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Atherosclerosis susceptible genes

Jin Cai, Gengze Wu, Pedro A Jose, Chunyu Zeng
Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs...
October 14, 2016: Experimental Cell Research
Andrew T Grainger, Michael B Jones, Jing Li, Mei-Hua Chen, Ani Manichaikul, Weibin Shi
BACKGROUND AND AIMS: Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe(-/-) and BALB/cJ-Apoe(-/-) mice in atherosclerotic lesion formation. METHODS: 206 female F2 mice generated from an intercross between the two Apoe(-/-) strains were fed 12 weeks of western diet...
October 6, 2016: Atherosclerosis
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
Peter F Davies, Elisabetta Manduchi, Christian J Stoeckert, Yi-Zhou Jiang
Hemodynamics creates a constantly changing physical and chemical environment to which the arterial endothelium is exquisitely sensitive. Biomechanical stresses are intrinsic to blood flow characteristics and blood pressure and therefore are important considerations in hypertension. Near branching anatomical sites in arteries, blood flow separates from the main flow to undergo complex multi-directional characteristics for a part of each cardiac cycle (collectively referred to as disturbed flow). Atherosclerosis and aneurysmal pathology develop preferentially at disturbed flow locations, particularly when an additional cardiovascular risk factor such as hypercholesterolemia or high blood pressure are present...
September 2016: Journal of Hypertension
Rosalinda Posadas-Sánchez, Ángel René López-Uribe, Carlos Posadas-Romero, Nonanzit Pérez-Hernández, José Manuel Rodríguez-Pérez, Wendy Angélica Ocampo-Arcos, José Manuel Fragoso, Guillermo Cardoso-Saldaña, Gilberto Vargas-Alarcón
The aim of this study was to evaluate the potential use of the I148M/PNPLA3 (rs738409) gene polymorphism as a susceptibility marker for premature coronary artery disease (pCAD) and/or cardiovascular risk factors in Mexican type 2 diabetes mellitus patients (T2DM). The polymorphism was genotyped by 5' exonuclease TaqMan assays in a group of 2572 subjects (1103 with pCAD and 1469 healthy controls) belonging to the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Anthropometric and biochemical measurements were performed in all individuals...
September 3, 2016: Immunobiology
Irma Eloisa Monroy-Muñoz, Javier Angeles-Martinez, Rosalinda Posadas-Sánchez, Teresa Villarreal-Molina, Edith Alvarez-León, Carmina Flores-Dominguez, Guillermo Cardoso-Saldaña, Aida Medina-Urrutia, Juan Gabriel Juárez-Rojas, Carlos Posadas-Romero, Gilberto Vargas Alarcon
The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population...
September 3, 2016: Immunobiology
Jinkwon Kim, Gun Ho Choi, Ki Han Ko, Jung Oh Kim, Seung Hun Oh, Young Seok Park, Ok Joon Kim, Nam Keun Kim
The microRNA (miRNA) is a small non-coding RNA molecule that modulates gene expression at the posttranscriptional level. Platelets have a crucial role in both hemostasis and thrombosis, a condition that can occlude a cerebral artery and cause ischemic stroke. miR-130b, miR-200b, and miR-495 are potential genetic modulators involving platelet production and activation. We hypothesized that single nucleotide polymorphisms (SNPs) in these miRNAs might potentially contribute to the susceptibility to ischemic stroke and post-stroke mortality...
2016: PloS One
Amélie Pinard, Morgane Miltgen, Arnaud Blanchard, Hélène Mathieu, Jean-Pierre Desvignes, David Salgado, Aurélie Fabre, Pauline Arnaud, Laura Barré, Martin Krahn, Philippe Grandval, Sylviane Olschwang, Stéphane Zaffran, Catherine Boileau, Christophe Béroud, Gwenaëlle Collod-Béroud
Adoption of next-generation sequencing (NGS) in a diagnostic context raises numerous questions with regard to identification and reports of secondary variants (SVs) in actionable genes. To better understand the whys and wherefores of these questioning, it is necessary to understand how they are selected during the filtering process and how their proportion can be estimated. It is likely that SVs are underestimated and that our capacity to label all true SVs can be improved. In this context, Locus-specific databases (LSDBs) can be key by providing a wealth of information and enabling classifying variants...
September 7, 2016: Human Mutation
Steven A Lubitz, Jennifer A Brody, Nathan A Bihlmeyer, Carolina Roselli, Lu-Chen Weng, Ingrid E Christophersen, Alvaro Alonso, Eric Boerwinkle, Richard A Gibbs, Joshua C Bis, L Adrienne Cupples, Peter J Mohler, Deborah A Nickerson, Donna Muzny, Marco V Perez, Bruce M Psaty, Elsayed Z Soliman, Nona Sotoodehnia, Kathryn L Lunetta, Emelia J Benjamin, Susan R Heckbert, Dan E Arking, Patrick T Ellinor, Honghuang Lin
Atrial fibrillation (AF) is a morbid and heritable arrhythmia. Over 35 genes have been reported to underlie AF, most of which were described in small candidate gene association studies. Replication remains lacking for most, and therefore the contribution of coding variation to AF susceptibility remains poorly understood. We examined whole exome sequencing data in a large community-based sample of 1,734 individuals with and 9,423 without AF from the Framingham Heart Study, Cardiovascular Health Study, Atherosclerosis Risk in Communities Study, and NHLBI-GO Exome Sequencing Project and meta-analyzed the results...
September 2016: PLoS Genetics
Lihi Eder, Fatima Abji, Cheryl F Rosen, Vinod Chandran, Richard J Cook, Dafna D Gladman
OBJECTIVE: To investigate the association between HLA susceptibility and disease severity markers and the extent of atherosclerosis in patients with psoriatic disease. METHODS: White patients with psoriatic arthritis (PsA) and psoriasis without PsA (PsC) were recruited. An ultrasound of the carotid arteries was performed and the size of each atherosclerotic plaque was measured. The resulting score, the total plaque area (TPA), represented the extent of atherosclerosis...
October 2016: Journal of Rheumatology
M G Pavlatou, A T Remaley, P W Gold
Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan...
August 30, 2016: Translational Psychiatry
Xiaoming Ling, Yansong Zheng, Jing Tao, Zhezhou Zheng, Lidian Chen
BACKGROUND: Ischemic stroke is the main cause of mortality and disability in older people worldwide. Recently epidemiological studies indicate that ischemic stroke is a complex disorder with a strong genetic component. Genome-wide association studies (GWAS) identified several single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) and myocardial infarction (MI) locus in ABO gene. Our study examined the association between four variants in the ABO gene and the risk of ischemic stroke and its subtypes, large-artery atherosclerosis (LAA) and small-vessel diseases (SVD) in the Chinese population...
2016: BMC Neurology
Meritxell Nus, Beatriz Martínez-Poveda, Donal MacGrogan, Rafael Chevre, Gaetano D'Amato, Mauro Sbroggio, Cristina Rodríguez, José Martínez-González, Vicente Andrés, Andrés Hidalgo, José Luis de la Pompa
AIMS: To determine the role of NOTCH during the arterial injury response and the subsequent chronic arterial-wall inflammation underlying atherosclerosis. METHODS AND RESULTS: We have generated a mouse model of endothelial-specific (Cdh5-driven) depletion of the Notch effector RBPJ (ApoE(-/-);RBPJ(flox/flox);Cdh5-Cre(ERT)). Endothelial-specific deletion of RBPJ or systemic deletion of Notch1 in athero-susceptible ApoE(-/-) mice fed a high cholesterol diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus...
August 5, 2016: Cardiovascular Research
Xue-Bin Wang, Ya-di Han, Shrestha Sabina, Ning-Hua Cui, Shuai Zhang, Ze-Jin Liu, Cong Li, Fang Zheng
A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors...
2016: PloS One
Shih-Chi Su, Ming-Ju Hsieh, Yu-Fan Liu, Ying-Erh Chou, Chiao-Wen Lin, Shun-Fa Yang
BACKGROUND: Oral cancer is a common malignancy that is shown to be causally associated with hereditary and acquired factors. ADAMTS14 is a member of the ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin motifs) metalloproteinase family that plays an important role in extracellular matrix (ECM) assembly and degradation. Elevation or deficiency of certain ADAMTS proteinases has been known to be implicated in a wide range of pathological processes including atherosclerosis, arthritis, and cancer...
2016: PloS One
Amir Tajbakhsh, Seyed Mahdi Hassanian, Mohammad Sadegh Khorrami, Alireza Pasdar, Ehsan Tabatabai, Seyed Mohammad Reza Parizadeh, Mostafa Fazeli, Sharareh Gholamin, Gordon A Ferns, Majid Ghayour-Mobarhan, Amir Avan
Cardiovascular disease (CVD) is the leading cause of global mortality. Although extensive efforts have been made to identify valid biomarkers for CVD risk, relatively ¬¬¬few are of proven clinical utility. It is recognized that genetic factors play a major role in determining the susceptibility to CVD. Recent genome-wide-association-studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CVD. Several genetic-polymorphisms have been identified in this region that are highly associated with CVD, and these are clustered around the gene loci for CDKN2B (coding for p15ink4b), CDKN2A (coding for p16ink4a and p14ARF) and the 3' end of CDKN2BAS, which has been termed antisense noncoding RNA in the INK4 locus (ANRIL)...
June 27, 2016: Current Pharmaceutical Design
Federica Rizzi, Costanza Conti, Elena Dogliotti, Annalisa Terranegra, Erika Salvi, Daniele Braga, Flavia Ricca, Sara Lupoli, Alessandra Mingione, Francesca Pivari, Caterina Brasacchio, Matteo Barcella, Martina Chittani, Francesca D'Avila, Maurizio Turiel, Monica Lazzaroni, Laura Soldati, Daniele Cusi, Cristina Barlassina
BACKGROUND: Paraoxonase 1 (PON1) gene polymorphisms and polyphenols intake have been reported independently associated to lipid profile and susceptibility to atherosclerosis and cardiovascular disease. However, the interaction between these factors remains to be investigated. We performed an observational nutrigenetic study to examine whether the interaction between polyphenols and anthocyanins intake and PON1 genetic variants can modulate biomarkers of cardiovascular health in an Italian healthy population...
2016: Journal of Translational Medicine
Sariya Dechamethakun, Masaaki Muramatsu
Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus, dyslipidemia, hypertension and abdominal obesity. This cluster of abnormalities individually and interdependently leads to atherosclerosis and CVD morbidity and mortality. In the past decade, genome-wide association studies (GWASs) have identified a series of cardiometabolic disease-associated variants that can collectively explain a small proportion of the variability...
June 16, 2016: Journal of Human Genetics
Sanaz Eftekhari, Soraya Mehrabi, Fariba Karimzadeh, Mohammad-Taghi Joghataei, Mojtaba Khaksarian, Mahmoud Reza Hadjighassem, Majid Katebi, Mansooreh Soleimani
INTRODUCTION: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS...
April 2016: Basic and Clinical Neuroscience
Pradeep Kumar, Amit Kumar, Mukesh Kumar Srivastava, Shubham Misra, Awadh Kishor Pandit, Kameshwar Prasad
INTRODUCTION: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS...
April 2016: Basic and Clinical Neuroscience
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