title: Dysfunctional high-density lipoprotein and the potential of apolipoprotein A-1 mimetic peptides to normalize the composition and function of lipoproteins.
abstract: Although high-density lipoprotein-cholesterol (HDL-C) levels in large epidemiological studies are inversely related to the risk of coronary heart disease (CHD), increasing the level of circulating HDL-C does not necessarily decrease the risk of CHD events, CHD deaths, or mortality. HDL can act as an anti- or a pro-inflammatory molecule, depending on the context and environment. Based on a number of recent studies, it appears that the anti- or pro-inflammatory nature of HDL may be a more sensitive indicator of the presence or absence of atherosclerosis than HDL-C levels. The HDL proteome has been suggested to be a marker, and perhaps a mediator, of CHD. Apolipoprotein A-1 (apoA-I), the major protein in HDL is a selective target for oxidation by myeloperoxidase, which results in impaired HDL function. Improving HDL function through modification of its lipid and/or protein content maybe a therapeutic target for the treatment of CHD and many inflammatory disorders. HDL/apoA-I mimetic peptides may have the ability to modify the lipid and protein content of HDL and convert dysfunctional HDL to functional HDL. This review focuses on recent studies of dysfunctional HDL in animal models and human disease, and the potential of apoA-I mimetic peptides to normalize the composition and function of lipoproteins.
authors.affiliation: Department of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.forename: Christina
authors.initials: C
authors.lastname: Charles-Schoeman
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Murray
authors.initials: M
authors.lastname: Kwon
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Ganapathy
authors.forename: David
authors.initials: D
authors.lastname: Meriwether
authors.forename: Robin
authors.initials: R
authors.lastname: Farias-Eisner
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology* / Q000627:therapeutic use; D032701:Biomimetics; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D010455:Peptides / Q000627:therapeutic use*
chemical_list: D016632:Apolipoprotein A-I; C465468:D-4F peptide; D036341:Intercellular Signaling Peptides and Proteins; C472885:L-4F peptide; D008075:Lipoproteins, HDL; D010455:Peptides; C431648:peptide 5F