Myocardial capillary density in normal and diabetic male rats: Effect of bezafibrate

Cardiovascular disease is the common cause of mortality in diabetic subjects. Recently, it is indicated that peroxisome proliferator-activated receptors (PPARs) agonists have beneficial effect on cardiovascular system especially on angiogenesis. PPARs have three isotypes: PPARα, PPARβ/δ and PPARγ. In this study, we evaluated the effect of bezafibrate as pan PPAR agonist on myocardial capillary density in type I diabetic rats. Eighteen male wistar rats were randomly divided into three groups (n=6 each): control, diabetic and diabetic+bezafibrate (400 mg/kg/day) by gavage every day. Diabetes was induced by a single dose of streptozotocin (55 mg/kg), intraperitoneally. After 21 days, capillary density in the myocardial tissue was evaluated by immunohistochemical staining and reported as capillaries per mm2. Blood samples were taken before and after the experiment. Diabetes was associated by lower serum nitric oxide (NO) concentration and reduced myocardial capillary density compared to control group (121.71 ± 13.32 vs. 158.78 ± 11.08 /mm2; P<0.05). Administration of bezafibrate significantly increased serum NO level and improved angiogenesis in myocardial tissue of diabetic animals (170.24 ± 15.76 vs.121.71 ± 13.32 /mm2; P<0.05). There was a positive correlation between serum NO concentration and myocardial capillary density (r=0.90). Activation of all isotypes of PPAR by bezafibrate improves heart capillary density in diabetic animals and it seems that it can be considered for treatment or prevention of coronary heart disease in diabetic subjects.