Aleglitazar, a dual peroxisome proliferator-activated receptor- and - agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia

作者：Chen, Yan; Chen, Hongmei; Birnbaum, Yochai; Nanhwan, Manjyot K.; Bajaj, Mandeep; Ye, Yumei; Qian, Jinqiao^*

来源：Diabetes and Vascular Disease Research, 2017, 14(2): 152-162.

DOI：10.1177/1479164116679081

• Aleglitazar
• peroxisome proliferator-activated receptor- and peroxisome proliferator-activated receptor- agonist
• hyperglycaemia
• cardiomyocytes
• apoptosis

Purpose: To assess the effects of Aleglitazar on hyperglycaemia-induced apoptosis. @@@ Methods: We incubated human cardiomyocytes, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor- knockout or wild-type mice in normoglycaemic or hyperglycaemic conditions (glucose 25mM). Cells were treated with different concentrations of Aleglitazar for 48h. We measured viability, apoptosis, caspase-3 activity, cytochrome-C release, total antioxidant capacity and reactive oxygen species formation in the treated cardiomyocytes. Human cardiomyocytes were transfected with short interfering RNA against peroxisome proliferator-activated receptor- or peroxisome proliferator-activated receptor-. @@@ Results: Aleglitazar attenuated hyperglycaemia-induced apoptosis, caspase-3 activity and cytochrome-C release and increased viability in human cardiomyocyte, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor- knockout and wild-type mice. Hyperglycaemia reduced the antioxidant capacity and Aleglitazar significantly blunted this effect. Hyperglycaemia-induced reactive oxygen species production was attenuated by Aleglitazar in both human cardiomyocyte and wild-type mice cardiomyocytes. Aleglitazar improved cell viability in cells exposed to hyperglycaemia. The protective effect was partially blocked by short interfering RNA against peroxisome proliferator-activated receptor- alone and short interfering RNA against peroxisome proliferator-activated receptor- alone and completely blocked by short interfering RNA to both peroxisome proliferator-activated receptor- and peroxisome proliferator-activated receptor-. @@@ Conclusion: Aleglitazar protects cardiomyocytes against hyperglycaemia-induced apoptosis by combined activation of both peroxisome proliferator-activated receptor- and peroxisome proliferator-activated receptor- in a short-term vitro model.

• 出版日期2017-3
• 单位昆明医科大学