Statins have proved to be a crucial component of cardiovascular disease treatment. Much of their benefit may be unrelated to their cholesterol-lowering properties. A wide array of vasculoprotective actions has been described, the most potent targeting endothelial cells. The relatively strong safety profile of HMG Co-A reductase inhibitors in humans makes them an attractive pharmacologic class to study in other disease processes besides atherosclerosis. Moreover, delineation of the mechanisms involved in mediating their pleiotropic effects generates opportunities to develop novel compounds that can target a more specific pathway, e.g., LFA-1 inhibitors, Rho-kinase inhibitors, GGTase inhibitors, and potentially Akt activators.
Actin stress fibers: Intracellular filaments in vascular endothelial cells formed by polymerization of actin and myosin leading to cell contracture and disruption of barrier function.
Angiogenesis: The process whereby endothelial cells of existing capillaries proliferate to form new vessels.
eNOS (endothelial nitric oxide synthase): The constitutively expressed isoform of the enzyme present in vascular endothelial cells and an important regulator of basal microvascular function.
Pleiotropic effects: A term used to describe the multiple cholesterol-independent actions of statins on vascular function and structure.
Prenylation or isoprenylation: Binding of lipid intermediates to protein signaling molecules.
Statins: A pharmacological class of drugs that competitively inhibit the rate rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase.
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Dr. Girgis is Associate Director of the Pulmonary Hypertension and Lung Transplant Programs at Johns Hopkins University. His research focuses on the effects of statins on vascular remodeling in pulmonary hypertension and is supported by the NIH and Pulmonary Hypertension Association.
Dr. Jacobson is a research fellow in the division of Pulmonary and Critical Care Medicine at Johns Hopkins. He is investigating the effects of statins on cytoskeletal rearrangement in endothelial cells.
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