Apolipoprotein mimetic peptides: Mechanisms of action as anti-atherogenic agents

Abstract

Apolipoprotein mimetic peptides are short synthetic peptides that share structural, as well as biological features of native apolipoproteins. The early positive clinical trials of intravaenous preparations of apoA-I, the main protein component of high density lipoproteins (HDL), have stimulated great interest in the use of apolipoprotein mimetic peptides as possible therapeutic agents. Currently, there are a wide variety of apolipoprotein mimetic peptides at various stages of drug development. These peptides typically have been designed to either promote cholesterol efflux or act as anti-oxidants, but they usually exert other biological effects, such as anti-inflammatory and anti-thrombotic effects. Uncertainty about which of these biological properties is the most important for explaining their anti-atherogenic effect is a major unresolved question in the field. Structure-function studies relating the in vitro properties of these peptides to their ability to reduce atherosclerosis in animal models may uncover the best rationale for the design of these peptides and may lead to a better understanding of the mechanisms behind the atheroprotective effect of HDL.

In vivo efficacy of HDL-like nanolipid particles containing multivalent peptide mimetics of apolipoprotein A-I

“…Thus, there has been considerable interest in employing a design approach that involves shorter peptides that mimic apoA-I ( 21 ). From numerous studies on apoA-I mimetic peptides based on one or two amphiphilic ␣ -helical segments (22)(23)(24)(25)(26), a wide range of peptide sequences have been found that are more-or-less effective in various aspects of apoA-I mimicry. Many of these peptides have no sequence homology to apoA-I, as they capitalize on an amphiphilic ␣ -helical structural motif, and some are composed of all D -amino acids ( 21 ).…”

The A’s Have It

“…In addition to its role in reverse cholesterol transport, HDL particles have increasingly been recognized to modulate innate and adaptive immune responses, as well as to have antiinflammatory, antioxidant, antithrombotic, and antifibrotic properties. [6][7][8] This Ahead of the Curve article reviews the evidence supporting the concept of developing apoA-I mimetic peptides for the treatment of asthma.…”

ATP-Binding Cassette Transporter 1 Attenuates Ovalbumin-Induced Neutrophilic Airway Inflammation

“…apoA-I is a key component of highdensity lipoprotein (HDL) particles that mediates reverse cholesterol transport out of cells and thereby protects against atherosclerosis (11,12). Cholesterol is transported out of cells by interactions between HDL and the ATP-binding cassette (ABC), subfamily A, member 1 (ABCA1), as well as other transporters, such as ABCG1 and SR-BI (12).…”

“…Cholesterol is transported out of cells by interactions between HDL and the ATP-binding cassette (ABC), subfamily A, member 1 (ABCA1), as well as other transporters, such as ABCG1 and SR-BI (12). Furthermore, the ability of endothelial cells to bind, internalize, and transcytose lipidfree apoA-I is mediated by ABCA1 (13).…”