Abstract 12757: Fluvastatin-induced Improvement of Redox Imbalance Ameliorates Diabetic Cardiomyopathy in Association With Improving Coronary Microvasculature
Background: Diabetic cardiomyopathy is associated with increased oxidative stress as well as vascular endothelial dysfunction leading to myocardial microangiopathy. We tested the hypothesis that the statin-induced improvement of redox imbalance could ameliorate diabetic cardiomyopathy in association with improving coronary microvasculature in streptozotocin-induced diabetic (DM) rats.
Method: Fluvastatin (10mg/Kg/day) or vehicle was orally administered for 12 weeks to DM and non-DM rats. Myocardial oxidative stress was assessed by myocardial 8-iso-prostaglandin F2α (PGF2α) and NADPH oxidase subunit p22phox and gp91phox mRNA expression. Myocardial vascular densities were assessed by immunohistochemistry using anti-CD31 and anti-α smooth muscle actin (SMA) antibodies, and fibrosis by TGFβ1 expression and tissue stained with silius red.
Result: Fluvastatin did not affect blood pressure or plasma cholesterol level, but attenuated an increase in LV minimum pressure and ameliorated LV dysfunction in DM compared to vehicle (LVdP/dt, 8.9±1.8 vs 5.4±1.0 ×103mmHg/s, p<0.01). Myocardial oxidative stress increased in DM, but fluvastatin significantly reduced levels of PGF2α (14±9 vs 180±102 ng/g tissue) and p22phox and gp91phox mRNA expression. Fluvastatin enhanced myocardial eNOS protein level in association with increasing eNOS and VEGF mRNA expression. The number of CD31-positive cell densities was lower in DM than in non-DM (48.6±4.3 vs 28.4±13.2 /field, p<0.05), but fluvastatin restored this reduction in DM (57.8±18.3). There were no differences in SMA-positive cell densities between DM and non-DM. Fluvastatin inhibited myocardial fibrosis and TGFβ1 expression of DM. In non-DM, however, fluvastatin did not affect any of cardiac function, oxidative stress, vessel densities or fibrosis.
Conclusion: We conclude that a long-term treatment with fluvastatin improved diabetic cardiomyopathy and this improvement results, at least in part, from a reduction in oxidative stress leading to the attenuation of diabetes-induced deteriorationin myocardial microvasculature.
- © 2012 by American Heart Association, Inc.