein (apo) B-containing lipoproteins to circulating erythrocytes (ery-apoB) is associated with a decreased prevalence of atherosclerosis. In this study, we evaluated ery-apoB as a possible prognostic factor in cardiovascular events and all-cause mortality, in a prospective cohort study. Ery-apoB was measured by flow cytometry in subjects with and without cardiovascular disease (CVD). The primary endpoint was the cardiovascular event rate. Secondary endpoints were all-cause mortality and the combined endpoint of all-cause mortality and cardiovascular events (any event rate). A Cox regression analysis with univariate and multivariate analyses and Kaplan-Meier survival analysis was performed. Follow-up data were available of 384 subjects. Subjects were divided according to high (> 2·0 au, n = 60), intermediate (0·2-2·0 au, n = 274) or low (mortality [HR 9·9 (1·2-79·0), P = 0·031] and any event rate [HR 3·4 (95% CI 1·3-8·7), P = 0·012]. In a Cox regression analysis, only a history of CVD was significantly associated with any event rate [HR 3·6 (1·6-8·0), P = 0·002], while low ery-apoB showed a trend [HR 2·4 (0·9-6·4), P = 0·07]. In a subgroup analysis, in subjects with a history of CVD, ery-apoB was significantly associated with all-cause mortality (log rank P = 0·021) and any event rate (log rank P = 0·009). Low ery-apoB is associated with increased mortality and cardiovascular risk, especially in patients with a prior history of CVD. These subjects may benefit from more aggressive secondary prevention treatment. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  7. 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.

  8. 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.

  9. Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis.

    Science.gov (United States)

    Geer, J. C.; Crago, C. A.; Little, W. C.; Gardner, L. L.; Bishop, S. P.

    1980-01-01

    atherosclerosis are distinctive and can be distinguished from myocardial necrosis or fibrosis associated with acute total occlusion of a coronary artery. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 1 Figure 2 Figure 9 Figure 10 Figure 3 Figure 4 PMID:7361850

  10. Family history of diabetes and the risk of subclinical atherosclerosis.

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    Park, G-M; Cho, Y-R; Lee, S-W; Yun, S-C; Gil, E H; Kim, D W; Kim, T-S; Kim, C J; Cho, J S; Park, M-W; Her, S H; Kim, Y-H; Yang, D H; Kang, J-W; Lim, T-H; Jung, C H; Koh, E H; Lee, W J; Kim, M-S; Lee, K-U; Kim, H-K; Choe, J; Park, J-Y

    2016-06-01

    This study investigated the influence of a family history of diabetes on the risk of subclinical coronary atherosclerosis according to coronary computed tomography angiography (CCTA) in asymptomatic individuals. A total of 6434 consecutive asymptomatic individuals with no prior history of coronary artery disease voluntarily underwent CCTA evaluation as part of a general health examination. Coronary atherosclerotic plaque and significant coronary artery stenosis (degree of stenosis ≥50%) on CCTA were assessed. Logistic regression analysis was used to determine the association between a family history of diabetes and atherosclerotic plaque or significant coronary artery stenosis according to the degree of diabetes (normal, prediabetic and diabetic). Mean age of study participants was 53.7±7.6 years, and 4694 (73.0%) were male. A total of 1593 (24.8%) participants had a family history of diabetes in a first-degree relative. Among the study participants, 1115 (17.3%), 3122 (48.5%) and 2197 (34.1%) were categorized as diabetic, prediabetic and normal, respectively. In diabetic participants, after stepwise adjustments for clinical and laboratory variables, a family history of diabetes was significantly associated with non-calcified plaque (P0.05 for all). In prediabetic and normal participants, a family history of diabetes was not associated with either atherosclerotic plaque or significant coronary artery stenosis (P>0.05 for all). In asymptomatic diabetic individuals, a family history of diabetes is consistently associated with non-calcified coronary plaque after adjusting for risk factors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. p62-enriched inclusion bodies in macrophages protect against atherosclerosis

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    Sergin, Ismail; Bhattacharya, Somashubhra; Emanuel, Roy; Esen, Emel; Stokes, Carl J.; Evans, Trent D.; Arif, Batool; Curci, John A.; Razani, Babak

    2016-01-01

    Autophagy is a catabolic cellular mechanism that degrades dysfunctional proteins and organelles. Atherosclerotic plaque formation is enhanced in mice with macrophages that cannot undergo autophagy because of a deficiency of an autophagy component such as ATG5. We showed that exposure of macrophages to atherogenic lipids led to an increase in the abundance of the autophagy chaperone p62, which colocalized with polyubiquitinated proteins in cytoplasmic inclusions. p62 accumulation was increased in ATG5-null macrophages, which had large cytoplasmic ubiquitin-positive p62 inclusions. Aortas from atherosclerotic mice and plaques from human endarterectomy samples showed increased abundance of p62 and polyubiquitinated proteins that co-localized with plaque macrophages, suggesting that p62-enriched protein aggregates were characteristic of atherosclerosis. The formation of the cytoplasmic inclusions depended on p62 because lipid-loaded p62-null macrophages accumulated polyubiquitinated proteins in a diffuse cytoplasmic pattern. The failure of these aggregates to form was associated with increased secretion of IL-1β and enhanced macrophage apoptosis, which depended on the p62 ubiquitin-binding domain and at least partly involved p62-mediated clearance of NLRP3 inflammasomes. Consistent with our in vitro observations, p62-deficient mice formed greater numbers of more complex atherosclerotic plaques, and p62 deficiency further increased atherosclerotic plaque burden in mice with a macrophage-specific ablation of ATG5. Together, these data suggested that sequestration of cytotoxic ubiquitinated proteins by p62 protects against atherogenesis, a condition in which the clearance of protein aggregates is disrupted. PMID:26732762

  12. Male-specific association between a gamma-secretase polymorphism and premature coronary atherosclerosis.

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    Karen M J van Loo

    Full Text Available BACKGROUND: Atherosclerosis is a common multifactorial disease resulting from an interaction between susceptibility genes and environmental factors. The causative genes that contribute to atherosclerosis are elusive. Based on recent findings with a Wistar rat model, we speculated that the gamma-secretase pathway may be associated with atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: We have tested for association of premature coronary atherosclerosis with a non-synonymous single-nucleotide polymorphism (SNP in the gamma-secretase component APH1B (Phe217Leu; rs1047552, a SNP previously linked to Alzheimer's disease. Analysis of a Dutch Caucasian cohort (780 cases; 1414 controls showed a higher prevalence of the risk allele in the patients (odds ratio (OR = 1.35, albeit not statistically different from the control population. Intriguingly, after gender stratification, the difference was significant in males (OR = 1.63; p = 0.033, but not in females (OR = 0.50; p = 0.20. Since Phe217Leu-mutated APH1B showed reduced gamma-secretase activity in mouse embryonic fibroblasts, the genetic variation is likely functional. CONCLUSION/SIGNIFICANCE: We conclude that, in a male-specific manner, disturbed gamma-secretase signalling may play a role in the susceptibility for premature coronary atherosclerosis.

  13. Role of erythrocyte sedimentation rate in ischemic stroke as an inflammatory marker of carotid atherosclerosis

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    Amit Shankar Singh

    2014-01-01

    Full Text Available Background: Inflammation mediates a key role in the pathogenesis of atherosclerosis which is an important cause of ischemic stroke. An elevated erythrocyte sedimentation rate (ESR may, therefore, be a marker of the extent andor intensity of a general atherosclerotic process and thus a marker for advanced atherosclerosis heralding increased risk of arterial thrombosis leading to ischemic stroke. Materials and Methods: ESR was calculated in ischemic stroke patients by Westergren′s method along with carotid sonography using high resolution 7.5 MHz techniques to find the prevalence of increased carotid intima-media thickness (CIMT and presence of plaque according to Mannheim Carotid Intima-Media Thickness Consensus. Results: Average value of ESR in all patients was 27.89 ΁ 9.73 mm/h. A significant association was found between ESR and markers of carotid atherosclerosis, that is, high CIMT of more than 0.8 mm (P < 0.0001 and presence of plaque (P-0.026 in univariate analysis. Also, a significant positive correlation was found between ESR and serum fibrinogen, another inflammatory marker. (r = 0.88, P < 0.0001. Conclusion: The extent of inflammation may reflect in part the propensity of atherosclerotic lesions to lead to clinical disease. Study shows the association of ESR with markers of atherosclerosis confirming the strength of the inflammatory response associated with carotid atherosclerosis and might conceivably carry important prognostic information regarding occurrence of such catastrophic events in future.

  14. ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

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    Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

    2015-06-01

    Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

  15. 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.

  16. Characterization of intravascular cellular activation in relationship to subclinical atherosclerosis in postmenopausal women.

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    Jayachandran, Muthuvel; Garovic, Vesna D; Mielke, Michelle M; Bailey, Kent R; Lahr, Brian D; Miller, Virginia M

    2017-01-01

    Mechanisms and interactions among intravascular cells contributing to development of subclinical atherosclerosis are poorly understood. In women, both menopausal status and pregnancy history influence progression of atherosclerosis. This study examined activation and interactions among blood elements with subclinical atherosclerosis in menopausal women with known pregnancy histories. Carotid intima-media thickness (CIMT), as a marker of subclinical atherosclerosis, was measured using B-mode ultrasound in age- and parity-matched women [40 with and 40 without a history of preeclampsia] 35 years after the index pregnancy. Interactions among intravascular cells (38 parameters) were measured by flow cytometry in venous blood. Data analysis was by principal component which retained 7 independent dimensions accounting for 63% of the variability among 38 parameters. CIMT was significantly greater in women with a history of preeclampsia (P = 0.004). Platelet aggregation and platelet interactions with granulocytes and monocytes positively associated with CIMT in postmenopausal women independent of their pregnancy history (ρ = 0.258, Psubclinical atherosclerosis differ in women depending upon their pregnancy histories.

  17. Correlation between vascular endothelial growth factor and subclinical atherosclerosis in patients with psoriasis.

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    Shahidi-Dadras, Mohammad; Haghighatkhah, Hamid Reza; Abdollahimajd, Fahimeh; Younespour, Shima; Partovi Kia, Masoud; Zargari, Omid

    2016-01-01

    Psoriasis is associated with increased risk of atherosclerotic disorders. Vascular endothelial growth factor (VEGF) is an angiogenic factor that was overexpressed in both psoriatic and atherosclerotic lesions. In a prospective controlled study, we investigated the correlation between serum levels of VEGF and subclinical atherosclerosis in patients with moderate to severe psoriasis. Sixty patients with moderate to severe psoriasis and 60 age- and gender-matched healthy controls were recruited to the study. Mean intima-media thickness of the common carotid artery (MIMT-CCA) and serum VEGF levels of all subjects were measured. Subclinical atherosclerosis was defined as having an MIMT-CCA ≥0.8 mm. Serum VEGF levels in psoriatic patients were significantly higher compared with healthy controls (P subclinical atherosclerosis (P subclinical atherosclerosis was significantly associated with serum VEGF levels, age, disease duration, and psoriasis area and severity index (PASI). This study supported the possible role of VEGF in the pathogenesis of subclinical atherosclerosis in psoriatic patients. © 2015 The International Society of Dermatology.

  18. Association of NAFLD with subclinical atherosclerosis and coronary-artery disease: meta-analysis.

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    Ampuero, Javier; Gallego-Durán, Rocío; Romero-Gómez, Manuel

    2015-01-01

    Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with increased risk of cardiovascular disease, using tests of subclinical atherosclerosis. To evaluate the influence of NAFLD on subclinical atherosclerosis and coronary artery disease (CAD). We reviewed Pubmed and EMBASE. According to inclusion and exclusion criteria, we selected 14 studies and were classified in two groups. Ten studies aimed the presence of subclinical atherosclerosis and four studies the presence of coronary artery disease. To assess subclinical atherosclerosis, we selected studies with pathological carotid intima-media thickness (CIMT) and with presence of carotid plaques. We considered coronary artery disease when patients showed at least 50% stenosis at one or more major coronary arteries. NAFLD was assessed by ultrasound (US) and liver biopsy. NAFLD showed a higher prevalence of pathological CIMT [35.1% (351/999) vs. 21.8% (207/948); p subclinical atherosclerosis and coronary artery disease. The right management of these patients could modify the natural history both liver and cardiovascular disease.

  19. Association of fatty liver with cardiovascular risk factors and subclinical atherosclerosis in a Mexican population.

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    Martínez-Alvarado, María Del Rocío; Juárez-Rojas, Juan Gabriel; Medina-Urrutia, Aída Xóchitl; Cardoso-Saldaña, Guillermo Celestino; González-Salazar, María Del Carmen; Posadas-Sánchez, Rosalinda; Jorge-Galarza, Esteban; Mendoza-Pérez, Enrique; Vargas-Alarcón, Gilberto; Posadas-Romero, Carlos

    2014-01-01

    Individuals with fatty liver (FL) have an increased risk of coronary artery disease (CAD) probably due to its association with cardiometabolic risk factors (CMRF). To know the prevalence of FL and analyze its association with CMRF and subclinical atherosclerosis, in a sample of Mexican Mestizo population. This study included 846 subjects from the Genetic of Atherosclerosis Disease (GEA) study (53 ± 9 years, 50.7% women) without diabetes and no personal or family history of premature CAD. Blood samples were taken for measurements of lipids profile, uric acid, and insulin. The presence of FL was identified by computed tomography. Carotid intima media thickness (CIMT) was measured by B mode ultrasound, using the > 75 percentile as cutoff value to define subclinical atherosclerosis. The general prevalence of FL was 32.4%. In men, FL was associated with hyperuricemia, whereas in women, hyperuricemia, low level of high density lipoprotein cholesterol, and metabolic syndrome were the factors associated with this hepatic alteration. In women, FL was associated with a 66% higher probability of having high CIMT, independently of age, hypertension, dyslipidemia, and waist circumference, but not of HOMA-IR. In women, FL was associated with the presence of subclinical atherosclerosis independently of traditional CMRF. Our study suggests that, in women, insulin resistance could be a mediator of metabolic abnormalities and of subclinical atherosclerosis.

  20. The interface of inflammation and subclinical atherosclerosis in granulomatosis with polyangiitis (Wegener's): a preliminary study.

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    Hajj-Ali, Rula A; Major, Jennifer; Langford, Carol; Hoffman, Garry S; Clark, Tiffany; Zhang, Li; Sun, Zhiyuan; Silverstein, Roy L

    2015-10-01

    The objective of this study is to assess the relationship between inflammatory disease in granulomatosis with polyangiitis (GPA, Wegener's) and the development of subclinical atherosclerosis. A total of 46 adult patients with GPA were enrolled. Disease status was measured by Birmingham vasculitis assessment scores as modified for GPA, vasculitis damage index, disease duration, and number of relapses. Classic atherosclerotic risk factors, platelet aggregation responses, and circulating microparticle (MP) levels were recorded. All patients underwent carotid artery intima-media thickness (IMT) measurement as outcome for subclinical atherosclerosis. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age were significantly associated with higher IMT (ρ values 0.37, 0.38, 0.35, and 0.054, respectively [P subclinical atherosclerosis. The correlation with subclinical atherosclerosis could be because of glucocorticoid use and not the inflammatory process in GPA, giving the inherent bias that exits with the use of glucocorticoid with each relapse. The findings of increased levels of circulating leukocyte-derived MPs and enhanced platelet reactivity during relapse suggest possible roles for MPs and platelets in disease pathogenesis and support a growing literature that links inflammation, atherosclerosis, and platelet activation. This hypothesis is further substantiated by our demonstration that MPs isolated from plasma of GPA patients can activate platelets and vascular endothelial cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Association between diabetic retinopathy and subclinical atherosclerosis in China: Results from a community-based study.

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    Liu, Yu; Teng, Xiangyu; Zhang, Wei; Zhang, Ruifeng; Liu, Wei

    2015-09-01

    To evaluate the association of diabetic retinopathy with subclinical atherosclerosis in middle-aged and elderly Chinese with type 2 diabetes. A cross-sectional community-based study was performed among 1607 patients aged 40 years or older in Shanghai. Non-mydriatic digital fundus photography examination was used in diabetic retinopathy detection. Presence of elevated carotid intima-media thickness or carotid plaque was defined as subclinical atherosclerosis. The prevalence of diabetic retinopathy was 15.1% in total patients. Patients with diabetic retinopathy were more likely to have elevated carotid intima-media thickness, carotid plaque and subclinical atherosclerosis than those without diabetic retinopathy (37.9% vs 30.7%, 57.6% vs 49.6% and 64.6% vs 57.1%, respectively). The presence of diabetic retinopathy was significantly associated with increased odds of subclinical atherosclerosis (odds ratio = 1.93, 95% confidence interval = 1.03-3.60) after full adjustments. The presence of diabetic retinopathy was significantly associated with subclinical atherosclerosis in middle-aged and elderly patients with type 2 diabetics in China. © The Author(s) 2015.

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

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    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.

  3. Niacin Suppresses Progression of Atherosclerosis by Inhibiting Vascular Inflammation and Apoptosis of Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Su, Gang; Sun, Guangli; Liu, Hai; Shu, Liliang; Zhang, Jingchao; Guo, Longhui; Huang, Chen; Xu, Jing

    2015-12-29

    BACKGROUND Niacin is a broad-spectrum lipid-regulating drug used for the clinical therapy of atherosclerosis; however, the mechanisms by which niacin ameliorates atherosclerosis are not clear. MATERIAL AND METHODS The effect of niacin on atherosclerosis was assessed by detection of atherosclerotic lesion area. Adhesion molecules in arterial endothelial cells were determined by using qRT-PCR and Western blot analysis. The levels of serum inflammatory cytokines in ApoE-/- mice were detected by using ELISA. We detected the expression levels of phosphorylated nuclear factors-kB (NF-κB) p65 in aortic endothelial cells of mice using Western blot analysis. Furthermore, we investigated the anti-inflammation effect and endothelium-protecting function of niacin and their regulatory mechanisms in vitro. RESULTS Niacin inhibited the progress of atherosclerosis and decreased the levels of serum inflammatory cytokines and adhesion molecules in ApoE-/- mice. Niacin suppressed the activity of NF-κB and apoptosis of vascular smooth muscle cells (VSMCs). Furthermore, niacin induced phosphorylated focal adhesion kinase (FAK) and FAK inhibitor PF-573228 reduced the level of Bcl-2 and elevated the level of cleaved caspase-3 in VSMCs. CONCLUSIONS Niacin inhibits vascular inflammation and apoptosis of VSMCs via inhibiting the NF-κB signaling and the FAK signaling pathway, respectively, thus protecting ApoE-/- mice against atherosclerosis.

  4. Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis.

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    Vilskersts, Reinis; Kuka, Janis; Liepinsh, Edgars; Makrecka-Kuka, Marina; Volska, Kristine; Makarova, Elina; Sevostjanovs, Eduards; Cirule, Helena; Grinberga, Solveiga; Dambrova, Maija

    2015-09-01

    The elevation of the levels of l-carnitine and its fatty acid esters, acylcarnitines, in tissue or plasma has been linked to the development of atherosclerosis. Recently, a potent inhibitor of l-carnitine biosynthesis and transport, methyl-γ-butyrobetaine (methyl-GBB), was discovered. In this study, we evaluated the effects of γ-butyrobetaine (GBB), l-carnitine and methyl-GBB administration on the progression of atherosclerosis. Apolipoprotein E knockout (apoE(-/-)) mice were treated with methyl-GBB, l-carnitine or GBB for 4months. Following the treatment, the amount of atherosclerotic lesions, the number of immune cells in atherosclerotic lesions and the plasma lipid profile were analysed. The l-carnitine and acylcarnitine levels were determined in the aortic tissues of CD-1 outbred mice 2weeks after treatment with methyl-GBB at the dose of 10mg/kg. Treatment with methyl-GBB decreased the acylcarnitine and l-carnitine levels in the aortic tissues by seventeen- and ten-fold, respectively. Methyl-GBB treatment at a dose of 10mg/kg reduced the size of atherosclerotic plaques by 36%. Neither l-carnitine nor GBB treatment affected the development of atherosclerosis. Methyl-GBB administration significantly attenuated the development of atherosclerosis in apoE(-/-)mice. Our results demonstrate that decreasing the acylcarnitine pools can attenuate the development of atherosclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 11β-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis.

    Science.gov (United States)

    Kipari, Tiina; Hadoke, Patrick W F; Iqbal, Javaid; Man, Tak-Yung; Miller, Eileen; Coutinho, Agnes E; Zhang, Zhenguang; Sullivan, Katie M; Mitic, Tijana; Livingstone, Dawn E W; Schrecker, Christopher; Samuel, Kay; White, Christopher I; Bouhlel, M Amine; Chinetti-Gbaguidi, Giulia; Staels, Bart; Andrew, Ruth; Walker, Brian R; Savill, John S; Chapman, Karen E; Seckl, Jonathan R

    2013-04-01

    11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11β-HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of 11β-HSD1 deficiency on atherosclerosis and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice were treated with a selective 11β-HSD1 inhibitor or crossed with 11β-HSD1-KO mice to generate double knockouts (DKOs) and challenged with an atherogenic Western diet. 11β-HSD1 inhibition or deficiency attenuated atherosclerosis (74-76%) without deleterious effects on plaque structure. This occurred without affecting plasma lipids or glucose, suggesting independence from classical metabolic risk factors. KO plaques were not more inflamed and indeed had 36% less T-cell infiltration, associated with 38% reduced circulating monocyte chemoattractant protein-1 (MCP-1) and 36% lower lesional vascular cell adhesion molecule-1 (VCAM-1). Bone marrow (BM) cells are key to the atheroprotection, since transplantation of DKO BM to irradiated ApoE-KO mice reduced atherosclerosis by 51%. 11β-HSD1-null macrophages show 76% enhanced cholesterol ester export. Thus, 11β-HSD1 deficiency reduces atherosclerosis without exaggerated lesional inflammation independent of metabolic risk factors. Selective 11β-HSD1 inhibitors promise novel antiatherosclerosis effects over and above their benefits for metabolic risk factors via effects on BM cells, plausibly macrophages.

  6. FAD286, an aldosterone synthase inhibitor, reduced atherosclerosis and inflammation in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Gamliel-Lazarovich, Aviva; Gantman, Anna; Coleman, Raymond; Jeng, Arco Y; Kaplan, Marielle; Keidar, Shlomo

    2010-09-01

    Aldosterone is known to be involved in atherosclerosis and cardiovascular disease and blockade of its receptor was shown to improve cardiovascular function. It was, therefore, hypothesized that inhibition of aldosterone synthesis would also reduce atherosclerosis development. To test this hypothesis, we examined the effect of FAD286 (FAD), an aldosterone synthase inhibitor, on the development of atherosclerosis in spontaneous atherosclerotic apolipoprotein E-deficient mice. Mice were divided into three treatment groups: normal diet, low-salt diet (LSD) and LSD treated with FAD at 30 mg/kg per day (LSD + FAD) for 10 weeks. Histomorphometry of the aortas obtained from these mice showed that atherosclerotic lesion area increased by three-fold under LSD compared with normal diet and FAD significantly reduced lesion area to values similar to normal diet. Changes in atherosclerosis were paralleled by changes in the expression of the inflammation markers (C-reactive protein, monocyte chemotactic protein-1, interleukin-6, nuclear factor kappa B and intercellular adhesion molecule-1) in peritoneal macrophages obtained from these mice. Surprisingly, whereas LSD increased serum or urine aldosterone levels, FAD did not alter these levels when evaluated at the end of the study. In J774A.1 macrophage-like cell line stimulated with lipopolysaccharide, FAD was shown to have a direct dose-dependent anti-inflammatory effect. In apolipoprotein E-deficient mice, FAD reduces atherosclerosis and inflammation. However, these actions appeared to be dissociated from its effect on inhibition of aldosterone synthesis.

  7. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects.

    Science.gov (United States)

    Chironi, Gilles; Simon, Alain; Hugel, Bénédicte; Del Pino, Muriel; Gariepy, Jérôme; Freyssinet, Jean-Marie; Tedgui, Alain

    2006-12-01

    To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk (Pmarkers or atherosclerosis. Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.

    Science.gov (United States)

    Fagman, Johan B; Wilhelmson, Anna S; Motta, Benedetta M; Pirazzi, Carlo; Alexanderson, Camilla; De Gendt, Karel; Verhoeven, Guido; Holmäng, Agneta; Anesten, Fredrik; Jansson, John-Olov; Levin, Malin; Borén, Jan; Ohlsson, Claes; Krettek, Alexandra; Romeo, Stefano; Tivesten, Åsa

    2015-04-01

    Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)-dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)-deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (-41%; thoracic aorta), subcutaneous fat mass (-44%), and cholesterol levels (-35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism. © FASEB.

  10. Matrix Metalloproteinases and Subclinical Atherosclerosis in Chronic Kidney Disease: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Andreas Kousios

    2016-01-01

    Full Text Available Background. Cardiovascular disease (CVD remains a significant problem in Chronic Kidney Disease (CKD. Subclinical atherosclerosis identified by noninvasive methods could improve CVD risk prediction in CKD but these methods are often unavailable. We therefore systematically reviewed whether circulating levels of Matrix Metalloproteinases (MMPs and tissue inhibitors (TIMPs are associated with subclinical atherosclerosis in CKD, as this would support their use as biomarkers or pharmacologic targets. Methods. All major electronic databases were systematically searched from inception until May 2015 using appropriate terms. Studies involving CKD patients with data on circulating MMPs levels and atherosclerosis were considered and subjected to quality assessment. Results. Overall, 16 studies were identified for qualitative synthesis and 9 studies were included in quantitative synthesis. MMP-2 and TIMP-1 were most frequently studied while most studies assessed carotid Intima-Media Thickness (cIMT as a measure of subclinical atherosclerosis. Only MMP-2 demonstrated a consistent positive association with cIMT. Considerable variability in cIMT measurement methodology and poor plaque assessment was found. Conclusions. Although MMPs demonstrate great potential as biomarkers of subclinical atherosclerosis, they are understudied in CKD and not enough data existed for meta-analysis. Larger studies involving several MMPs, with more homogenized approaches in determining the atherosclerotic burden in CKD, are needed.

  11. Association of circulating leukocyte count with coronary atherosclerosis regression after pravastatin treatment.

    Science.gov (United States)

    Tani, Shigemasa; Nagao, Ken; Anazawa, Takeo; Kawamata, Hirofumi; Iida, Kiyoshi; Matsumoto, Michiaki; Sato, Yuichi; Hirayama, Atsushi

    2008-06-01

    Epidemiological studies have demonstrated that the peripheral blood leukocyte count could be used as a marker of the progression of atherosclerosis. Few data exist regarding the relationship between inhibition of the progression of coronary atherosclerosis and the anti-inflammatory effects of statins, especially the drugs' effects on the leukocyte count in patients with coronary artery disease. A 6-month prospective study was, therefore, conducted in 50 patients treated with pravastatin. The plaque volume, as assessed by volumetric analysis using intravascular ultrasound, reduced significantly by 14% (pleukocyte count (8.9%, pleukocyte count and any of the changes in the lipid levels; changes in either of these are known to be associated with the rate of progression of atherosclerosis. A multivariate regression analysis using other traditional risk factors and medications as covariates revealed that the decrease in the leukocyte count was an independent predictor of inhibition of the progression of coronary atherosclerosis. In conclusion, a reduction of the leukocyte count as one of the non-lipid-lowering effects of pravastatin may be a novel marker of regression of coronary atherosclerosis.

  12. Gender-Specific Association of Desacylated Ghrelin with Subclinical Atherosclerosis in the Metabolic Syndrome.

    Science.gov (United States)

    Zanetti, Michela; Gortan Cappellari, Gianluca; Semolic, Annamaria; Burekovic, Ismet; Fonda, Maurizio; Cattin, Luigi; Barazzoni, Rocco

    2017-07-01

    Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). Compared with males, females had higher (p ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the male subgroup. In females, a negative (p ghrelin and AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with cIMT after adjusting for plasma glucose and cardiovascular risk factors. These data indicate a negative independent association between DAG and cIMT in middle-aged women with the MS and suggest a gender-specific modulatory function of DAG in the development of atherosclerosis. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  13. 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

  14. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Cortisol is associated with low frequency of interleukin 10-producing B cells in patients with atherosclerosis.

    Science.gov (United States)

    Huo, Yizhong; Chu, Yan; Guo, Lixin; Liu, Linli; Xia, Xiaojun; Wang, Tierui

    2017-04-01

    It is accepted that inflammation plays a critical role in the development of atherosclerosis; the pathogenesis is not clear. B-cell-produced interleukin (IL) 10 is an immune regulatory cytokine that can inhibit immune inflammation. This study tests a hypothesis that a psychological stress hormone, cortisol, suppresses IL-10 expression in peripheral B cells of patients with atherosclerosis. Peripheral blood samples were collected from patients with coronary artery atherosclerosis. B cells were isolated from the blood samples to be analyzed for the expression of IL-10 and micro RNA (miR) 98 by real-time polymerase chain reaction. We observed that the frequency of IL-10 + B cell was less in patients with atherosclerosis than healthy controls. The serum cortisol levels were higher in the patients than that in healthy controls. Peripheral B-cell frequency was negatively correlated with the serum cortisol levels. Exposure of B cells to cortisol increased the expression of miR-98 in B cells. Cortisol also inhibited the expression of IL-10 in B cells, in which miR-98 played a critical role. Treating B cells from atherosclerosis patients with anti-miR-98 liposomes reversed the ability of expression of IL-10 in the cells. The expression of IL-10 is suppressed in peripheral B cells, which can be up regulated by anti-miR-98 liposomes. Copyright © 2017 John Wiley & Sons, Ltd.

  16. The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Atherosclerosis.

    Science.gov (United States)

    Ivanova, Ekaterina A; Orekhov, Alexander N

    2016-02-01

    Pathogenesis of atherosclerosis is a complex process involving several metabolic and signalling pathways. Accumulating evidence demonstrates that endoplasmic reticulum stress and associated apoptosis can be induced in the pathological conditions of atherosclerotic lesions and contribute to the disease progression. Notably, they may play a role in the development of vulnerable plaques that induce thrombosis and are therefore especially dangerous. Endoplasmic reticulum stress response is regulated by several signaling mechanisms that involve protein kinases and transcription factors. Some of these molecules can be regarded as potential therapeutic targets to improve treatment of atherosclerosis. In this review we will discuss the role of endoplasmic reticulum stress and apoptosis in atherosclerosis development in different cell types and summarize the current knowledge on potential therapeutic agents targeting molecules regulating these pathways and their possible use for anti-atherosclerotic therapy.

  17. Hazard identification of particulate matter on vasomotor dysfunction and progression of atherosclerosis

    DEFF Research Database (Denmark)

    Møller, Peter; Mikkelsen, Lone; Vesterdal, Lise Kristine

    2011-01-01

    and inflammatory pathways. We have assessed the effect of exposure to particulate matter on progression of atherosclerosis and vasomotor function in humans, animals, and ex vivo experimental systems. The type of particles that have been tested in these systems encompass TiO(2), carbon black, fullerene C(60......), single-walled carbon nanotubes, ambient air particles, and diesel exhaust particles. Exposure to ambient air particles is associated with accelerated progression of atherosclerosis and vasomotor dysfunction in both healthy and susceptible animal models and humans at risk of developing cardiovascular...... traditional risk factors for cardiovascular diseases, but superimposed on these and possible exposure to large parts of the population it is a significant public health concern. Overall, assessment of vasomotor dysfunction and progression of atherosclerosis are promising tools for understanding the effects...

  18. Associations between vitamin D status and atherosclerosis among Inuit in Greenland

    DEFF Research Database (Denmark)

    Gjødesen, Camilla U; Jørgensen, Marit E; Bjerregaard, Peter

    2018-01-01

    hypothesized that low vitamin D status could be associated with higher carotid intima-media thickness (IMT) as a marker of atherosclerosis. METHODS: 756 adults from the Inuit Health in Transition (IHIT) study carried out in Greenland in the period 2005-2010 were included. A blood sample donated in 1987...... was available for a sub-sample of 102 individuals. Serum 25(OH)D3 from the IHIT study and the 1987 survey was used as a measure of vitamin D status. IMT measurements were conducted by ultrasound scanning. The prevalence of atherosclerosis was estimated, and the association between serum 25(OH)D3 and IMT...... measurements was examined by linear regression. RESULTS: The overall prevalence of subclinical atherosclerosis was 20.1% (n = 152). The linear regression analyses indicated a weak positive association between serum 25(OH)D3 level and IMT measurements from the IHIT study, though not statistically significant...

  19. Resistin may be an independent predictor of subclinical atherosclerosis formale smokers.

    Science.gov (United States)

    He, Ying; Bai, Xiao-Jun; Li, Fen-Xia; Fan, Li-Hong; Ren, Jie; Liang, Qi; Li, Hong-Bing; Bai, Ling; Tian, Hong-Yan; Fan, Fen-Ling; Tian, Gang; Ma, Ai-Qun; Chen, Jinghong

    To investigate whether resistin is associated with early atherosclerosis in male smokers. The present study consecutively enrolled 50 male smokers. Their serum resistin contents were detected with enzyme linked immunosorbent assay (ELISA), and subclinical atherosclerosis indices, including carotid inner middle thickness (IMT) and arterial elasticity indices (C1 and C2), were measured. The association between serum resistin levels and IMT, C1 and C2 were respectively evaluated with the Pearson's correlation coefficient method. The results showed that the serum resistin level had a positive association with IMT (r = 0.307, p = .030), but were both inversely associated with C1 (r = -0.440, p = .001) and C2 (r = -0.381, p = .006). These associations remained significant even after adjustment for cardiovascular confounders. In conclusion, serum resistin concentration was independently associated with early atherosclerosis in male smokers.

  20. 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...... unsupplemented group). Atherosclerosis was significantly less in the fish oil group compared with the corn oil group when evaluated en face in the aortic arch (area positive to lipid staining: 32% with fish oil versus 38% with corn oil; 48% with unsupplemented diet). Conclusions: n-3 and n-6 PUFA supplementation...

  1. Senescent intimal foam cells are deleterious at all stages of atherosclerosis.

    Science.gov (United States)

    Childs, Bennett G; Baker, Darren J; Wijshake, Tobias; Conover, Cheryl A; Campisi, Judith; van Deursen, Jan M

    2016-10-28

    Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr-/-) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. Together, these results demonstrate that senescent cells are key drivers of atheroma formation and maturation and suggest that selective clearance of these cells by senolytic agents holds promise for the treatment of atherosclerosis. Copyright © 2016, American Association for the Advancement of Science.

  2. Atherosclerosis subclinical and inflammatory markers in obese and nonobese children and adolescents.

    Science.gov (United States)

    Silva, Larissa R; Stefanello, Joice M F; Pizzi, Juliana; Timossi, Luciana S; Leite, Neiva

    2012-12-01

    We conducted a systematic review of intima-media thickness(IMT) and inflammatory markers, compared IMT and identified by meta-analysis related to EMI and inflammatory variables in obese and non-obese children and adolescents. We searched for articles in databases Pubmed, Bireme and Science Direct, during years 2000 to 2010, with the following key words in English: "obesity", "adolescents", "atherosclerosis" and "child ", They were used in two combinations: obesity + adolescents + atherosclerosis + child + obesity and atherosclerosis. We used meta-analysis to compare IMT between obese and non-obese patients. We carefully selected 16 articles for final analysis. There were differences in the thickness of IMT between obese and non-obese patients in 12 studies, confirmed by meta-analysis. Obese patients had concentrations of C-reactive protein higher in 13 articles analyzed (p markers in this phase.

  3. DNA Damage and Repair in Atherosclerosis: Current Insights and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Maria Grazia Andreassi

    2012-12-01

    Full Text Available Atherosclerosis is the leading cause of morbidity and mortality among Western populations. Over the past two decades, considerable evidence has supported a crucial role for DNA damage in the development and progression of atherosclerosis. These findings support the concept that the prolonged exposure to risk factors (e.g., dyslipidemia, smoking and diabetes mellitus leading to reactive oxygen species are major stimuli for DNA damage within the plaque. Genomic instability at the cellular level can directly affect vascular function, leading to cell cycle arrest, apoptosis and premature vascular senescence. The purpose of this paper is to review current knowledge on the role of DNA damage and DNA repair systems in atherosclerosis, as well as to discuss the cellular response to DNA damage in order to shed light on possible strategies for prevention and treatment.

  4. Premature atherosclerosis in a Japanese diabetic patient with atypical familial partial lipodystrophy and hypertriglyceridemia.

    Science.gov (United States)

    Iwanishi, Masanori; Ebihara, Ken; Kusakabe, Toru; Harada, Shinji; Ito-Kobayashi, Jun; Tsuji, Atsushi; Hosoda, Kiminori; Nakao, Kazuwa

    2012-01-01

    We herein report a case of premature atherosclerosis in a patient with familial partial lipodystrophy (FPL), diabetes mellitus, hypertension and hypertriglyceridemia. Sequencing of the candidate genes LMNA, PPARG and CAV1 associated with FPL revealed no genetic abnormalities, which indicated the activity of a novel gene in this patient. The patient's son showed milder fat loss and similar fat distribution compared to the proband; however, the son showed no signs of any atherosclerotic disease. Although a cluster of atherogenic risk factors is likely to be the primary causes of atherosclerosis in our patient, other factors, including an unknown gene associated with FPL, the severity of fat loss and gender, might affect the development of atherosclerosis.

  5. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis.

    Science.gov (United States)

    Alexopoulos, Nikolaos; Katritsis, Demosthenes; Raggi, Paolo

    2014-03-01

    The current epidemic of obesity with the associated increasing incidence of insulin resistance, diabetes mellitus and atherosclerosis affecting a large proportion of the North American and Western populations, has generated a strong interest in the potential role of visceral adipose tissue in the development of atherosclerosis and its complications. The intra-abdominal and epicardial space are two compartments that contain visceral adipose tissue with a similar embryological origin. These visceral fats are highly inflamed in obese patients, patients with the metabolic syndrome and in those with established coronary artery disease; additionally they are capable of secreting large quantities of pro-inflammatory cytokines and free fatty acids. There is accumulating evidence to support a direct involvement of these regional adipose tissue deposits in the development of atherosclerosis and its complicating events, as will be reviewed in this article. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Progress and future opportunities in the development of vaccines against atherosclerosis.

    Science.gov (United States)

    Govea-Alonso, Dania O; Beltrán-López, Josué; Salazar-González, Jorge A; Vargas-Morales, Juan; Rosales-Mendoza, Sergio

    2017-04-01

    Atherosclerosis represents a serious global health problem that demands new therapeutic and prophylactic interventions. Considering that atherosclerosis has autoimmune and inflammatory components, immunotherapy is a possible focus to treat this disease. Areas covered: Based on the analysis of the current biomedical literature, this review describes the status on the development of vaccines against atherosclerosis. Several targets have been identified including sequences of apolipoprotein B100 (ApoB100), cholesteryl ester transfer protein (CETP), heat shock proteins (HSP), extracellular matrix proteins, T cell receptor β chain variable region 31 (TRBV31), the major outer membrane protein (MOMP), and the outer membrane protein 5 (Pomp5) from Chlamydia pneumoniae. Humoral and cellular immunities to these targets have been associated with therapeutic effects in murine models and humans. The evaluation of some candidates in clinical trials is ongoing. Expert commentary: New research paths based on the use of next generation vaccine production platforms are envisioned.

  7. 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..., including the use of appropriate automated, electronic, mechanical, or other technological collection...

  8. Multivariate statistical evaluation of trace metal levels in the blood of atherosclerosis patients in comparison with healthy subjects

    Directory of Open Access Journals (Sweden)

    Asim Ilyas

    2016-01-01

    Conclusion: Overall, the distribution, correlation and multivariate apportionment of selected metals in atherosclerosis patients and healthy donors are significantly divergent. Hence, present findings suggest that the trace and redox metals accumulated in the body may pose a high risk for atherosclerosis development.

  9. Microvascular endothelial dysfunction predicts the development of erectile dysfunction in men with coronary atherosclerosis without critical stenoses

    OpenAIRE

    Reriani, M; Flammer, A. J.; Li, J; M. Prasad; Rihal, C; Prasad, A.; Lennon, R; Lerman, L.O.; Lerman, A

    2014-01-01

    BACKGROUND: Erectile dysfunction (ED) is associated with an increased risk for cardiovascular disease, stroke, and all-cause mortality, independent of conventional cardiovascular risk factors. Coronary endothelial dysfunction is independently associated with ED in men with early coronary atherosclerosis. We aimed to investigate whether coronary microvascular dysfunction predicts development of ED in patients presenting with coronary atherosclerosis without critical stenoses. PATIENTS AND METH...

  10. Design and development of nanomedicines to treat atherosclerosis: A cross platform head-to-head theranostic study

    NARCIS (Netherlands)

    Alaarg, Amr|info:eu-repo/dai/nl/370549465; Perez Medina, Carlos; Tang, Jun; Fay, Francois; Zhao, Yiming|info:eu-repo/dai/nl/355358352; Sanchez-Gaytan, Brenda; Reiner, Thomas; Fayad, Zahi A.; Kok, Robbert J.|info:eu-repo/dai/nl/170678326; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Mulder, Willem J.; Storm, G|info:eu-repo/dai/nl/073356328

    2016-01-01

    Background: Atherosclerosis is a chronic inflammatory disease of the large arteries and a leading cause of death worldwide. Macrophages are key players in the progression of atherosclerosis and are a compelling target for disease management [1]. Statins, HMG-CoA reductase inhibitors, exhibit

  11. Association of Mild-to-Moderate Reduction in Glomerular Filtration Rate with Subclinical Atherosclerosis in Postmenopausal Women.

    Science.gov (United States)

    Parv, Florina; Beceanu, Andrei; Avram, Rodica; Timar, Romulus Zorin; Timar, Bogdan; Gadalean, Florica

    2017-05-24

    Due to loss of hormonal protective effects, postmenopausal women have an increased cardiovascular (CV) risk. Chronic kidney disease (CKD) is a well-established risk factor for CV disease, but little is known whether mild-to-moderate kidney dysfunction is associated with atherosclerosis burden in the postmenopausal asymptomatic women. Subclinical atherosclerosis was evaluated in 125 postmenopausal women with no clinical form of atherosclerosis, by carotid and femoral ultrasonography, ankle-brachial index (ABI), and flow-mediated dilation (FMD). Carotid and femoral atherosclerosis were defined as increased intima-media thickness (IMT) and/or the presence of plaques. Endothelial function was assessed by endothelial dependent (flow-mediated dilation at 1 minute [FMD1]) and independent (flow-mediated dilation after nitroglycerin [FMDNTG]) vasodilation. Classical CV risk factors (age, smoking, obesity, diabetes, blood pressure, and lipids) were evaluated. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Univariate linear regression and multivariate logistic regressions were used to evaluate the independent associations between kidney function and markers of subclinical atherosclerosis. In the unadjusted linear analysis, eGFR showed a significant negative association with markers of subclinical atherosclerosis: carotid IMT (R(2) = 0.305; p subclinical atherosclerosis, independent of traditional CV risk factors. It is important to detect renal function decline, even if it is mild, to improve risk stratification of subclinical atherosclerosis in postmenopausal women.

  12. 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

  13. 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....

  14. Prevalence of coronary atherosclerosis in asymptomatic healthy subjects: an intravascular ultrasound study of donor hearts.

    Science.gov (United States)

    Kim, Min-Seok; Kang, Soo-Jin; Lee, Cheol-Whan; Han, Seungbong; Park, Duk-Woo; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Park, Seung-Jung; Kim, Jae-Joong

    2013-01-01

    At present, limited in vivo information is available on the prevalence and severity of coronary atherosclerosis in asymptomatic healthy subjects. The aim of this study was to examine the prevalence, extent and severity of coronary atherosclerosis in healthy individuals. We performed an intravascular ultrasound (IVUS) examination on 198 heart transplant recipients 4 weeks after transplantation. The donor population consisted of 147 men and 51 women (31.4±11.0 years). The left anterior descending coronary artery was imaged in all patients, and 3 vessel images were obtained for 99 patients. Angiographic appearance was completely normal in 177 of the 198 subjects (89.4%), while atherosclerotic luminal irregularities were observed in the remaining individuals. IVUS revealed that atherosclerotic lesions (defined as intimal thickness ≥0.5 mm at any site) were present in 96 patients (48.5%). The prevalence of coronary atherosclerosis rapidly increased with age (10-19 years, 5.9%; 20-29 years, 31.1%; 30-39 years, 59.0%; 40-49 years, 78.4%). In the diseased subgroup, atherosclerotic lesions were mostly eccentric (92.7%), with maximal intimal thickness of 0.99±0.42 mm (area stenosis, 32.2±11.7%). All coronary arteries were predominantly located in the proximal third of each vessel. Donor age, male sex, and hypertension were the determinants of coronary atherosclerosis measured by IVUS examination. As more risk factors were present, the risk of atherosclerosis increased. Coronary atherosclerosis is common in asymptomatic young healthy adults, supporting the need for preventive cardiology in the early stages of life.

  15. Screening for subclinical atherosclerosis by noninvasive methods in asymptomatic patients with risk factors

    Directory of Open Access Journals (Sweden)

    Castellon X

    2013-05-01

    Full Text Available Xavier Castellon, Vera BogdanovaDepartment of Cardiology, Private Hospital Athis Mons, Paris, FranceAbstract: Atherosclerosis is a leading cause of cardiovascular death due to the increasing prevalence of the disease and the impact of risk factors such as diabetes, obesity or smoking. Sudden cardiac death is the primary consequence of coronary artery disease in 50% of men and 64% of women. Currently the only available strategy to reduce mortality in the at-risk population is primary prevention; the target population must receive screening for atherosclerosis. The value of screening for subclinical atherosclerosis is still relevant, it has become standard clinical practice with the emergence of new noninvasive techniques (radio frequency [RF] measurement of intima-media thickness [RFQIMT] and arterial stiffness [RFQAS], and flow-mediated vasodilatation [FMV], which have been used by our team since 2007 and are based on detection marker integrators which reflect the deleterious effect of risk factors on arterial remodeling before the onset of clinical events. These techniques allow the study of values according to age and diagnosis of the pathological value, the thickness of the intima media (RFQIMT, the speed of the pulse wave (RFQAS, and the degree of endothelial dysfunction (FMV. This screening is justified in asymptomatic patients with cardiovascular risk factors (hypertension, diabetes, obesity, dyslipidemia, and tobacco smoking. Studies conducted by RF coupled with two-dimensional echo since 2007 have led to a more detailed analysis of the state of the arterial wall. The various examinations allow an assessment of the degree of subclinical atherosclerosis and its impact on arterial remodeling and endothelial function. The use of noninvasive imaging in screening and early detection of subclinical atherosclerosis is reliable and reproducible and allows us to assess the susceptibility of our patients with risk factors and ensures better

  16. A rabbit model of atherosclerosis at carotid artery: MRI visualization and histopathological characterization

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zhan-Long; Teng, Gao-Jun; Chen, Jun; Zhang, Hong-Ying; Cao, Ai-Hong [Zhong-Da Hospital, Southeast University, Molecular Imaging Laboratory, Department of Radiology, Nanjing (China); Ni, Yicheng [University Hospitals, Catholic University of Leuven, Department of Radiology, Leuven (Belgium)

    2008-10-15

    To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T{sub 1}-weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis. (orig.)

  17. Relationship of Hypertension to Coronary Atherosclerosis and Cardiac Events in Patients With Coronary Computed Tomographic Angiography.

    Science.gov (United States)

    Nakanishi, Rine; Baskaran, Lohendran; Gransar, Heidi; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Cury, Ricardo; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Kaufmann, Philipp A; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Pontone, Gianluca; Andreini, Daniele; Rubinshtein, Ronen; Bax, Jeroen; Jones, Erica; Hindoyan, Niree; Gomez, Millie; Lin, Fay Y; Min, James K; Berman, Daniel S

    2017-08-01

    Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events. © 2017 American Heart Association, Inc.

  18. The "Mevalonate hypothesis": a cholesterol-independent alternative for the etiology of atherosclerosis.

    Science.gov (United States)

    Keizer, Hiskias G

    2012-11-05

    The "cholesterol hypothesis" is the leading theory to explain the cause of atherosclerosis. The "cholesterol hypothesis" assumes that plasma (LDL) cholesterol is an important causal factor for atherosclerosis.However, data of at least seven placebo controlled randomized prospective trials with various cholesterol lowering drugs show that plasma cholesterol lowering does not necessarily lead to protection against cardiovascular disease. Therefore an alternative hypothesis for the etiology of cardiovascular disease is formulated. This alternative hypothesis, the "mevalonate hypothesis", assumes that after stimulation of the mevalonate pathway in endothelial cells by inflammatory factors, these cells start producing cholesterol and free radicals. In this hypothesis, only the latter play a role in the etiology of atherosclerosis by contributing to the formation of oxidized cholesterol which is a widely accepted causal factor for atherosclerosis.Regardless of how the mevalonate pathway is activated (by withdrawal of statin drugs, by inflammatory factors or indirectly by reduced intracellular cholesterol levels) in all these cases free radical production is observed as well as cardiovascular disease. Since in the "mevalonate hypothesis" cholesterol is produced at the same time as the free radicals causing atherosclerosis, this hypothesis provides an explanation for the correlation which exists between cardiovascular disease and plasma cholesterol levels. From an evolutionary perspective, concomitant cholesterol production and free radical production in response to inflammatory factors makes sense if one realizes that both activities potentially protect cells and organisms from infection by gram-negative bacteria.In conclusion, data have been collected which suggest that activation of the mevalonate pathway in endothelial cells is likely to be a causal factor for atherosclerosis. This "mevalonate hypothesis" provides a better explanation for results obtained from recent

  19. Elevated circulating sST2 associated with subclinical atherosclerosis in newly diagnosed primary hypertension.

    Science.gov (United States)

    Ates, Ihsan; Ozkayar, Nihal; Ates, Hale; Karakulak, Uğur Nadir; Kursun, Oğuzhan; Topcuoglu, Canan; Inan, Bayram; Yilmaz, Nisbet

    2016-07-01

    The aims of this study were to measure the levels of interleukin-33 (IL-33) and soluble Suppression of Tumorigenicity 2 (sST2) in patients with newly diagnosed primary hypertension (HT) and to determine the relationship between carotid intima-media thickness (CIMT) and IL-33/sST2. Eighty-two patients with newly diagnosed primary HT and ninety healthy volunteers were included in the study. CIMT ⩾0.9 mm was considered as significant for subclinical atherosclerosis. The sST2 levels of patients with primary HT were higher than those of the control group, whereas the IL-33 levels of these patients were much lower than those of the control group. The sST2 levels were higher in patients with subclinical atherosclerosis than in control subjects or patients with primary HT but not with subclinical atherosclerosis. In the primary HT group, sST2 had a positive correlation with CIMT, 24-h systolic-diastolic blood pressure, low-density lipoprotein and C-reactive protein, whereas sST2 had a negative correlation with the IL-33 level. A stepwise multivariable logistic regression analysis revealed that sST2 is an independent risk factor for subclinical atherosclerosis. Although the diagnostic predictive value of HT risk was determined as >51.8 pg l(-1) in the receiver operating characteristic curve analysis in respect of the sST2 level, the diagnostic predictive value for subclinical atherosclerosis risk was determined to be >107.2 pg l(-1). The sST2 level displays a positive correlation with atherosclerotic changes, and is an independent risk factor for subclinical atherosclerosis expressed as increased CIMT.

  20. Signature of subclinical femoral artery atherosclerosis in peripheral blood mononuclear cells.

    Science.gov (United States)

    Llorente-Cortés, Vicenta; de Gonzalo-Calvo, David; Orbe, Josune; Páramo, Jose Antonio; Badimon, Lina

    2014-06-01

    Peripheral arterial disease is a relevant public health problem associated with increased risk of morbimortality. Most of the patients with this condition are asymptomatic. Therefore, the development of accessible biochemical markers seems to be necessary to anticipate diagnosis. Our hypothesis is that asymptomatic subjects with objectively confirmed femoral artery atherosclerosis could be distinguished from control subjects by gene expression analysis in peripheral blood mononuclear cells (PBMC). A total of 37 asymptomatic males over 50 years old were recruited at the University Clinic of Navarra (Spain). Nineteen participants were free from atherosclerotic vascular disease and 18 participants presented subclinical femoral artery atherosclerosis defined by means of Doppler ultrasound. PBMC were isolated from blood and the RNA extracted. A panel of atherosclerotic-related genes were evaluated by Taqman low-density array. In univariate logistic regression models, we found a direct relationship between IL4, ITGAM and TLR2 expression levels in PBMC and femoral atherosclerosis, even when the models were adjusted for age and hypertension prevalence. Multivariate logistic regression models showed that elevated IL4 expression levels were intimately associated with subclinical femoral atherosclerosis after adjusting for the same potential confounders. Current data suggest that gene expression in PBMC, in particular IL4 expression, could be a useful tool in the diagnosis of femoral artery atherosclerosis in asymptomatic patients. Furthermore, in patients with no differences in cardiovascular risk factors except for hypertension, the results point to the immune and inflammatory deregulation as a feature of subclinical peripheral atherosclerosis. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  1. Multiparametric assessment of vascular function and atherosclerosis in patients with autoimmune gastritis: a comparative study.

    Science.gov (United States)

    Yakut, Mustafa; Ustün, Yusuf; Kutlay, Sim; Ongun, Aydan; Kabaçam, Gökhan; Boynueğri, Recai; Soykan, Irfan

    2011-12-01

    Patients with autoimmune gastritis might have accelerated atherosclerosis due to autoimmunity and chronic inflammation. Endothelial dysfunction often precedes manifest atherosclerosis. The aim of the present study was to evaluate the risk factors of early atherosclerosis by using several different techniques. A total of 99 patients with autoimmune gastritis were compared to 42 healthy age sex-matched subjects. Patients with a known risk factor for atherosclerosis were excluded. Intima-media thickness of the common carotid artery, pulse wave velocity and flow-mediated dilation of brachial artery were measured. Clinical data and laboratory parameters (serum gastrin, antiparietal cell antibody, anti-Hp IgG, serum vitamin B(12) and lipid profile) were also determined. Intima-media thickness (mm) of the carotid artery was significantly higher in autoimmune gastritis (0.062 ± 0.031 vs. 0.042 ± 0.007, P gastritis compared to control group (13.91 ± 6.68% vs. 20.37 ± 7.80%, P = 0.021) and there was a significant increase in pulse wave velocity (m/s) in autoimmune gastritis patients compared to controls (9.25 ± 3.42 vs. 6.40 ± 0.91, P = 0.001). Antiparietal cell antibody positivity (P = 0.05), low vitamin B(12) level (P = 0.05), and age (P = 0.002) were the predictors of high pulse wave velocity (>14 m/s). Patients with autoimmune gastritis may have an increased risk for the development of early atherosclerosis. As early preventive treatment for accelerated atherosclerosis is available, it is important to detect those patients with autoimmune gastritis who would benefit from such treatment.

  2. 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

  3. Genetic deletion of platelet glycoprotein Ib alpha but not its extracellular domain protects from atherosclerosis.

    Science.gov (United States)

    Koltsova, E K; Sundd, P; Zarpellon, A; Ouyang, H; Mikulski, Z; Zampolli, A; Ruggeri, Z M; Ley, K

    2014-12-01

    The pathogenesis of atherosclerosis involves the interplay of haematopoietic, stromal and endothelial cells. Platelet interactions with endothelium and leukocytes are pivotal for atherosclerosis promotion. Glycoprotein (GP) Ibα is the ligand-binding subunit of the platelet GPIb-IX-V receptor complex; its deficiency causes the Bernard-Soulier syndrome (BSS), characterised by absent platelet GPIb-IX-V, macrothrombocytopenia and bleeding. We designed this study to determine the role of platelet GPIbα in the pathogenesis of atherosclerosis using two unique knockout models. Ldlr-/- mice were reconstituted with wild-type (wt), GPIbα-/- (lacks GPIbα) or chimeric IL-4R/GPIbα-Tg (lacks GPIbα extracellular domain) bone marrow and assayed for atherosclerosis development after feeding with pro-atherogenic "western diet". Here, we report that Ldlr-/-mice reconstituted with GPIbα-/- bone marrow developed less atherosclerosis compared to wt controls; accompanied by augmented accumulation of pro-inflammatory CD11b+ and CD11c+ myeloid cells, reduced oxLDL uptake and decreased TNF and IL 12p35 gene expression in the aortas. Flow cytometry and live cell imaging in whole blood-perfused microfluidic chambers revealed reduced platelet-monocyte aggregates in GPIbα-/- mice, which resulted in decreased monocyte activation. Interestingly, Ldlr-/-mice reconstituted with IL-4R/GPIbα-Tg bone marrow, producing less abnormal platelets, showed atherosclerotic lesions similar to wt mice. Platelet interaction with blood monocytes and accumulation of myeloid cells in the aortas were also essentially unaltered. Moreover, only complete GPIbα ablation altered platelet microparticles and CCL5 chemokine production. Thus, atherosclerosis reduction in mice lacking GPIbα may not result from the defective GPIbα-ligand binding, but more likely is a consequence of functional defects of GPIbα-/- platelets and reduced blood platelet counts.

  4. Association of Serum Vitamin D Level and Carotid Atherosclerosis: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Chen, Fu-Hua; Liu, Tian; Xu, Lei; Zhang, Lei; Zhou, Xiao-Bo

    2017-11-24

    Vitamin D deficiency is associated with an increased risk of subclinical atherosclerosis. To explore the potential link of the serum vitamin D level with carotid atherosclerosis, this meta-analysis assessed the correlation between vitamin D and carotid intima-media thickness as well as carotid atherosclerotic plaque. PubMed, Embase, Web of Science, and Cochrane Library databases were searched until the end of March 2017. Clinical studies investigating the relationship between vitamin D and carotid atherosclerosis were included. The outcome data were extracted according to the inclusion criteria and pooled for an effect estimate by a random-effects model. Of the 506 initially retrieved studies, 11 studies involving a total of 16,434 participants were included in the meta-analysis. Newcastle-Ottawa Quality Assessment Scale scores suggested that the included studies were of high quality. The pooled effects estimate showed that the serum vitamin D level was negatively associated with carotid atherosclerosis (odds ratio, 0.95; 95% confidence interval [CI], 0.93-0.96), with substantial heterogeneity among the individual studies (I2  = 54%). Furthermore, a subgroup analysis suggested that hypovitaminosis D was associated with an 0.85-fold decrease in the odds of having a higher carotid intima-media thickness (95% CI, 0.76-0.96; P D level was a protective factor against increased carotid plaque (odds ratio, 0.95; 95% CI, 0.93-0.97; P D deficiency and carotid atherosclerosis. Patients with hypovitaminosis D might have extra requirements for preventive and therapeutic measures against early atherosclerosis, thus reducing the cardiovascular disease risk in the long term. © 2017 by the American Institute of Ultrasound in Medicine.

  5. FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells

    Science.gov (United States)

    Zhu, Min; Zhang, Qing-Jun; Wang, Lin; Li, Hao; Liu, Zhi-Ping

    2011-01-01

    Objectives FoxO proteins are transcription factors involved in varieties of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. Although these processes are implicated in the development of atherosclerosis, very little is known about the role of FoxO proteins in the context of atherosclerosis. Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis. Methods and Results Apolipoprotein E-deficient (apoE−/−) mice were crossbred with animals lacking Foxo4 (Foxo4−/−). After 10 weeks on a high fat diet (HFD), Foxo4−/−apoE−/− mice showed elevated atherosclerosis and increased amount of macrophages and T cells in the plaque compared to apoE−/− mice. Bone marrow transplantations of chimeric C57B/6 mice reconstituted with either wild-type or Foxo4−/− bone marrows indicate that Foxo4-deficiency in bone marrow derived cells sufficiently promoted atherosclerosis. Foxo4-null macrophages produced elevated inflammatory cytokine IL-6 and levels of reactive oxygen species (ROS) in response to lipopolysaccharides in vitro. Serum levels of IL-6 were upregulated in HFD-fed Foxo4−/−apoE−/− mice compared to those of apoE−/− mice. Conclusions FoxO4 inhibits atherosclerosis through bone marrow derived cells, possibly by inhibition of ROS and inflammatory cytokines that promote monocyte recruitment and/or retention. PMID:22005198

  6. ARFI imaging for noninvasive material characterization of atherosclerosis. Part II: toward in vivo characterization.

    Science.gov (United States)

    Behler, Russell H; Nichols, Timothy C; Zhu, Hongtu; Merricks, Elizabeth P; Gallippi, Caterina M

    2009-02-01

    Seventy percent of cardiovascular disease (CVD) deaths are attributed to atherosclerosis. Despite their clinical significance, nonstenotic atherosclerotic plaques are not effectively detected by conventional atherosclerosis imaging methods. Moreover, conventional imaging methods are insufficient for describing plaque composition, which is relevant to cardiovascular risk assessment. Atherosclerosis imaging technologies capable of improving plaque detection and stratifying cardiovascular risk are needed. Acoustic radiation force impulse (ARFI) ultrasound, a novel imaging method for noninvasively differentiating the mechanical properties of tissue, is demonstrated for in vivo detection of nonstenotic plaques and plaque material assessment in this pilot investigation. In vivo ARFI imaging was performed on four iliac arteries: (1) of a normocholesterolemic pig with no atherosclerosis as a control, (2) of a familial hypercholesterolemic pig with diffuse atherosclerosis, (3) of a normocholesterolemic pig fed a high-fat diet with early atherosclerotic plaques and (4) of a familial hypercholesterolemic pig with diffuse atherosclerosis and a small, minimally occlusive plaque. ARFI results were compared with spatially matched immunohistochemistry, showing correlations between elastin and collagen content and ARFI-derived peak displacement and recovery time parameters. Faster recoveries from ARFI-induced peak displacements and smaller peak displacements were observed in areas of higher elastin and collagen content. Importantly, spatial correlations between tissue content and ARFI results were consistent and observable in large and highly evolved as well as small plaques. ARFI imaging successfully distinguished nonstenotic plaques, while conventional B-mode ultrasound did not. This work validates the potential relevance of ARFI imaging as a noninvasive imaging technology for in vivo detection and material assessment of atherosclerotic plaques.

  7. The “Mevalonate hypothesis”: a cholesterol-independent alternative for the etiology of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Keizer Hiskias G

    2012-11-01

    Full Text Available Abstract The “cholesterol hypothesis” is the leading theory to explain the cause of atherosclerosis. The “cholesterol hypothesis” assumes that plasma (LDL cholesterol is an important causal factor for atherosclerosis. However, data of at least seven placebo controlled randomized prospective trials with various cholesterol lowering drugs show that plasma cholesterol lowering does not necessarily lead to protection against cardiovascular disease. Therefore an alternative hypothesis for the etiology of cardiovascular disease is formulated. This alternative hypothesis, the “mevalonate hypothesis”, assumes that after stimulation of the mevalonate pathway in endothelial cells by inflammatory factors, these cells start producing cholesterol and free radicals. In this hypothesis, only the latter play a role in the etiology of atherosclerosis by contributing to the formation of oxidized cholesterol which is a widely accepted causal factor for atherosclerosis. Regardless of how the mevalonate pathway is activated (by withdrawal of statin drugs, by inflammatory factors or indirectly by reduced intracellular cholesterol levels in all these cases free radical production is observed as well as cardiovascular disease. Since in the “mevalonate hypothesis” cholesterol is produced at the same time as the free radicals causing atherosclerosis, this hypothesis provides an explanation for the correlation which exists between cardiovascular disease and plasma cholesterol levels. From an evolutionary perspective, concomitant cholesterol production and free radical production in response to inflammatory factors makes sense if one realizes that both activities potentially protect cells and organisms from infection by gram-negative bacteria. In conclusion, data have been collected which suggest that activation of the mevalonate pathway in endothelial cells is likely to be a causal factor for atherosclerosis. This “mevalonate hypothesis” provides a

  8. The regulator of calcineurin (RCAN1) an important factor involved in atherosclerosis and cardiovascular diseases development.

    Science.gov (United States)

    Torac, E; Gaman, L; Atanasiu, V

    2014-01-01

    Atherosclerosis, one of the main causes of cardiovascular diseases, is a complex process that involves manifold factors. Besides the vascular lipids accumulation, inflammatory factors could be considered as a proatherogenic factor - RCAN1. RCAN1 is a regulator of calcineurin, both of them being calcium dependent proteins. Recent studies have shown that RCAN1 has an important role in heart valve development. In the same time researchers found that, the atherosclerotic plaques have an up-regulated RCAN1 gene expression. In the near future, it is desirable to elucidate the RCAN1 function and classify it as a possible biochemical marker to diagnose infancy atherosclerosis.

  9. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

    OpenAIRE

    Fontana, Luigi; Meyer, Timothy E.; Klein, Samuel; Holloszy, John O.

    2004-01-01

    Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reac...

  10. 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

    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......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...

  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. Association Between a Social-Business Eating Pattern and Early Asymptomatic Atherosclerosis.

    Science.gov (United States)

    Peñalvo, José L; Fernández-Friera, Leticia; López-Melgar, Beatriz; Uzhova, Irina; Oliva, Belén; Fernández-Alvira, Juan Miguel; Laclaustra, Martín; Pocock, Stuart; Mocoroa, Agustín; Mendiguren, José M; Sanz, Ginés; Guallar, Eliseo; Bansilal, Sameer; Vedanthan, Rajesh; Jiménez-Borreguero, Luis Jesús; Ibañez, Borja; Ordovás, José M; Fernández-Ortiz, Antonio; Bueno, Héctor; Fuster, Valentin

    2016-08-23

    The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. This study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults. The PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style-related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information. Most PESA participants follow a Mediterranean (40% of participants) or a Western (41%) dietary pattern. A new pattern, identified among 19% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet. A new social-business eating pattern, characterized by high consumption of red and processed meat, alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy

  13. The Quality of Life in Patients with Ulcerative Colitis and Concomitant Subclinical Atherosclerosis

    Directory of Open Access Journals (Sweden)

    I.V. Chopei

    2015-06-01

    In patients with UC and concomitant atherosclerosis we have detected deterioration in quality of life mostly by the components of physical health (SF-36 questionnaire, which is directly proportional to the degree of atherosclerosis severity (p < 0.05. During combined treatment with statins and omega-3 PUFAs, there was a significant improvement in parameters of not only physical, but also mental health (p < 0.05. Analyzing data by specialized GSRS questionnaires, we have noted improvement in quality of life by three of the five scales — abdominal pain, dyspeptic and diarrheal syndromes (p < 0.05.

  14. Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Barascuk, Natasha; Register, Thomas

    2010-01-01

    in almost all stages of atherosclerosis, by both initiating atherosclerotic plaques and degrading them through the secretion of proteolytic enzymes leading to rupture. This review summarizes the literature on the role of macrophages and their proteolytic activity on proteins in the extracellular matrix (ECM......) of the atherosclerotic plaque with a view to suggest a novel approach for identification of vulnerable plaques and turnover by the use of a new type of biomarker. The PubMed database was searched using the terms macrophages, foam cells, atherosclerosis, CVD, ECM remodeling, biomarker, neoepitope, matrix...

  15. Linking Immunity to Atherosclerosis: Implications for Vascular Pharmacology - A tribute to Göran K. Hansson

    Science.gov (United States)

    Geng, Yong-Jian; Jonasson, Lena

    2011-01-01

    For the past decade, we have deepened our understanding of the pathogenesis of atherosclerosis, a chronic arterial disease that causes cardiac and cerebral infarction and peripheral vascular disorders. Because of this extended understanding, more effective strategies for prevention and treatment of this disease are emerging. One of the fundamental mechanisms that lead to progress or regression in atherosclerosis, thus influencing its life-threatening complications, occurs through functional changes in vascular immunity and inflammation. This review briefly summarized the discoveries in basic and translational sciences in this area and recent advances in clinical medicine against atherosclerotic vascular diseases. PMID:22120836

  16. Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis

    DEFF Research Database (Denmark)

    Pedersen, Annemarie Aarup; Pedersen, Tanja X; Junker, Nanna

    2016-01-01

    transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr(-/-) recipient mice by ≈72% (P=0.006).In vitro, HIF-1α-deficient macrophages displayed decreased differentiation...... to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages. CONCLUSIONS: HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis....

  17. Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies

    DEFF Research Database (Denmark)

    Thim, Troels; Hagensen, Mette; Drouet, L.

    2010-01-01

    AIMS: A manageable and reproducible large animal model of human-like coronary atherosclerosis is lacking but highly needed for translational research in percutaneous coronary interventions and imaging. Farm pigs with familial hypercholesterolaemia develop advanced atherosclerosis in two to three...... years but then weigh >200 kg making them impractical and costly. We aimed at down-sizing this pig and accelerating coronary plaque development to make the model more useful and affordable. METHODS AND RESULTS: Familial hypercholesterolaemic farm pigs were downsized by crossing them with smaller pigs...

  18. 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.

  19. Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects.

    Science.gov (United States)

    Parrinello, G; Colomba, D; Bologna, P; Licata, A; Pinto, A; Paterna, S; Scaglione, R; Licata, G

    2004-03-01

    Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO/ISH criteria), were selected from a database consisting of 3541 subjects referred to ultrasound cardiovascular laboratory in the last 5 years. Carotid intima-media thickness (IMT) was detected by high-resolution vascular ultrasound and left ventricular structure and function by the use of Doppler echocardiography. According to carotid IMT values, all patients were subgrouped into two groups consisting of 89 (62.6%) pts with IMT > or = 1 mm (A) and 53 (37.4%) pts with IMT < 1 mm (B). Our results show that isovolumic relaxation time (IVRT), deceleration time of E velocity (EDT) and left ventricular relative wall thickness (LV-RWT) were significantly (P < 0.05) higher in group A (IVRT 112 +/- 8.9 ms; EDT 288 +/- 21.8 ms; LV-RWT 0.40 +/- 0.08) than in group B (IVRT 92.3 +/- 4.6 ms; EDT 203.3 +/- 27.01 ms; LV- RWT 0.37 +/- 0.06). Moreover, the prevalence of left ventricular hypertrophy (LVH) was significantly (P < 0.01) higher in group A (30/89; 33.7%) than in group B (8/53; 15%). A positive correlation (P < 0.001) between IMT, EDT and IVRT was found only in hypertensives without LVH. These results are consistent with the indication that IMT evaluation has to be recommended both in hypertensive patients with LVH and in those without LVH, but with left ventricular diastolic dysfunction. This approach might improve the prognostic stratification of hypertensive subjects and it might be suitable to recognize the subset of patients at a higher risk of cardiovascular disease or events early.

  20. Synergy of circulating miR-212 with markers for cardiovascular risks to enhance estimation of atherosclerosis presence

    Science.gov (United States)

    Lee, Seo Hyun; Hwang, Junha; Shin, Jong Wook; Song, Kyu Sang; Lee, Sukhoon

    2017-01-01

    Synergy of specific microRNAs (miRNAs) with cardiovascular risk factors to estimate atherosclerosis presence in ischemic stroke patients has not been investigated. The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate interaction with other cardiovascular markers to improve the estimation of atherosclerosis presence. We performed a miRNA profiling study using serum of 15 patients with acute ischemic stroke who were classified by the presence of no (n = 8) or severe (n = 7) stenosis on intracranial and extracranial vessels, which identified miR-212, -372, -454, and -744 as miRNAs related with atherosclerosis presence. Of the 4 miRNAs, only miR-212 showed a significant increase in expression in atherosclerosis patients in a validation study (atherosclerotic patients, n = 32, non-atherosclerotic patients, n = 33). Hemoglobin A1c, a high-density lipoprotein cholesterol, and lipoprotein(a), both established risk markers, were independently related with atherosclerosis presence in the validation population. miR-212 enhanced the accuracy of atherosclerosis presence by the three existing markers (three markers, 78.5%; three markers+miR-212, 84.6%, P<0.05) and significantly added to the area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646, P<0.05). The inclusion of miR-212 increased the reclassification index calculated using net reclassification improvement (0.4527, P<0.05) and integrated discrimination improvement (0.0737, P<0.05). We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 enhanced the estimation of atherosclerosis presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the estimation of atherosclerosis using peripheral blood of patients. PMID:28557988

  1. Association between Obesity, hsCRP ≥2 mg/L, and Subclinical Atherosclerosis: Implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis (MESA)

    Science.gov (United States)

    Blaha, Michael J.; Rivera, Juan J.; Budoff, Matthew J.; Blankstein, Ron; Agatston, Arthur; O’Leary, Daniel H.; Cushman, Mary; Lakoski, Susan; Criqui, Michael H.; Szklo, Moyses; Blumenthal, Roger S.; Nasir, Khurram

    2011-01-01

    Objective High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown. Methods and Results We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals. Conclusions High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status. PMID:21474823

  2. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy.

    Science.gov (United States)

    Hartman, Joshua; Frishman, William H

    2014-01-01

    It has recently been appreciated that atherosclerosis is predominantly an inflammatory process. Atherosclerosis begins with a fatty streak, which is made up almost entirely of monocyte-derived macrophages. The development of an atheroma continues as T-cells, mast cells, and other inflammatory cells are recruited to the intima. This collection of inflammatory cells promotes smooth muscle cell replication and extracellular matrix elaboration, thereby increasing the lesion size. Various studies have highlighted that interleukin-6 (IL-6) is an upstream inflammatory cytokine that plays a central role in propagating the downstream inflammatory response responsible for atherosclerosis. IL-6 release is stimulated by acute infections, chronic inflammatory conditions, obesity, and physiologic stress. The high level of IL-6 found in such conditions has a myriad of functions, including hepatic synthesis of acute-phase reactants, activation of endothelial cells, increased coagulation, activation of the hypothalamic-pituitary-adrenal axis, and promotion of lymphocyte proliferation and differentiation. Considering the importance of IL-6 in the development of coronary artery disease, targeting its actions could prove to be beneficial. Individuals with a variant in the IL-6 receptor that impairs classic IL-6 signaling were found to have a decreased risk for coronary heart disease. Tocilizumab is a monoclonal antibody that targets the IL-6 receptor and has been show to alleviate symptoms in patients with rheumatoid arthritis, a disease largely driven by the proinflammatory actions of IL-6. Therefore, further studies are needed to determine the role of tocilizumab and other IL-6 receptor blockers in decreasing the inflammatory response key in the development of atherosclerosis.

  3. Rationale and protocol of a trial for prevention of diabetic atherosclerosis by using antiplatelet drugs: study of Diabetic Atherosclerosis Prevention by Cilostazol (DAPC study

    Directory of Open Access Journals (Sweden)

    Kawamori Ryuzo

    2006-08-01

    Full Text Available Abstract Background Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects. Methods Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day or the cilostazol group (100–200 mg/day in this international, 2-year, prospective follow-up interventional study. Results The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index. Conclusion This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.

  4. Quantifying exposure to calcium and phosphate in ESRD; predictive of atherosclerosis on top of arteriosclerosis?

    NARCIS (Netherlands)

    Jaarsveld, van B.C.; Graaf, van der Y.; Vos, P.F.; Soedamah-Muthu, S.S.

    2010-01-01

    Background: Long-term exposure to hypercalcaemia and hyperphosphataemia leads to media calcification and predicts mortality in patients with end-stage renal disease (ESRD). It is debatable whether this exposure is only a risk factor for arteriosclerosis, or also for superimposed atherosclerosis.

  5. Hemoglobin and atherosclerosis in patients with manifest arterial disease. The SMART-study

    NARCIS (Netherlands)

    Dijk, J. M.; Wangge, G.; Graaf, Y. van der; Bots, M. L.; Grobbee, D. E.; Algra, A.

    2006-01-01

    Decreased hemoglobin levels are known to be associated with an increased risk of coronary mortality and morbidity. This is largely thought to result from the development of left ventricular hypertrophy. Similar remodeling mechanisms of the vessel wall that may result in atherosclerosis are likely to

  6. The immunobiology of CD154-CD40-TRAF interactions in atherosclerosis

    NARCIS (Netherlands)

    Engel, David; Seijkens, Tom; Poggi, Marjorie; Sanati, Maryam; Thevissen, Larissa; Beckers, Linda; Wijnands, Erwin; Lievens, Dirk; Lutgens, Esther

    2009-01-01

    Atherosclerosis is a chronic disease of the large arteries that is responsible for the majority of cardiovascular events. In its pathogenesis, the immune system plays a pivotal role. The effectuation of the immune response through interactions between immune cells that is mediated by co-stimulatory

  7. 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

  8. 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

  9. 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...

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

    NARCIS (Netherlands)

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

    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

  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. The epigenetic memory of monocytes and macrophages as a novel drug target in atherosclerosis

    NARCIS (Netherlands)

    Bekkering, S.; Joosten, L.A.B.; Meer, J.W.M. van der; Netea, M.G.; Riksen, N.P.

    2015-01-01

    PURPOSE: Atherosclerosis is characterized by a persistent inflammation of the arterial wall. Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. After stimulation, monocytes can adopt a long-term proinflammatory phenotype. This nonspecific memory of innate

  13. Aspirin and the risk of cardiovascular events in atherosclerosis patients with and without prior ischemic events.

    Science.gov (United States)

    Bavry, Anthony A; Elgendy, Islam Y; Elbez, Yedid; Mahmoud, Ahmed N; Sorbets, Emmanuel; Steg, Philippe Gabriel; Bhatt, Deepak L

    2017-09-01

    The benefit of aspirin among patients with stable atherosclerosis without a prior ischemic event is not well defined. Aspirin would be of benefit in outpatients with atherosclerosis with prior ischemic events, but not in those without ischemic events. Subjects from the Reduction of Atherothrombosis for Continued Health registry were divided according to prior ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at each clinic visit and considered as a time-varying covariate. The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke. In the group with a prior ischemic event, aspirin use was associated with a marginally lower risk of the primary outcome at a median of 41 months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P = 0.06). In the group without a prior ischemic event, aspirin use was not associated with a lower risk of the primary outcome at a median of 36 months (HR: 1.03, 95% CI: 0.73-1.45, P = 0.86). In this observational analysis of outpatients with stable atherosclerosis, aspirin was marginally beneficial among patients with a prior ischemic event; however, there was no apparent benefit among those with no prior ischemic event. © 2017 Wiley Periodicals, Inc.

  14. Genetic Determinants of Atherosclerosis, Obesity and Energy Balance in Consomic Mice

    Science.gov (United States)

    Spiezio, Sabrina H.; Amon, Lynn M.; McMillen, Timothy S.; Vick, Cynthia M.; Houston, Barbara A.; Caldwell, Mark; Ogimoto, Kayoko; Morton, Gregory J.; Kirk, Elizabeth A.; Schwartz, Michael W.; Nadeau, Joseph H.; LeBoeuf, Renée C.

    2014-01-01

    Metabolic diseases such as obesity and atherosclerosis result from complex interactions between environmental factors and genetic variants. A panel of chromosome substitution strains (CSSs) was developed to characterize genetic and dietary factors contributing to metabolic diseases and other biological traits and biomedical conditions. Our goal here was to identify quantitative trait loci (QTLs) contributing to obesity, energy expenditure and atherosclerosis. Parental strains C57BL/6 and A/J together with a panel of 21 CSSs derived from these progenitors were subjected to chronic feeding of rodent chow and atherosclerotic (females) or diabetogenic (males) test diets, and evaluated for a variety of metabolic phenotypes including several traits unique to this report, namely fat pad weights, energy balance and atherosclerosis. A total of 297 QTLs across 35 traits were discovered, two of which provided significant protection from atherosclerosis, and several dozen QTLs modulated body weight, body composition and circulating lipid levels in females and males. While several QTLs confirmed previous reports, most QTLs were novel. Finally, we applied the CSS quantitative genetic approach to energy balance, and identified three novel QTLs controlling energy expenditure and one QTL modulating food intake. Overall, we identified many new QTLs and phenotyped several novel traits in this mouse model of diet-induced metabolic diseases. PMID:25001233

  15. Perivascular spaces are associated with atherosclerosis: an insight from the Northern Manhattan Study.

    Science.gov (United States)

    Gutierrez, J; Rundek, T; Ekind, M S V; Sacco, R L; Wright, C B

    2013-09-01

    Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis. Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis. The studied sample included 706 participants (mean age, 72.6 ± 8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (β = 0.01 per year, P = spaces. Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies.

  16. Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission.

    Science.gov (United States)

    Wang, Qilong; Zhang, Miao; Torres, Gloria; Wu, Shengnan; Ouyang, Changhan; Xie, Zhonglin; Zou, Ming-Hui

    2017-01-01

    Metformin is a widely used antidiabetic drug that exerts cardiovascular protective effects in patients with diabetes. How metformin protects against diabetes-related cardiovascular diseases remains poorly understood. Here, we show that metformin abated the progression of diabetes-accelerated atherosclerosis by inhibiting mitochondrial fission in endothelial cells. Metformin treatments markedly reduced mitochondrial fragmentation, mitigated mitochondrial-derived superoxide release, improved endothelial-dependent vasodilation, inhibited vascular inflammation, and suppressed atherosclerotic lesions in streptozotocin (STZ)-induced diabetic ApoE-/- mice. In high glucose-exposed endothelial cells, metformin treatment and adenoviral overexpression of constitutively active AMPK downregulated mitochondrial superoxide, lowered levels of dynamin-related protein (Drp1) and its translocation into mitochondria, and prevented mitochondrial fragmentation. In contrast, AMPK-α2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE-/-/AMPK-α2-/- mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission. Consistently, mitochondrial division inhibitor 1, a potent and selective Drp1 inhibitor, reduced mitochondrial fragmentation, attenuated oxidative stress, ameliorated endothelial dysfunction, inhibited inflammation, and suppressed atherosclerosis in diabetic mice. These findings show that metformin attenuated the development of atherosclerosis by reducing Drp1-mediated mitochondrial fission in an AMPK-dependent manner. Suppression of mitochondrial fission may be a therapeutic approach for treating macrovascular complications in patients with diabetes. © 2017 by the American Diabetes Association.

  17. 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... (MESA) Event Surveillance. Type of Information Request: Renewal (OMB No. 0925-0493). Need and Use of... of appropriate automated, electronic, mechanical, or other technological collection techniques or...

  18. Migraine and subclinical atherosclerosis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Goulart, Alessandra C; Santos, Itamar S; Bittencourt, Márcio S; Lotufo, Paulo A; Benseñor, Isabela M

    2016-08-01

    The relationship between migraine and coronary heart disease (CHD) remains controversial. We aimed to investigate the association of subclinical atherosclerosis and migraine with or without aura compared to a non-migraine subgroup (reference) in a large Brazilian multicentric cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Migraine diagnostic was based on International Headache Society criteria, and aura symptoms were validated by a medical doctor in a sub-sample of the ELSA-Brasil, who also underwent coronary artery calcium score (CAC) and carotid intima-media thickness (C-IMT) evaluations. Subclinical atherosclerosis indexes (CAC and C-IMT) were analyzed as dependent variables and migraine (all, with aura, without aura) as an independent variable in the linear and multinomial logistic regression models adjusted for possible confounders. Of 3217 ELSA participants free from CVD at baseline, we found a migraine frequency of 11.9% (5.1% with aura and 6.8% without aura). Overall, migraineurs were mostly women, younger and had lower frequency of CV risk factors, such as hypertension, diabetes and low HDL-cholesterol, compared to non-migraineurs. The strongest inverse correlation between migraine and subclinical atherosclerosis was verified with CAC score. However, all associations lost their significance after multivariate adjustment. In this cross-sectional evaluation of the ELSA study, migraine was not associated with subclinical atherosclerosis, regardless of aura symptoms. © International Headache Society 2015.

  19. Vitamin E supplementation and atherosclerosis : epidemiological studies in elderly and smokers

    NARCIS (Netherlands)

    Waart, de F.

    2000-01-01

    The antioxidant vitamin E may have beneficial effects on several indicators of human health. We studied the impact on atherosclerosis, immune response and total mortality in smokers and elderly people, who are at risk for increased oxidative stress. Vitamin E may exert its effect on

  20. Longitudinal study on premature atherosclerosis in patients with systemic lupus erythematosus

    NARCIS (Netherlands)

    de Leeuw, Karina; Smit, Andries J.; de Groot, Eric; van Roon, Arie M.; Kallenberg, Cees G.; Bijl, Marc

    2009-01-01

    Objectives: To determine risk factors of accelerated atherosclerosis and progression of intima-media thickness (IMT) in patients with systemic lupus erythematosus (SLE). Methods: 74 SLE patients, age ranging from 13 to 69 years, and 74 age- and sex-matched controls were included. IMT of the common