Cross-talk between statins and PPARalpha in cardiovascular diseases: clinical evidence and basic mechanisms.
Although a change in lifestyle is the first choice in controlling cardiovascular risk, lipid-lowering drugs are effective in normalizing different forms of atherogenic dyslipidemia. Although statins are a class of drugs which primarily lower low-density lipoprotein cholesterol, fibrates decrease triglycerides, normalize the low-density lipoprotein cholesterol profile, and increase high-density lipoprotein cholesterol. As lipids are important determinants for cardiovascular diseases, these drugs reduce cardiovascular morbidity. However, a number of recent studies indicate that, in addition to their lipid-normalizing activities, statins and fibrates exhibit pleiotropic actions, such as inhibit inflammation, improve endothelial function, suppress the production of reactive oxygen species, etc. Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis, whereas fibrates are activators of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). The similarity between the pleiotropic effects of statins and fibrates is remarkable and suggests a mechanistic link between these two classes of drugs. Here we discuss recent data on the cross-talk between statins and PPARalpha agonists and the mechanisms behind these actions.
Paumelle
Réjane
R
INSERM U545, Institut Pasteur de Lille, Boulevard du Pr. Jules Leclerc, Lille, France. rejane.paumelle@pasteur-lille.fr
Staels
Bart
B
D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002995:Clofibric Acid / Q000494:pharmacology; D050171:Dyslipidemias / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D047493:PPAR alpha / Q000187:drug effects*; D015398:Signal Transduction
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047493:PPAR alpha; D002995:Clofibric Acid