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Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway.
Clin Exp Pharmacol Physiol. 2010 Feb; 37(2):156-61.CE

Abstract

1. Rosiglitazone is widely used in the treatment of Type 2 diabetes. However, in recent years it has become evident that the therapeutic effects of peroxisome proliferator-activated receptor gamma ligands reach far beyond their use as insulin sensitizers. Recently, the ability of rosiglitazone pretreatment to induce cardioprotection following ischaemia-reperfusion (I/R) has been well documented; however, the protective mechanisms have not been elucidated. In the present study, examined the role of the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway in rosiglitazone cardioprotection following I/R injury. 2. Mice were pretreated with 3 mg/kg per day rosiglitazone for 14 days before hearts were subjected to ischaemia (30 min) and reperfusion (2 h). Wortmannin (1.4 mg/kg, i.p.), an inhibitor of PI3-K, was administered 10 min prior to myocardial I/R. Then, activation of the PI3-K/Akt/glycogen synthase kinase (GSK)-3alpha signalling pathway was examined. The effects of PI3-K inhibition on rosiglitazone-induced cardioprotection were also evaluated. 3. Compared with control rats, the ratio of infarct size to ischaemic area (area at risk) and the occurrence of sustained ventricular fibrillation in rosiglitazone-pretreated rats was significantly reduced (P < 0.05). Rosiglitazone pretreatment attenuated cardiac apoptosis, as assessed by ELISA to determine cardiomyocyte DNA fragmentation. Rosiglitazone pretreatment significantly increased levels of phosphorylated (p-) Akt and p-GSK-3alpha in the rat myocardium. Pharmacological inhibition of PI3-K by wortmannin markedly abolished the cardioprotection induced by rosiglitazone. 4. These results indicate that rosiglitazone-induced cardioprotection in I/R injury is mediated via a PI3-K/Akt/GSK-3alpha-dependent pathway. The data also suggest that modulation of PI3-K/Akt/GSK-3alpha-dependent signalling pathways may be a viable strategy to reduce myocardial I/R injury.

Authors+Show Affiliations

Department of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19566839

Citation

Zhang, Xue-Jiao, et al. "Rosiglitazone-induced Myocardial Protection Against Ischaemia-reperfusion Injury Is Mediated Via a Phosphatidylinositol 3-kinase/Akt-dependent Pathway." Clinical and Experimental Pharmacology & Physiology, vol. 37, no. 2, 2010, pp. 156-61.
Zhang XJ, Xiong ZB, Tang AL, et al. Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway. Clin Exp Pharmacol Physiol. 2010;37(2):156-61.
Zhang, X. J., Xiong, Z. B., Tang, A. L., Ma, H., Ma, Y. D., Wu, J. G., & Dong, Y. G. (2010). Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway. Clinical and Experimental Pharmacology & Physiology, 37(2), 156-61. https://doi.org/10.1111/j.1440-1681.2009.05232.x
Zhang XJ, et al. Rosiglitazone-induced Myocardial Protection Against Ischaemia-reperfusion Injury Is Mediated Via a Phosphatidylinositol 3-kinase/Akt-dependent Pathway. Clin Exp Pharmacol Physiol. 2010;37(2):156-61. PubMed PMID: 19566839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway. AU - Zhang,Xue-Jiao, AU - Xiong,Zi-Bo, AU - Tang,An-Li, AU - Ma,Hong, AU - Ma,Yue-Dong, AU - Wu,Jing-Guo, AU - Dong,Yu-Gang, Y1 - 2009/06/29/ PY - 2009/7/2/entrez PY - 2009/7/2/pubmed PY - 2010/6/9/medline SP - 156 EP - 61 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 37 IS - 2 N2 - 1. Rosiglitazone is widely used in the treatment of Type 2 diabetes. However, in recent years it has become evident that the therapeutic effects of peroxisome proliferator-activated receptor gamma ligands reach far beyond their use as insulin sensitizers. Recently, the ability of rosiglitazone pretreatment to induce cardioprotection following ischaemia-reperfusion (I/R) has been well documented; however, the protective mechanisms have not been elucidated. In the present study, examined the role of the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway in rosiglitazone cardioprotection following I/R injury. 2. Mice were pretreated with 3 mg/kg per day rosiglitazone for 14 days before hearts were subjected to ischaemia (30 min) and reperfusion (2 h). Wortmannin (1.4 mg/kg, i.p.), an inhibitor of PI3-K, was administered 10 min prior to myocardial I/R. Then, activation of the PI3-K/Akt/glycogen synthase kinase (GSK)-3alpha signalling pathway was examined. The effects of PI3-K inhibition on rosiglitazone-induced cardioprotection were also evaluated. 3. Compared with control rats, the ratio of infarct size to ischaemic area (area at risk) and the occurrence of sustained ventricular fibrillation in rosiglitazone-pretreated rats was significantly reduced (P < 0.05). Rosiglitazone pretreatment attenuated cardiac apoptosis, as assessed by ELISA to determine cardiomyocyte DNA fragmentation. Rosiglitazone pretreatment significantly increased levels of phosphorylated (p-) Akt and p-GSK-3alpha in the rat myocardium. Pharmacological inhibition of PI3-K by wortmannin markedly abolished the cardioprotection induced by rosiglitazone. 4. These results indicate that rosiglitazone-induced cardioprotection in I/R injury is mediated via a PI3-K/Akt/GSK-3alpha-dependent pathway. The data also suggest that modulation of PI3-K/Akt/GSK-3alpha-dependent signalling pathways may be a viable strategy to reduce myocardial I/R injury. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/19566839/Rosiglitazone_induced_myocardial_protection_against_ischaemia_reperfusion_injury_is_mediated_via_a_phosphatidylinositol_3_kinase/Akt_dependent_pathway_ L2 - https://doi.org/10.1111/j.1440-1681.2009.05232.x DB - PRIME DP - Unbound Medicine ER -