Faculty Collaboration Database

High-Density Lipoprotein Functionality as a New Pharmacological Target on Cardiovascular Disease: Unifying Mechanism That Explains High-Density Lipoprotein Protection Toward the Progression of Atherosclerosis. J Cardiovasc Pharmacol 2018 Jun;71(6):325-331

Date

03/13/2018

Pubmed ID

29528874

DOI

10.1097/FJC.0000000000000573

Scopus ID

2-s2.0-85051788295 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

The formation of the atherosclerotic plaque that is characterized by the accumulation of abnormal amounts of cholesterol-loaded macrophages in the artery wall is mediated by both inflammatory events and alterations of lipid/lipoprotein metabolism. Reverse transport of cholesterol opposes the formation and development of atherosclerotic plaque by promoting high density lipoprotein (HDL)-mediated removal of cholesterol from peripheral macrophages and its delivery back to the liver for excretion into the bile. Although an inverse association between HDL plasma levels and the risk of cardiovascular disease (CVD) has been demonstrated over the years, several studies have recently shown that the antiatherogenic functions of HDL seem to be mediated by their functionality, not always associated with their plasma concentrations. Therefore, assessment of HDL function, evaluated as the capacity to promote cell cholesterol efflux, may offer a better prediction of CVD than HDL levels alone. In agreement with this idea, it has recently been shown that the assessment of serum cholesterol efflux capacity (CEC), as a metric of HDL functionality, may represent a predictor of atherosclerosis extent in humans. The purpose of this narrative review is to summarize the current evidence concerning the role of cholesterol efflux capacity that is important for evaluating CVD risk, focusing on pharmacological evidences and its relationship with inflammation. We conclude that HDL therapeutics are a promising area of investigation but strategies for identifying efficacy must move beyond the idea of simply raising static HDL-cholesterol levels and toward methods of measuring the dynamics of HDL particle remodeling and the generation of lipid-free apolipoprotein A-I (apoA-I). In this way, apoA-I, unlike mature HDL, can promote the greatest extent of cholesterol efflux relieving cellular cholesterol toxicity and the inflammation it causes.

Author List

Favari E, Thomas MJ, Sorci-Thomas MG

Authors

Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Inflammatory Agents
Anticholesteremic Agents
Apolipoprotein A-I
Arteries
Atherosclerosis
Cholesterol, HDL
Disease Progression
Drug Design
Drug Discovery
Humans
Macrophages, Peritoneal
Plaque, Atherosclerotic
Risk Factors