机构：[1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院[2]Department of Anesthesiology, Kunming Tongren Hospital, Kunming, China[3]Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA[4]Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA[5]Section of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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.
基金：
F. Hoffmann-La Roche LtdHoffmann-La Roche; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81160035, 81460044]; Yunnan Provincial Science and Technology Department [2014HB031, 2011FZ119]; Yunnan Provincial Bureau of Health [D201211]; AstraZenecaAstraZeneca; Boehringer IngelheimBoehringer Ingelheim; Eli LillyEli Lilly; Novo NordiskNovo Nordisk; Takeda PharmaceuticalsTakeda Pharmaceutical Company Ltd
第一作者机构：[1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China[*1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, #295 Xichang Road, Kunming 650032, Yunnan Province, China
推荐引用方式(GB/T 7714)：
Chen Yan,Chen Hongmei,Birnbaum Yochai,et al.Aleglitazar, a dual peroxisome proliferator-activated receptor- and - agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia[J].DIABETES & VASCULAR DISEASE RESEARCH.2017,14(2):152-162.doi:10.1177/1479164116679081.
APA：
Chen, Yan,Chen, Hongmei,Birnbaum, Yochai,Nanhwan, Manjyot K.,Bajaj, Mandeep...&Qian, Jinqiao.(2017).Aleglitazar, a dual peroxisome proliferator-activated receptor- and - agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia.DIABETES & VASCULAR DISEASE RESEARCH,14,(2)
MLA：
Chen, Yan,et al."Aleglitazar, a dual peroxisome proliferator-activated receptor- and - agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia".DIABETES & VASCULAR DISEASE RESEARCH 14..2(2017):152-162
