Atherosclerosis

Background and aimsCirculating PCSK9 is a crucial regulator of cholesterol metabolism. Loss-of-function variants in PCSK9 are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and reduced cardiovascular disease (CVD) risk, while gain-of-function variants correlate with elevated LDL-C concentrations and increased CVD risk. This study investigated whether genetically determined LDL-C levels, proxied by four PCSK9 genetic variants, influence common carotid arte...

Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental,1-6 genetic,7 and observational8,9 data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Here, we measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy and explored associations...

Micro- and nanoplastics (MNPs) are increasingly detected in human tissues, yet their causal contribution to cardiovascular disease remains poorly understood. Here we show that oral exposure to polyethylene (PE) and polyvinyl chloride (PVC) -- the most abundant polymers found in human atheromas -- accelerates atherosclerosis in ApoE-/-mice through distinct, polymer-specific molecular mechanisms. While both polymers increased plaque burden and reduced contractile smooth muscle cell (SMC) markers, ...

ImportanceSmoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood. ObjectiveTo determine the effect of smoking on risk of coronary artery disease, peripheral artery disease, and large-artery stroke. DesignMendelian randomization study using summary statistics from genome-wide associations of smoking (up to 462,690 indivi...

TEXT ABSTRACTO_ST_ABSBackgroundC_ST_ABSTraditional cardiovascular risk calculators estimate population-level risk but perform less reliably at the individual level and do not capture biological processes that underlie early atherogenesis. Monocyte activation and platelet-monocyte interactions contribute to early atherogenesis, yet their potential as biomarkers of silent disease in asymptomatic adults has not been defined. The aim of this study was to investigate their utility in prediction of ea...

BackgroundAtherosclerosis predominantly affects men and is the underlying cause of coronary artery disease (CAD) and myocardial infarction (MI). Recent studies show that mosaic loss of chromosome Y (LOY) in blood is associated with all major causes of death, including CAD and MI. However, the relation between LOY and subclinical atherosclerosis remains unclear. This study aims to investigate associations between the male-specific LOY and atherosclerosis. MethodsTo examine associations between h...

Background and AimsProliferation of arterial smooth muscle cells (SMCs) and their modulation to alternative mesenchymal phenotypes is a central mechanism in the growth of atherosclerotic lesions. The underlying processes have been studied extensively in mouse models, but a detailed analysis of when and where modulated SMCs accumulate in human atherosclerosis is lacking. The present study mapped modulated SMC subtypes during the progression of human coronary atherosclerosis and explored their ass...

BackgroundPeripheral arterial disease (PAD) is the 3rd leading type of atherosclerotic disease (ASD) morbidity. Arterial stiffness is intimately connected to the onset and progression of peripheral artery disease (PAD). The role of arterial stiffening on flow-mediated atherosclerotic plaque formation is not well understood. The objective of this study is to discover endothelial cell (EC) pathways under PAD conditions and test the modifiability of these pathways on ASD. MethodsPAD conditions in ...

BackgroundInflammatory processes are a key cause of atherosclerosis and cardiovascular diseases. Complement system has been implicated but evidence is less clear. We tested whether atherosclerosis severity, plaque types, and vascular region are associated with mRNA expression of genes encoding proteins of the complement system and investigated the cell-specific expression of the most differentially expressed transcripts in plaque macrophages, fibroblasts, and endothelial, smooth muscle, Schwann,...

BackgroundAcute coronary syndrome (ACS) is caused by arterial thrombosis and is associated with sustained activation of coagulation. Clotting requires interactions of coagulation factors with aminophospholipids (aPL): phosphatidylserine (PS) and phosphatidylethanolamine (PE) on membrane surfaces. The aPL composition of circulating membranes in coronary disease has not been characterized. Furthermore, the contribution of external-facing aPL to elevated thrombotic risk in ACS is unknown. Methods ...

AimThe aim of the study was to investigate the role of genetic variants in young patients (aged <50 years) with myocardial infarction (MI) and a family history of premature atherosclerosis. Methods and ResultsThe studied group consisted of 70 patients aged 26-49 (mean 43.1, SD {+/-}4.3), 17 women and 53 men, with MI and with a family history of premature atherosclerosis, defined as MI or ischaemic stroke in first-degree relatives at age <65 years in women or <55 years in men. The total DNA was ...

Coronary artery disease (CAD) and peripheral artery disease (PAD) are common and dangerous conditions that are both driven by atherosclerosis. Despite sharing many major risk factors, their disease pathophysiology is not fully understood. In this study, we aimed to better distinguish common vs. unique biological pathways underlying CAD and PAD by proteomics profiling plasma samples from a subset of participants in the Project Baseline Health Study (PBHS). We identified 14 proteins associated wit...

BACKGROUNDVascular calcification significantly influences the onset and outcome of cardiovascular events, yet no effective treatment currently exists. Dysfunction of osteoclastic macrophages contributes to the formation of calcification. Our previous studies have shown that sonodynamic therapy (SDT) can rapidly reverse atherosclerotic plaques by targeting macrophages. This study aimed to investigate the effect of SDT on reducing early or mild vascular calcification by modulating the function of ...

BackgroundPeripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We conducted detailed metabolic profiling to identify biomarkers for the risk of developing PAD and compared with risk of CAD to explore common and unique risk factors for these different vascular diseases. MethodsWe measured blood biomarkers using nuclear magnetic resonance metabolomics in five Finnish prospective general-population cohorts (FINRISK 1997, 2002, 2007...

ObjectiveWe aimed to evaluate the association between inflammatory markers and coronary plaque features on coronary computed tomography angiography (CCTA) among asymptomatic individuals. MethodsBaseline data from Miami Heart Study -- an ongoing prospective community-based study of a primary prevention cohort from the Greater Miami Area without prior known CAD -- were used for this cross-sectional analysis. Independent variables included high-sensitivity C-reactive protein (hsCRP; <2 vs [&ge;] 2...

AimsCurrent risk prediction tools are not accurate enough to identify most individuals at high coronary risk. On the other hand, oxidized low-density lipoproteins (ox-LDLs) and miRNAs are actively involved in atherosclerosis. Our aim was to examine the association of ox-LDL-induced miRNAs with coronary artery disease (CAD), and to assess their predictive capacity of future CAD. Methods and resultsHuman endothelial and vascular smooth muscle cells were treated with oxidized or native LDLs (nLDL)...

IntroductionCarotid artery geometry may contribute to the development of atherosclerotic carotid artery disease (ACD). Prior reports associated ACD with narrow bifurcation angles, tortuous Common Carotid Arteries (CCA), and large bulbs. Our objective was to determine whether deviations in these geometric features at baseline can help predict stenosis severity at follow-up. MethodsA total of 20 human subjects (59{+/-}16 years old, range 31-85 years) with a 4.7{+/-}2.3 year (range 2.0-11.4 years)...

BackgroundCarbohydrate-restricted diets are gaining popularity, including among lean individuals. In these populations, a lipid phenotype often emerges comprising elevated LDL cholesterol (LDL-C), alongside elevated HDL-C and low triglycerides, termed the lean mass hyper-responder (LMHR). ObjectiveTo evaluate one-year coronary plaque progression in LMHRs and near-LMHRs. MethodsThis prospective study followed 100 participants who developed the triad of high LDL-C, high HDL-C, and low triglyceri...

BackgroundFamilial hypercholesterolemia (FH) is an autosomal dominant disorder associated with a markedly increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Genetic and molecular factors, including microRNAs (miRNAs), may serve as biomarkers to improve disease risk prediction. miRNAs are key regulators of biological processes involved in cardiovascular pathology. This study aimed to identify miRNAs that, combined with clinical variables, enhance ASCVD prediction in asymp...

Clonal hematopoiesis of indeterminate potential (CHIP) occurs as a result of acquired mutations in bone marrow progenitor cells. CHIP confers a twofold risk of atherosclerotic cardiovascular disease (ASCVD). However, there is limited data regarding specific cardiovascular phenotypes in this population. We recruited patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed next generation sequencing to determine CHIP status. Multivariable logistic reg...