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Rosuvastatin postconditioning protects isolated hearts against ischemia-reperfusion injury: The role of radical oxygen species, PI3K-Akt-GSK-3β pathway, and mitochondrial permeability transition pore.
Cardiovasc Ther. 2017 Feb; 35(1):3-9.CT

Abstract

AIMS

Glycogen synthase kinase-3β (GSK-3β) and mitochondrial permeability transition pore (mPTP) play an important role in myocardial ischemia-reperfusion injury. The aim of this study was to investigate whether postconditioning with rosuvastatin is able to reduce myocardial ischemia-reperfusion injury and clarify the potential mechanisms.

METHODS

Isolated rat hearts underwent 30 minutes of ischemia and 60 minutes of reperfusion in the presence or absence of rosuvastatin (1-50 nmol/L). The activity of signaling pathway was determined by Western blot analysis, and Ca2+ -induced mPTP opening was assessed by the use of a potentiometric method.

RESULTS

Rosuvastatin significantly reduced myocardial infarct size and improved cardiac function at 5 and 10 nmol/L. Protection disappeared at higher concentration and reverted to increased damage at 50 nmol/L. At 5 nmol/L, rosuvastatin increased the phosphorylation of protein kinase B (Akt) and GSK-3β, concomitant with a higher Ca2+ load required to open the mPTP. Rosuvastatin postconditioning also significantly increased superoxide dismutase activity and reduced malondialdehyde and radical oxygen species level. LY294002, phosphatidylinositol-3-kinase (PI3K) inhibitors, abolished these protective effects of rosuvastatin postconditioning.

CONCLUSION

Rosuvastatin prevents myocardial ischemia-reperfusion injury by inducing phosphorylation of PI3K-Akt and GSK-3β, preventing oxidative stress and subsequent inhibition of mPTP opening.

Authors+Show Affiliations

Department of Cardiology, Tianjin Medical University, Tianjin Chest Hospital, Tianjin, China.Department of Diagnostic Ultrasound, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China.Department of Cardiology, Tianjin Medical University, Tianjin Chest Hospital, Tianjin, China.Department of Cardiology, Tianjin Medical University, Tianjin Chest Hospital, Tianjin, China.Department of Cardiology, Tianjin Medical University, Tianjin Chest Hospital, Tianjin, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27580017

Citation

Liu, Chun-Wei, et al. "Rosuvastatin Postconditioning Protects Isolated Hearts Against Ischemia-reperfusion Injury: the Role of Radical Oxygen Species, PI3K-Akt-GSK-3β Pathway, and Mitochondrial Permeability Transition Pore." Cardiovascular Therapeutics, vol. 35, no. 1, 2017, pp. 3-9.
Liu CW, Yang F, Cheng SZ, et al. Rosuvastatin postconditioning protects isolated hearts against ischemia-reperfusion injury: The role of radical oxygen species, PI3K-Akt-GSK-3β pathway, and mitochondrial permeability transition pore. Cardiovasc Ther. 2017;35(1):3-9.
Liu, C. W., Yang, F., Cheng, S. Z., Liu, Y., Wan, L. H., & Cong, H. L. (2017). Rosuvastatin postconditioning protects isolated hearts against ischemia-reperfusion injury: The role of radical oxygen species, PI3K-Akt-GSK-3β pathway, and mitochondrial permeability transition pore. Cardiovascular Therapeutics, 35(1), 3-9. https://doi.org/10.1111/1755-5922.12225
Liu CW, et al. Rosuvastatin Postconditioning Protects Isolated Hearts Against Ischemia-reperfusion Injury: the Role of Radical Oxygen Species, PI3K-Akt-GSK-3β Pathway, and Mitochondrial Permeability Transition Pore. Cardiovasc Ther. 2017;35(1):3-9. PubMed PMID: 27580017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rosuvastatin postconditioning protects isolated hearts against ischemia-reperfusion injury: The role of radical oxygen species, PI3K-Akt-GSK-3β pathway, and mitochondrial permeability transition pore. AU - Liu,Chun-Wei, AU - Yang,Fan, AU - Cheng,Shi-Zhao, AU - Liu,Yue, AU - Wan,Liang-Hui, AU - Cong,Hong-Liang, PY - 2015/09/27/received PY - 2016/05/04/revised PY - 2016/08/26/accepted PY - 2016/9/1/pubmed PY - 2017/2/14/medline PY - 2016/9/1/entrez KW - ROS KW - GSK-3β KW - MPTP opening KW - PI3K-Akt KW - Rosuvastatin SP - 3 EP - 9 JF - Cardiovascular therapeutics JO - Cardiovasc Ther VL - 35 IS - 1 N2 - AIMS: Glycogen synthase kinase-3β (GSK-3β) and mitochondrial permeability transition pore (mPTP) play an important role in myocardial ischemia-reperfusion injury. The aim of this study was to investigate whether postconditioning with rosuvastatin is able to reduce myocardial ischemia-reperfusion injury and clarify the potential mechanisms. METHODS: Isolated rat hearts underwent 30 minutes of ischemia and 60 minutes of reperfusion in the presence or absence of rosuvastatin (1-50 nmol/L). The activity of signaling pathway was determined by Western blot analysis, and Ca2+ -induced mPTP opening was assessed by the use of a potentiometric method. RESULTS: Rosuvastatin significantly reduced myocardial infarct size and improved cardiac function at 5 and 10 nmol/L. Protection disappeared at higher concentration and reverted to increased damage at 50 nmol/L. At 5 nmol/L, rosuvastatin increased the phosphorylation of protein kinase B (Akt) and GSK-3β, concomitant with a higher Ca2+ load required to open the mPTP. Rosuvastatin postconditioning also significantly increased superoxide dismutase activity and reduced malondialdehyde and radical oxygen species level. LY294002, phosphatidylinositol-3-kinase (PI3K) inhibitors, abolished these protective effects of rosuvastatin postconditioning. CONCLUSION: Rosuvastatin prevents myocardial ischemia-reperfusion injury by inducing phosphorylation of PI3K-Akt and GSK-3β, preventing oxidative stress and subsequent inhibition of mPTP opening. SN - 1755-5922 UR - https://www.unboundmedicine.com/medline/citation/27580017/Rosuvastatin_postconditioning_protects_isolated_hearts_against_ischemia_reperfusion_injury:_The_role_of_radical_oxygen_species_PI3K_Akt_GSK_3β_pathway_and_mitochondrial_permeability_transition_pore_ L2 - https://doi.org/10.1111/1755-5922.12225 DB - PRIME DP - Unbound Medicine ER -