Authors: Takuya Shida Takashi Nozawa Mitsuo Sobajima Hiroyuki Ihori Akira Matsuki Hiroshi Inoue
Publish Date: 2013/08/25
Volume: 29, Issue: 4, Pages: 532-541
Abstract
Diabetic cardiomyopathy is associated with increased oxidative stress and vascular endothelial dysfunction which lead to coronary microangiopathy We tested whether statininduced redox imbalance improvements could ameliorate diabetic cardiomyopathy and improve coronary microvasculature in streptozotocininduced diabetes mellitus DM Fluvastatin 10 mg/kg/day or vehicle was orally administered for 12 weeks to rats with or without DM Myocardial oxidative stress was assessed by NADPH nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox and gp91phox mRNA expression and myocardial 8isoprostaglandin F2α PGF2α levels Myocardial vascular densities were assessed using antiCD31 and antiαsmooth muscle actin SMA antibodies Fluvastatin did not affect blood pressure or plasma cholesterol but attenuated increased left ventricular LV minimum pressure and ameliorated LV systolic dysfunction in DM rats in comparison with vehicle LV dP/dt 89 ± 18 vs 54 ± 10 × 103 mmHg/s P 005 Myocardial oxidative stress increased in DM but fluvastatin significantly reduced p22phox and gp91phox mRNA expression and myocardial PGF2α levels Fluvastatin enhanced myocardial endothelial nitric oxide synthase eNOS protein levels and increased eNOS vascular endothelial growth factor and hypoxiainducible factor1α mRNA expression CD31positive cell densities were lower in DM rats than in nonDM rats 284 ± 132 vs 486 ± 43/field P 005 and fluvastatin restored the number 578 ± 183/field although there were no significant differences in SMApositive cell densities between groups Fluvastatin did not affect cardiac function oxidative stress or vessel densities in nonDM rats These results suggest that beneficial effects of fluvastatin on diabetic cardiomyopathy might result at least in part from improving coronary microvasculature through reduction in myocardial oxidative stress and upregulation of angiogenic factor
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