The promise of apolipoprotein A-I mimetics.
OBJECTIVE
Synthetic high-density lipoprotein (HDL) and apolipoprotein (apo) A-I mimetic peptides emulate many of the atheroprotective biological functions attributed to HDL and can modify atherosclerotic disease processes. Administration of these agents as HDL replacement or modifying therapy has tremendous potential of providing new treatments for cardiovascular disease. Progress in the understanding of these agents is discussed in this review.


RESULTS
Prospective, observational, and interventional studies have convincingly demonstrated that elevated serum levels of high-density lipoprotein-cholesterol (HDL-C) are associated with reduced risk for coronary heart disease (CHD). Although traditional pharmacological agents have shown modest utility in raising HDL levels and reducing CHD risk, use of HDL and apo A-I mimetics provides novel therapies to not only increase HDL levels, but to also influence HDL functionality. Evidence developed over the last several years has identified a number of pathways affected by synthetic HDL and apoA-I mimetic peptides, including enhancing reverse cholesterol transport and reducing oxidation and inflammation that directly influence the progression and regression of atherosclerotic disease.


CONCLUSIONS
Clinical trials of relatively short-term synthetic HDL infusion into patients with CHD demonstrate beneficial effects. Use of apo A-I mimetic peptides could potentially overcome some of the limitations associated with use of the intact apo. Studies to establish the most efficacious peptides, optimal dosing regimens, and routes of administration are needed. Use of apo A-I mimetic peptides shows great promise as a therapeutic modality for HDL replacement and enhancing HDL function in treatment of patients with CHD.
Mendez
Armando J
AJ
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. amendez2@med.miami.edu
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000517:prevention & control; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D032701:Biomimetics / Q000639:trends; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D017433:Protein Structure, Secondary
D016632:Apolipoprotein A-I; D000960:Hypolipidemic Agents; D010446:Peptide Fragments