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Diab Vasc Dis Res. 2017 Mar;14(2):152-162. doi: 10.1177/1479164116679081. Epub 2017 Jan 23.

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

Author information

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.

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

PMID:
28111985
PMCID:
PMC5305042
DOI:
10.1177/1479164116679081
[Indexed for MEDLINE]
Free PMC Article

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