Cyclooxygenases are involved in the metabolism of arachidonic acid to prostaglandins (PGs) and thromboxane (TX) A 2 (6). In vascular biology, the two major products of COX are TXA 2 , which is mainly formed by the constitutive form of COX, COX-1 in activated platelets, and prostacyclin or PGI 2 , which is mainly produced in vascular cells by COX-1 and the inducible form of COX, COX-2 (7, 8). TXA 2 participates in platelet aggregation and vascular contraction, whereas PGI 2 acts as an antiaggregant for platelets and a vasodilator. PGI 2 plays an important role in vascular physiology as illustrated by the therapeutic effect of stable analogs of PGI 2 such as iloprost (9). Platelets from patients suffering from hypercholesterolemia are characterized by hypersensitivity to various aggregating agents. Notarbartolo et al. (10) have shown that simvastatin decreased platelet aggregation in hypercholesterolemic subjects and supported a decrease in the thromboxane platelet production, although the underlying mechanism of the statin effect on platelet function remains unclear.In this study, we demonstrated in human aortic smooth muscle cells (hASMC) that two different statins, mevastatin and lovastatin, increased COX-2 expression and PGI 2 formation. We further demonstrated using selective inhibitors of geranylgeranyltransferases and modulators of Rho GTPases that geranylgeranylated proteins such as Rho seem to be responsible for COX-2 down-regulation, which is prevented by statins.

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