Summary
In the last decades, substantial progress has been made in understanding the relationship
between lipid disorders and prevention of cardiac ischemic disease. Statins competitively
inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial
to cholesterol biosynthesis. Statins have long been thought to exert their benefits
by reducing cholesterol synthesis, but the fact that mevalonate is the precursor of
isoprenoids that regulate diverse cellular functions has led investigators to examine
pleiotropic effects for these agents. Statins have never been shown to be involved
in the immune response, although two clinical trials have suggested that in heart
transplant patients, statin therapy has beneficial effects on the incidence of cardiac
rejection, coronary vasculopathy, and survival.
Major Histocompatibility Complex class II (MHC-II) molecules, which affect the immune
response and organ rejection after transplantation, may be induced by the pro-inflammatory
cyto-kine interferon gamma (IFN-γ). Recently, it has been demonstrated that statins
repress the induction of MHC-II by IFN-γ in vitro, and thus may suggest a potential
role for statins as immunosuppressive agents in vivo. Indeed, two recent in vivo studies
performed on different animal models provide further evidence that statin-treatment
positively influence immunological disorders.
This publication was partially financed by Serono Foundation for the Advancement of
Medical Science.
Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February
6-9, 2003 in Geneva, Switzerland.
Keywords
Atherosclerosis - cytokines - immunity (auto-) - inflammatory mediators - lipid mediators
