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

Yan Chen, Hongmei Chen, Yochai Birnbaum, Manjyot K. Nanhwan, Mandeep Bajaj, Yumei Ye, Jinqiao Qian

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)152-162
Number of pages11
JournalDiabetes and Vascular Disease Research
Volume14
Issue number2
DOIs
StatePublished - Mar 1 2017

Fingerprint

Peroxisome Proliferator-Activated Receptors
Cardiac Myocytes
Hyperglycemia
Small Interfering RNA
Apoptosis
Cytochromes
Caspase 3
Reactive Oxygen Species
Antioxidants
aleglitazar
Knockout Mice
Cell Survival
Glucose

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ Agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia. / Chen, Yan; Chen, Hongmei; Birnbaum, Yochai; Nanhwan, Manjyot K.; Bajaj, Mandeep; Ye, Yumei; Qian, Jinqiao.

In: Diabetes and Vascular Disease Research, Vol. 14, No. 2, 01.03.2017, p. 152-162.

Research output: Contribution to journalArticle

Chen, Yan ; Chen, Hongmei ; Birnbaum, Yochai ; Nanhwan, Manjyot K. ; Bajaj, Mandeep ; Ye, Yumei ; Qian, Jinqiao. / Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ Agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia. In: Diabetes and Vascular Disease Research. 2017 ; Vol. 14, No. 2. pp. 152-162.
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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.",
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AU - Chen, Yan

AU - Chen, Hongmei

AU - Birnbaum, Yochai

AU - Nanhwan, Manjyot K.

AU - Bajaj, Mandeep

AU - Ye, Yumei

AU - Qian, Jinqiao

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AB - 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.

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KW - cardiomyocytes

KW - hyperglycaemia

KW - peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ agonist

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