Role of GW0742 A PPARβ/δ Agonist on Coronary Angiogenesis in Control and Diabetic Rats

Background: Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors; comprising of three isoforms in human: PPARβ/δ, PPARγ and PPARα. Since PPARs affect on cytokines and growth factors, it is suggested that PPARs may be regulated angiogenesis process. In this study, we investigated the hypothesis that activation of PPARβ /δ by GW0742 can restore coronary angiogenesis in diabetic and control rats. Methods: Twenty-four male rats were randomly divided into four groups. For induction of diabetes we used streptozotocin (50 mg/kg). The groups were as follows: group 1: control rats were given placebo, group 2: control rats were given GW0742 (1 mg/kg/day) subcutaneously, group 3: diabetic rats were given placebo and group 4: diabetic rats were given GW0742 (1 mg/kg/day) subcutaneously. After 21 days capillary density was evaluated in cardiac muscle by immunohistochemistry. Findings: The mean capillary density in cardiac muscles of diabetic rats were lower than control (P = 0.08). GW0742 administration could restore capillary density of the heart in diabetic rats (215.82 ± 11.3 versus121.71 ± 13.32 number of capillaries per mm2) while could not alter capillary density in control rats (156.3 ± 8.97 versus 153.78 ± 11.08 number of capillaries per mm2). Conclusion: this study showed that diabetes is associated by reduced capillary density in the heart. PPARβ/δ activation by GW0742 could restore coronary angiogenesis in diabetic rats while did not change angiogenesis in non diabetic rats.