HDL therapy for cardiovascular diseases: the road to HDL mimetics.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are currently the drug of choice for the clinical management of elevated low-density lipoprotein (LDL) cholesterol. Although statin treatment provides an overall improvement in outcomes, clinical trial data reveal a significant number of cardiac events despite reaching targeted LDL levels. A low serum high-density lipoprotein (HDL) cholesterol level is an independent predictor of cardiovascular risk. Accordingly, there has been interest in determining whether HDL elevation, in addition to LDL lowering, further reduces risk in patients with coronary artery disease. Several commonly prescribed lipid-lowering therapies modestly raise HDL, but their use may be limited by the development of adverse reactions. Emerging data suggest that HDL quality and function may also be significantly reduced by atherosclerosis and other inflammatory diseases. The goal of this review is to discuss the current status of HDL therapeutics, with emphasis on a novel class of agent, the apolipoprotein A-I mimetic peptides, which improve the functional properties of HDL cholesterol.
White
C Roger
CR
Vascular Biology and Hypertension Program, University of Alabama, Birmingham, 1046 Zeigler Research Building, 703 South 19th Street, Birmingham, AL 35294, USA. crwhite@uab.edu
Datta
Geeta
G
Zhang
Zhenghao
Z
Gupta
Himanshu
H
Garber
David W
DW
Mishra
Vinod K
VK
Palgunachari
Mayakonda N
MN
Handattu
Shaila P
SP
Chaddha
Manjula
M
Anantharamaiah
G M
GM
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects*; D002995:Clofibric Acid / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D008074:Lipoproteins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology
C478448:Ac-hE18A-NH(2); D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C465468:D-4F peptide; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D010446:Peptide Fragments; D002995:Clofibric Acid