[The non-lipid effects of statins].
In the past 15 years statins have gained recognition as one of the successful drugs in cardiovascular therapy and are now regarded as important as the beta blocking agents and ACE inhibitors. Since the publication of the Scandinavian Simvastatin Survival Study in 1994, the clinical application of statins has become increasingly widespread. Numerous large-scale clinical end-point trials have demonstrated that statin therapy reduces cardiovascular morbidity and mortality. Their beneficial therapeutic effects, besides their lipid lowering role, have been attributed to their non-lipid modifying ability, called the pleiotropic effect. The clinical consequences of the latter are not well understood, simply because differentiating between their lipid modifying and pleiotropic effects is not possible in vivo. In this article the authors summarize the evidence of the pleiotropic effects based on results of the latest in vitro experiments. They describe the influence of statins on endothelial dysfunction and thrombus formation, their anti-inflammatory, plaque-stabilizing and antioxidant effects, as well as their CRP and angiogenesis modifying non-lipid effects. The authors further discuss the effects of these drugs on tumors, osteoporosis and dementia. Although all members of the statin family inhibit the same enzyme in the cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), their various pharmacokinetic properties, and tissue selectivity (lipophilicity and hydrophilicity) are responsible for their different pleiotropic effects.
Paragh
György
G
Debreceni Egyetem, Orvos- és Egészségtudományi Centrum Altalános Orvostudományi Kar, I. sz. Belgyógyászati Klinika. paragh@ibel.dote.hu
Márk
László
L
Katona
Evelin
E
D000368:Aged; D000544:Alzheimer Disease / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000401:mortality; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010024:Osteoporosis / Q000378:metabolism / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9