title: Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review.
abstract: Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.
authors.affiliation: Department of Medicine, Divisions of Cardiovascular Disease, Gerontology, Geriatric Medicine University of Alabama at Birmingham, Birmingham, AL.
authors.forename: C Roger
authors.initials: CR
authors.lastname: White
authors.affiliation: Palliative Care, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: David W
authors.initials: DW
authors.lastname: Garber
authors.affiliation: Palliative Care, University of Alabama at Birmingham, Birmingham, AL Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D040761:Biomimetic Materials / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents
keywords: apolipoprotein A-I; apolipoprotein E; atherosclerosis; high density lipoprotein; inflammation; low density lipoprotein; mimetic peptides