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.