Statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases, but
there is increasing evidence that they exert effects by much exceeding the lowering of cholesterol levels. Statins have
antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. These "pleiotropic"
effects stem from their inhibition of prenylation of the small GTP-binding proteins Ras and Rho, and to the disruption, or
depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins modulate
immune responses by altering cytokine levels and by affecting the function of cells involved in both innate and adaptive
responses. Anti-inflammatory and immunosuppressory properties of statins provide the rationale for their potential
application in conditions in which the inflammation and immune response represent key pathogenic mechanisms, such as
antiphospholipid syndrome, rheumatoid arthritis and systemic lupus erythematosus. Reduction of atherosclerosis
progression in autoimmunity is also a very important effect. Statins pathways of action in systemic autoimmune diseases,
and their potential therapeutic use are discussed in this review.
The inhibition of mevalonate pathway by statins impairs modification of Ras and Rho GTPases, which play key roles in
signaling pathways related to tumor formation, metastasis and cell death. There is experimental and clinical evidence that
statins may improve the therapeutic outcome of anticancer drugs. Thus, this review will also discuss recent insights into
the molecular mechanisms underlying the anticancer effects of statins and their assessment as promising candidates for
inclusion into current therapeutic regimens for the treatment of malignant diseases.
Keywords: Statins, autoimmune diseases, atherosclerosis, cardiovascular disease, inflammation, cancer, PLEIOTROPIC EFFECTS, tumor, Haematological Malignancies, Antiphospholipid Syndrome
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