« A third of bipolar disorder patients receive inadequate maintenance treatment | Home | No platelet aggregation rebound seen with discontinuation of clopidogrel. »

Italian scientists offer explanation for statin antioxidant effects

By Jeremy Cockerill | January 31, 2010

Scientists in Italy suggest that the beneficial effects of statins on atherosclerosis and cardiovascular disease risk are linked to pleiotropic actions beyond lowering of lipid levels.

The ability of statins to reduce oxidative stress is thought to be one such action and previous research has shown that statin treatment can reduce concentrations of various markers of oxidation including isoprostanes, 8-hydroxydeoxyguanosine, and nitrotyrosine.

However, the mechanisms underlying how statins reduce oxidative stress are unknown.

Francesco Violi, from the University of Rome, and co-workers developed an enzyme-linked immunosorbent assay capable of detecting serum levels of soluble gp91phox, which is the catalytic subunit of phagocyte NADPH oxidase.

The researchers measured soluble gp91phox levels and urinary isoprostane oxidation markers in 30 patients with hypercholesterolemia and 20 healthy volunteers.

The patients were then randomly assigned to a low-fat diet or a low-fat diet plus atorvastatin 10 mg/day for 30 days, and gp91phox and urinary oxidation markers were measured again.

As reported in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, levels of serum soluble gp91phox were significantly higher in patients (35 pg/ml) than in volunteers (16 pg/ml). Concentrations of urinary markers of oxidation were also significantly higher in those with hypercholesterolemia than in those without the condition.

After 30 days of statin therapy, there was an average 33% reduction in gp91phox levels and a 37% reduction in urinary isoprostanes, as well as a 25% reduction in total cholesterol concentration. In contrast, none of these changes were significant in those following a low-fat diet only.

The investigators write: “In conclusion, we provide evidence that in hypercholesterolemia, atorvastatin inhibits oxidative stress via gp91phox downregulation.

“The inhibition of circulating sgp91phox by atorvastatin therefore represents a novel mechanism potentially accounting for the anti-atherosclerotic effect of statins.”