2. Academic Validation
  3. Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia

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

  • Diab Vasc Dis Res. 2017 Mar;14(2):152-162. doi: 10.1177/1479164116679081.
Yan Chen 1,  Hongmei Chen 2,  Yochai Birnbaum 3,  Manjyot K Nanhwan 4,  Mandeep Bajaj 5,  Yumei Ye 4,  Jinqiao Qian 1
Affiliations

Affiliations

  • 1 1 Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 2 2 Department of Anesthesiology, Kunming Tongren Hospital, Kunming, China.
  • 3 3 Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
  • 4 4 Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
  • 5 5 Section of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
PMID: 28111985 DOI: 10.1177/1479164116679081
Abstract

Purpose: To assess the effects of Aleglitazar on hyperglycaemia-induced Apoptosis.

Methods: We incubated human cardiomyocytes, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout or wild-type mice in normoglycaemic or hyperglycaemic conditions (glucose 25 mM). Cells were treated with different concentrations of Aleglitazar for 48 h. 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-α or peroxisome proliferator-activated receptor-γ.

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-γ 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-α alone and short interfering RNA against peroxisome proliferator-activated receptor-γ alone and completely blocked by short interfering RNA to both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ.

Conclusion: Aleglitazar protects cardiomyocytes against hyperglycaemia-induced Apoptosis by combined activation of both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in a short-term vitro model.

Keywords

Aleglitazar; apoptosis; cardiomyocytes; hyperglycaemia; peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ agonist.

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