Current Atherosclerosis Reports

The endothelium is often viewed solely as the barrier that prevents the penetration of circulating lipoproteins into the arterial wall. However, recent research has demonstrated that the endothelium has an important part in regulating circulating fatty acids and lipoproteins, and is in turn affected by these lipids/lipoproteins in ways that appear to have important repercussions for atherosclerosis. Thus, a number of potentially toxic lipids are produced during lipolysis of lipoproteins at the endothelial cell surface. Catabolism of triglyceride-rich lipoproteins creates free fatty acids that are readily taken up by endothelial cells, and, likely through the action of acyl-CoA synthetases, exacerbate inflammatory processes. In this article, we review how the endothelium participates in lipoprotein metabolism, how lipids alter endothelial functions, and how lipids are internalized, processed, and transported into the subendothelial space. Finally, we address the many endothelial changes that might promote atherogenesis, especially in the setting of diabetes.

The health burden of type 2 diabetes mellitus continues to increase worldwide. A substantial portion of this burden is due to the development of cardiovascular disease in patients with diabetes. Recent failures of clinical trials of intensive glucose control to reduce macrovascular events, coupled with reports of potential harm of certain diabetic therapy, have led to increased scrutiny as new diabetic therapies are developed. Incretin peptides are a group of gastrointestinal proteins that regulate glucose metabolism through multiple mechanisms, and incretin-based therapies have been developed to treat type 2 diabetes. These agents include glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-IV (DPP-IV) inhibitors. In addition to effects on glucose homeostasis, growing evidence suggest that these peptides may also affect the cardiovascular system. In this review, we discuss recent findings concerning the potential, yet untested, benefits of incretin-based pharmacotherapy in the treatment of cardiovascular disease.

Exaggerated postprandial hypertriglyceridemia is a risk factor for cardiovascular disease. This metabolic abnormality is principally due to overproduction and/or decreased catabolism of triglyceride-rich lipoproteins (TRLs) and is a consequence of pathogenic genetic variations and other coexistent medical conditions, particularly obesity and insulin resistance. Accumulation of TRL in the postprandial state promotes the formation of small, dense low-density lipoproteins, as well as oxidative stress, inflammation, and endothelial dysfunction, all of which compound the risk of cardiovascular disease. The cardiovascular benefits of lifestyle modification (weight loss and exercise) and conventional lipid-lowering therapies (statins, fibrates, niacin, ezetimibe, and n-3 fatty acid supplementation) could involve their favorable effects on TRL metabolism. New agents, such as dual peroxisome-proliferator-activated receptor α/δ agonists, diacylglycerol, inhibitors of diacylglycerol acyltransferase 1 and microsomal triglyceride transfer protein, antisense oligonucleotides for apolipoprotein B-100 and apolipoprotein C-III, and incretin-based therapies, may enhance the treatment of postprandial lipemia, but their efficacy needs to be tested in clinical end point trials. Further work is required to develop a simple clinical protocol for investigating postprandial lipemia, as well as internationally agreed management guidelines for this type of dyslipidemia.

Atherothrombosis is the underlying cause of several clinical manifestations, such as acute coronary syndromes, cerebrovascular disease, and peripheral artery disease, which together are the leading cause of death in the Western world. Proteins from vascular cells or atherosclerotic plaques that are present in plasma are modified along the different steps of atherosclerotic development and constitute target candidates for vascular research, particularly in the search for novel biological markers of cardiovascular risk. In this review, we summarize proteomic techniques and the most recent results obtained by application of these high-throughput strategies to cardiovascular samples.

Robust evidence is emerging regarding the contribution of sex-specific risk factors to a woman’s unique risk of atherosclerotic cardiovascular disease (ASCVD). This review summarizes the available literature regarding the association of sex-specific risk factors and ASCVD in women. The American College of Cardiology and American Heart Association Guidelines recommend estimation of 10-year risk of a first ASCVD event using the 2013 Pooled Cohort Equations. This can be further personalized by identifying sex-specific risk factors present in a woman’s history. There are multiple vulnerable periods across a woman’s life course that are associated with increased risk of ASCVD. Risk factors across the reproductive life course that have been shown to correlate with higher risk for future ASCVD include early menarche, adverse pregnancy outcomes (such as pre-eclampsia or preterm birth), and early natural or surgical menopause. In addition, certain conditions that are more common among women, including autoimmune diseases, history of chest irradiation, and certain chemotherapies, also need to be considered. Finally, risk assessment can be refined with subclinical disease imaging (coronary calcium score) if there remains uncertainty about clinical management with lipid-lowering therapies for primary prevention after inclusion of these risk enhancers. Risk assessment for ASCVD in women requires a personalized approach that incorporates sex-specific risk factors to guide primary prevention measures, such as lipid-lowering therapies. Coronary calcium score imaging may also help further refine risk assessment, but no clinical trials conducted to date have addressed this question.