Juan Zhang1, Xiao-Bo Liu2, Chao Cheng1, Dong-Ling Xu1, Qing-Hua Lu1, Xiao-Ping Ji3. 1. Department of Cardiology, The Second Hospital of Shandong University Jinan, Shandong Province, China. 2. Shandong Blood Center Jinan, Shandong Province, China. 3. The Key Laboratory of Cardiovascular Remodeling and Function Research of Chinese Ministry of Education and Public Health, Shandong University Qilu Hospital Jinan, Shandong Province, China.
Abstract
UNLABELLED: We and others have reported that Rho-kinase plays an important role in the pathogenesis of heart ischemia/reperfusion (I/R) injury. Studies also have demonstrated that the activation of Rho-kinase was reversed in ischemic preconditioning (IPC). This study aimed to explain the mechanism of Rho-kinase-mediated cardiomyocyte apoptosis increased in I/R and reversed in IPC. MATERIALS AND METHODS: Studies were performed with female Wistar rats. The I/R rats were created by ligating the left anterior descending branch (LAD) for 30 min and releasing the ligature for 180 min. The IPC rats underwent IPC (two cycles of 5 min ligation of the LAD and 5 min reflow) before I/R. RESULTS: Ischemia followed by reperfusion caused a significant increase in Rho-kinase and a decrease in Akt phosphorylation. Administration of fasudil, an inhibitor of Rho-kinase, decreased myocardial infarction size and cardiomyocyte apoptosis and increased Akt activation. IPC also caused the reduced Rho-kinase activity and cardiomyocyte apoptosis and a significant increase in Akt activity (P<0.05 vs I/R). CONCLUSION: Rho-kinase inhibition by IPC leads to reduced cardiomyocyte apoptosis may be mediated by activation of PI3-kinase/Akt.
UNLABELLED: We and others have reported that Rho-kinase plays an important role in the pathogenesis of heart ischemia/reperfusion (I/R) injury. Studies also have demonstrated that the activation of Rho-kinase was reversed in ischemic preconditioning (IPC). This study aimed to explain the mechanism of Rho-kinase-mediated cardiomyocyte apoptosis increased in I/R and reversed in IPC. MATERIALS AND METHODS: Studies were performed with female Wistar rats. The I/R rats were created by ligating the left anterior descending branch (LAD) for 30 min and releasing the ligature for 180 min. The IPC rats underwent IPC (two cycles of 5 min ligation of the LAD and 5 min reflow) before I/R. RESULTS:Ischemia followed by reperfusion caused a significant increase in Rho-kinase and a decrease in Akt phosphorylation. Administration of fasudil, an inhibitor of Rho-kinase, decreased myocardial infarction size and cardiomyocyte apoptosis and increased Akt activation. IPC also caused the reduced Rho-kinase activity and cardiomyocyte apoptosis and a significant increase in Akt activity (P<0.05 vs I/R). CONCLUSION: Rho-kinase inhibition by IPC leads to reduced cardiomyocyte apoptosis may be mediated by activation of PI3-kinase/Akt.
Authors: Yi-Xin Wang; Valdeci da Cunha; Baby Martin-McNulty; Jon Vincelette; Weiwei Li; David F Choy; Meredith Halks-Miller; Mithra Mahmoudi; Miriam Schroeder; Anthony Johns; David R Light; William P Dole Journal: Eur J Pharmacol Date: 2005-04-11 Impact factor: 4.432
Authors: Shunsuke Miyahara; Alexander Jenke; Mariam Yazdanyar; Julia Kistner; Moritz Benjamin Immohr; Yukiharu Sugimura; Hug Aubin; Hiroyuki Kamiya; Yutaka Okita; Artur Lichtenberg; Payam Akhyari Journal: Asian Cardiovasc Thorac Ann Date: 2022-07-15