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Pathogenesis and pathophysiology of Atherosclerosis

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345 papers 25 to 100 followers Theory and research into the molecular causes and hemodynamics consequences of the atherosclerotic lesion
By Gregory Gustafson Interventional Cardiologist
Jin Sug Kim, Weon Kim, Jong Shin Woo, Tae Won Lee, Chun Gyoo Ihm, Yang Gyoon Kim, Joo Young Moon, Sang Ho Lee, Myung Ho Jeong, Kyung Hwan Jeong
OBJECTIVE: A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). METHOD: This study was based on the Korea Acute Myocardial Infarction Registry database...
2016: PloS One
Meyer Elbaz, Julien Faccini, Vanina Bongard, Cécile Ingueneau, Dorotea Taraszkiewicz, Bertrand Perret, Jean Ferrières, Jean-Bernard Ruidavets, Cécile Vindis
BACKGROUND: High-density lipoproteins (HDLs) are highly heterogeneous particles, and the specific contribution of each subclass to the prediction of clinical outcome in coronary artery disease (CAD) remains controversial. OBJECTIVE: To examine the relationship between HDL subclass profile and mortality in patients with CAD, using a new and rapid electrophoretic quantitative method for the assessment of HDL particle size phenotype. METHODS: We investigated 403 patients with CAD admitted for cardiovascular examination in the context of evaluation and management of CAD...
November 2016: Archives of Cardiovascular Diseases
Kishore Kumar Gundapaneni, Nivas Shyamala, Rajesh Kumar Galimudi, Sanjib Kumar Sahu, Surekha Rani Hanumanth
INTRODUCTION: Coronary Artery Disease (CAD) a multifactorial chronic heart disease and the most frequent cause of death and disabling symptoms worldwide, occurs due to the formation of atheromatous lipid rich plaques in the arteries. Statins, which inhibit cholesterol biosynthesis, have both pleiotropic and Low-Density Lipoprotein (LDL)-lowering properties. Atorvastatin is one of the choices for the primary and secondary prevention of cardiovascular disease and management of hypercholesterolaemia...
June 2016: Journal of Clinical and Diagnostic Research: JCDR
M Johanneke van den Berg, Yolanda van der Graaf, Gert Jan de Borst, L Jaap Kappelle, Hendrik M Nathoe, Frank L J Visseren
Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study...
September 15, 2016: American Journal of Cardiology
Stacey Knight, Arthur T Maness, Sue M Dintelman, Benjamin D Horne
BACKGROUND: Many landmark genetic breakthroughs, including the recent discovery of PCSK-9 inhibitor drugs, were accomplished with substantial contributions from evaluation of pedigrees. Finding and ascertaining high-value pedigrees is not trivial and requires considerable time and cost. Here, we describe the creation of the Intermountain Genealogy Registry for use in studying the genetics of cardiovascular and other diseases. METHODS: Using publicly available pedigree records and probabilistic linkage techniques, we created a genealogy of ≈23 million records that we linked to 3...
July 16, 2016: Human Heredity
Paul Nioi, Asgeir Sigurdsson, Gudmar Thorleifsson, Hannes Helgason, Arna B Agustsdottir, Gudmundur L Norddahl, Anna Helgadottir, Audur Magnusdottir, Aslaug Jonasdottir, Solveig Gretarsdottir, Ingileif Jonsdottir, Valgerdur Steinthorsdottir, Thorunn Rafnar, Dorine W Swinkels, Tessel E Galesloot, Niels Grarup, Torben Jørgensen, Henrik Vestergaard, Torben Hansen, Torsten Lauritzen, Allan Linneberg, Nele Friedrich, Nikolaj T Krarup, Mogens Fenger, Ulrik Abildgaard, Peter R Hansen, Anders M Galløe, Peter S Braund, Christopher P Nelson, Alistair S Hall, Michael J A Williams, Andre M van Rij, Gregory T Jones, Riyaz S Patel, Allan I Levey, Salim Hayek, Svati H Shah, Muredach Reilly, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Lambertus A Kiemeney, Arshed A Quyyumi, Daniel J Rader, William E Kraus, Nilesh J Samani, Oluf Pedersen, Gudmundur Thorgeirsson, Gisli Masson, Hilma Holm, Daniel Gudbjartsson, Patrick Sulem, Unnur Thorsteinsdottir, Kari Stefansson
BACKGROUND: Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. METHODS: We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent...
June 2, 2016: New England Journal of Medicine
Clint L Miller, Milos Pjanic, Ting Wang, Trieu Nguyen, Ariella Cohain, Jonathan D Lee, Ljubica Perisic, Ulf Hedin, Ramendra K Kundu, Deshna Majmudar, Juyong B Kim, Oliver Wang, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Themistocles L Assimes, Stephen B Montgomery, Eric E Schadt, Johan L M Björkegren, Thomas Quertermous
Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations...
July 8, 2016: Nature Communications
Annelise Genoux, Laeticia Lichtenstein, Jean Ferrières, Thibaut Duparc, Vanina Bongard, Paul-Louis Vervueren, Guillaume Combes, Dorota Taraszkiewicz, Meyer Elbaz, Michel Galinier, Bertrand Nassar, Jean-Bernard Ruidavets, Bertrand Perret, Laurent O Martinez
BACKGROUND: Epidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection...
August 23, 2016: BMC Medicine
Wei Yang, Fu Liang Ng, Kenneth Chan, Xiangyuan Pu, Robin N Poston, Meixia Ren, Weiwei An, Ruoxin Zhang, Jingchun Wu, Shunying Yan, Haiteng Situ, Xinjie He, Yequn Chen, Xuerui Tan, Qingzhong Xiao, Arthur T Tucker, Mark J Caulfield, Shu Ye
Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A...
July 2016: PLoS Genetics
Hiroaki Sukegawa, Yuichiro Maekawa, Shinsuke Yuasa, Atsushi Anzai, Masaki Kodaira, Makoto Takei, Fumiya Sano, Ikuko Ueda, Takashi Kawakami, Kentaro Hayashida, Takashi Kohno, Shun Kohsaka, Takayuki Abe, Keiichi Fukuda
BACKGROUND: Besides its potent plasma cholesterol-lowering activity, statin treatment has several other important effects, including lowering high-sensitive C-reactive protein (hs-CRP), levels, and stabilizing risk factors of atherosclerosis, thereby reducing the risk of cardiovascular events. Our aim in this study was to identify how intensive statin therapy can affect plasma levels of inflammatory markers over the long term. METHODS AND RESULTS: We used a prospective, randomized, open blinded-endpoint design...
August 2016: Coronary Artery Disease
Reijo Laaksonen, Kim Ekroos, Marko Sysi-Aho, Mika Hilvo, Terhi Vihervaara, Dimple Kauhanen, Matti Suoniemi, Reini Hurme, Winfried März, Hubert Scharnagl, Tatjana Stojakovic, Efthymia Vlachopoulou, Marja-Liisa Lokki, Markku S Nieminen, Roland Klingenberg, Christian M Matter, Thorsten Hornemann, Peter Jüni, Nicolas Rodondi, Lorenz Räber, Stephan Windecker, Baris Gencer, Eva Ringdal Pedersen, Grethe S Tell, Ottar Nygård, Francois Mach, Juha Sinisalo, Thomas F Lüscher
AIMS: The aim was to study the prognostic value of plasma ceramides (Cer) as cardiovascular death (CV death) markers in three independent coronary artery disease (CAD) cohorts. METHODS AND RESULTS: Corogene study is a prospective Finnish cohort including stable CAD patients (n = 160). Multiple lipid biomarkers and C-reactive protein were measured in addition to plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1). Subsequently, the association between high-risk ceramides and CV mortality was investigated in the prospective Special Program University Medicine-Inflammation in Acute Coronary Syndromes (SPUM-ACS) cohort (n = 1637), conducted in four Swiss university hospitals...
July 1, 2016: European Heart Journal
Hagai Tavori, Ilaria Giunzioni, Irene M Predazzi, Deanna Plubell, Anna Shivinsky, Joshua Miles, Rachel M Devay, Hong Liang, Shirya Rashid, MacRae F Linton, Sergio Fazio
AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of hepatic low-density lipoprotein (LDL) receptors (LDLR), thereby, decreasing hepatocyte LDL-cholesterol (LDL-C) uptake. However, it is unknown whether PCSK9 has effects on atherogenesis that are independent of lipid changes. The present study investigated the effect of human (h) PCSK9 on plasma lipids, hepatic lipogenesis, and atherosclerotic lesion size and composition in transgenic mice expressing hPCSK9 (hPCSK9tg) on wild-type (WT), LDLR⁻/⁻, or apoE⁻/⁻ background...
May 15, 2016: Cardiovascular Research
Sven Hermann, Michael T Kuhlmann, Andrea Starsichova, Sarah Eligehausen, Klaus Schäfers, Jörg Stypmann, Klaus Tiemann, Bodo Levkau, Michael Schäfers
UNLABELLED: The hyperlipidemic mouse model HypoE/SRBI(-/-) has been shown to develop occlusive coronary atherosclerosis followed by myocardial infarctions and premature deaths in response to high-fat, high-cholesterol diet (HFC). However, the causal connection between myocardial infarctions and atherosclerotic plaque rupture events in the coronary arteries has not been investigated so far. The objective of this study was to assess whether diet-induced coronary plaque ruptures trigger atherothrombotic occlusions, resulting in myocardial infarctions in HFC-fed HypoE/SRBI(-/-) mice...
September 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Shixi Wang, Weidong He, Caijin Wang
OBJECTIVE: Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-23a and the expression of epidermal growth factor receptor (EGFR) in the pathogenesis of patients with coronary heart disease to further explore the mechanism involved in its vasculogenesis. METHOD: Three different cohorts, including 13 acute myocardial infarction (AMI) patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-23a in patients with myocardial ischemia and also the relationship between plasma miR-23a and severity of coronary stenosis...
August 2016: Cardiovascular Therapeutics
Jin M Cheng, Rohit M Oemrawsingh, Hector M Garcia-Garcia, Eric Boersma, Robert-Jan van Geuns, Patrick W Serruys, Isabella Kardys, K Martijn Akkerhuis
BACKGROUND AND AIMS: Experimental studies have suggested that proprotein convertase substilisin/kexin type 9 (PCSK9) might directly promote inflammatory processes contributing to atherosclerosis by mechanisms independent of low-density lipoprotein (LDL) cholesterol levels. This study aims to investigate the association between serum PCSK9 levels and the fraction and amount of necrotic core tissue in coronary atherosclerotic plaque, as assessed by intravascular ultrasound virtual histology (IVUS-VH) imaging...
May 2016: Atherosclerosis
Michal Laufer Perl, Ariel Finkelstein, Miri Revivo, Shlomo Berliner, Itzhak Herz, Itay Rabinovich, Tomer Ziv-Baran, Dalit Gotler, Gad Keren, Shmuel Bana, Yaron Arbel
BACKGROUND: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable. OBJECTIVES: To evaluate the association of biomarkers with coronary and carotid disease. METHODS: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery...
February 2016: Israel Medical Association Journal: IMAJ
Frederick E Dewey, Viktoria Gusarova, Colm O'Dushlaine, Omri Gottesman, Jesus Trejos, Charleen Hunt, Cristopher V Van Hout, Lukas Habegger, David Buckler, Ka-Man V Lai, Joseph B Leader, Michael F Murray, Marylyn D Ritchie, H Lester Kirchner, David H Ledbetter, John Penn, Alexander Lopez, Ingrid B Borecki, John D Overton, Jeffrey G Reid, David J Carey, Andrew J Murphy, George D Yancopoulos, Aris Baras, Jesper Gromada, Alan R Shuldiner
BACKGROUND: Higher-than-normal levels of circulating triglycerides are a risk factor for ischemic cardiovascular disease. Activation of lipoprotein lipase, an enzyme that is inhibited by angiopoietin-like 4 (ANGPTL4), has been shown to reduce levels of circulating triglycerides. METHODS: We sequenced the exons of ANGPTL4 in samples obtain from 42,930 participants of predominantly European ancestry in the DiscovEHR human genetics study. We performed tests of association between lipid levels and the missense E40K variant (which has been associated with reduced plasma triglyceride levels) and other inactivating mutations...
March 24, 2016: New England Journal of Medicine
Catherine E Handy, Chintan S Desai, Zeina A Dardari, Mouaz H Al-Mallah, Michael D Miedema, Pamela Ouyang, Matthew J Budoff, Roger S Blumenthal, Khurram Nasir, Michael J Blaha
OBJECTIVES: This study sought to determine if coronary artery calcium (CAC) is associated with incident noncardiovascular disease. BACKGROUND: CAC is considered a measure of vascular aging, associated with increased risk of cardiovascular and all-cause mortality. The relationship with noncardiovascular disease is not well defined. METHODS: A total of 6,814 participants from 6 MESA (Multi-Ethnic Study of Atherosclerosis) field centers were followed for a median of 10...
May 2016: JACC. Cardiovascular Imaging
Wijtske Annema, Arnold von Eckardstein
Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially anti-atherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles...
July 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Vanessa Frodermann, Matthias Nahrendorf
No abstract text is available yet for this article.
March 16, 2016: European Heart Journal
2016-03-20 20:52:13
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