Pleiotropic effects of statins in atherosclerosis and diabetes

S Bellosta, N Ferri, L Arnaboldi, F Bernini - Diabetes care, 2000 - search.proquest.com
S Bellosta, N Ferri, L Arnaboldi, F Bernini
Diabetes care, 2000search.proquest.com
RESULTS—Fluvastatin. simvastatin, lovastatin, atorvastatin, and cerivastatin, but not
pravastatin, dose—dependently decrease smooth muscle cell (SMC) migration and
proliferation Moreover, statins are able to reduce cholesterol accumulation in macrophages
in vitro by block-ing cholesterol esterification and endocytosis of modified lipoproteins and
matrix—degrading enzyme secretion. This in vitro inhibition was completely prevented by
mevalortate and partially by all—trans farnesol and all-trans geranylgeraniol, confirming the …
RESULTS—Fluvastatin. simvastatin, lovastatin, atorvastatin, and cerivastatin, but not pravastatin, dose—dependently decrease smooth muscle cell (SMC) migration and proliferation Moreover, statins are able to reduce cholesterol accumulation in macrophages in vitro by block-ing cholesterol esterification and endocytosis of modified lipoproteins and matrix—degrading enzyme secretion. This in vitro inhibition was completely prevented by mevalortate and partially by all—trans farnesol and all-trans geranylgeraniol, confirming the spectfic role of isoprenoid metabolites (probably through prenylated proteinlsl) in regulating these cellular events. The inhibitory effect of statins on STVIC proliferation has been shown in different models of proliferating cells, such as cultured arterial myocytes and rapidly proliferating carotid and femoral inti» ma] lesions in rabbits, independently of their ability to reduce plasma cholesterol. Finally, ex vivo studies showed that sera from fluvastatin-treated patients interfere with SMC proliferation.
CONCLUS'ONS—These results suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase inhibitors exert a direct anti-atherosclerotic effect in the arterial wall, beyond their effects on plasma lipids that could translate into a tnore significant prevention of cardiovascular disease. These findings provide a basis for the beneficial effect ofstatins in clin-ical trials also involving diabetic patients—a population with a higher absolute risk of recur-rent cardiovascular events.
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