Statins and the vasculopathy of systemic sclerosis: potential therapeutic agents?
It has been postulated that endothelial cell injury is the initiating event in the pathogenesis of systemic sclerosis, causing attraction, attachment, migration and infiltration of activated T-cells and subsequent production of cytokines and growth factors. As a result of the action of these cytokines and growth factors, chemoattraction of fibroblasts into the vessel wall and transdifferentiation of resident fibroblasts and smooth muscle cells into myofibroblasts occur leading to fibrosis and exaggerated collagen deposition in the vessel wall. To date, the therapeutic options for the vasculopathy of systemic sclerosis have been limited to drugs that cause vasodilation and inhibit platelet aggregation and only a few agents have shown vascular remodeling effects. Therapeutic agents that could potentially modify the course of this vasculopathy may have a disease-modifying effect, particularly, if instituted in the early stages of the disease. Extensive recent studies have shown that statins display numerous effects independent of their well-established lipid-lowering effect that may be of potential benefit in preventing vascular injury and ischemic vascular events. Here, we review the current literature, which suggests that statins may have a modifying effect on the vasculopathy of systemic sclerosis.
Derk
Chris T
CT
Division of Rheumatology, Department of Medicine, Thomas Jefferson University, 613 Curtis Bldg, 1015 Walnut Street, Philadelphia, PA 19107-5541, USA. Chris.Derk@jefferson.edu
Jimenez
Sergio A
SA
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors