Atorvastatin reduces Fas and Fas ligand expression in a rabbit experimental model of atherosclerosis

Different studies have shown that HMG-CoA reductase inhibitors reduce cardiovascular mortality, but the mechanisms are not clear. The presence of apoptotic cells is a characteristic of atherosclerotic lesions, the cellular content reduction in the plaque being a vulnerability marker. A principal mechanism of cell death activation is the Fas-Fas ligand system. In this paper, we have studied the Fas-FasL expression in a rabbit atherosclerotic model. We have observed that Fas and FasL are highly expressed in atherosclerotic lesions, in the intima and also in the media. Furthermore, we have explored the effect of atorvastatin, an HMG-CoA reductase inhibitor, on the lesion size, content of inflammatory cells (macrophages) and Fas-FasL expression. We have observed that atorvastatin reduces the size of the lesion, macrophage infiltration and Fas-FasL expression. Fas and FasL downregulation suggests a possible new mechanism for atorvastatin in the prevention of cellular content decrease in the lesion and a better stability of the atherosclerotic plaques.