The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation.
Statin-induced inhibition ofHMG-CoA reductase reduces cholesterol production and prevents the formation of many non-steroidal isoprenoid compounds, such as farnesylpyrophosphate and geranylgeranylpyrophosphate, that act as lipid attachments for the post-translational modification of various proteins, including the G-proteins and transcription factors involved in a number of cell processes. However, the blockade of isoprenylation elicited by statin treatment also has biological effects on cell function that go beyond the decrease in cholesterol synthesis: these are the so-called "pleiotropic" effects that mainly relate to vascular function. Endothelial dysfunction is an independent predictor of cardiovascular events that correlates with inflammation markers/mediators and robust predictors of cardiovascular diseases such as increased high-sensitivity C-reactive protein levels. The results of in vivo and in vitro studies indicate that the statins have beneficial effects unrelated to cholesterol lowering, such as improving endothelial function, increasing myocardial perfusion, and enhancing the availability of nitric oxide. This review describes the pleiotropic effects of statins that may be involved in modulating/preventing endothelial dysfunction and inflammatory processes, as well as the cellular and molecular mechanisms through which they improve endothelial function.
Gelosa
Paolo
P
Department of Pharmacological Sciences, University of Milan, Milano, Italy.
Cimino
Mauro
M
Pignieri
Alice
A
Tremoli
Elena
E
Guerrini
Uliano
U
Sironi
Luigi
L
D000818:Animals; D021941:Caveolae / Q000201:enzymology; D004194:Disease; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide