Beneficial vascular and metabolic effects of peroxisome proliferator-activated receptor-alpha activators.
Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-alpha that is highly expressed in skeletal muscle and heart, where it promotes beta-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-alpha regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, PPAR-alpha may exert direct antiatherogenic actions in the vascular wall. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated nitric oxide production from the endothelium and decreased blood flow to skeletal muscle. Thus, improvement in insulin sensitivity leads to improved endothelial function. This may be an additional mechanism whereby fibrates decrease the incidence of coronary heart disease. Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. In this review, we discuss the mechanisms underlying the vascular and metabolic effects of fibrates that may act synergistically to prevent or regress atherosclerosis and coronary heart disease.
Han
Seung Hwan
SH
Division of Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea.
Quon
Michael J
MJ
Koh
Kwang Kon
KK
D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control*; D002995:Clofibric Acid / Q000494:pharmacology*; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D047493:PPAR alpha / Q000187:drug effects / Q000502:physiology*; D012307:Risk Factors
D002316:Cardiotonic Agents; D008074:Lipoproteins; D047493:PPAR alpha; D002995:Clofibric Acid