Abstract 12955: A New Pleiotropic Effect of Statin : Induction of CD39 Expression at Atherosclerotic Lesions in vivo and in vitro.
Background: CD39 inhibits platelet aggregation by hydrolyzing extracellular ATP and ADP. We previously reported that CD39 gene eluting stent prevents in-stent thrombosis and neointimal growth, and accelerates reendothelialization. Statins are well known to be anti-atherosclerotic, but it is not known whether or not statins augment CD39 expression as one of their pleiotropic effects.
Methods and Results: We evaluated whether the oral administration of statin (rosuvastatin, 10mg/kg/day) upregulates CD39 mRNA expression in the atherosclerotic plaque and prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. CD39 mRNA levels in the abdominal aorta after 3 months rosuvastatin treatment were significantly higher than without (1.73±1.57 vs 0.51±0.85 /β-actin, p<0.05, Fig A). Histological examination revealed the plaque area of abdominal aorta was significantly smaller in WHHL rabbits with 6 months rosuvastatin than without (0.80±0.21 vs 1.45±0.18 mm2, p<0.05). Next, we evaluated 29 directional coronary atherectomy (DCA) samples obtained from patients with angina pectoris (AP). CD39 mRNA levels in DCA samples were significantly higher in patients with statin than without (2.51±0.75 vs 1.29±0.15 /β-actin, p<0.05, Fig B). CD39 mRNA levels were tend to be higher in DCA samples from patients with stable AP than with unstable AP (1.90±0.37 vs 1.16±0.17 /β-actin, p=0.20). CD39 mRNA expression was not affected by coronary risk factors and other drugs. In cell culture, CD39 mRNA levels were higher in HUVEC cultured with rosuvastatin (10μ M, 24 hours) than without (1.00±0.16 vs 0.50±0.21 /β-actin, p<0.05). On the other hand, eNOS mRNA levels were not affected by rosuvastatin.
Conclusion: Statin augments CD39 gene expression in the atherosclerotic lesion as its new pleiotropic effects, which at least partly contributes to statin's anti-atherosclerotic property.
- © 2011 by American Heart Association, Inc.