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尿皮质素在缺血性心脏保护和不良心脏重构中的作用。

Urocortin Role in Ischemia Cardioprotection and the Adverse Cardiac Remodeling.

机构信息

Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Rocío/University of Seville/CSIC, 41013 Seville, Spain.

Department of Medical Physiology and Biophysics, University of Seville, 41009 Seville, Spain.

出版信息

Int J Mol Sci. 2021 Nov 9;22(22):12115. doi: 10.3390/ijms222212115.

Abstract

Despite the considerable progress in strategies of myocardial protection, ischemic heart diseases (IHD) and consequent heart failure (HF) remain the main cause of mortality worldwide. Several procedures are used routinely to guarantee the prompt and successful reestablishment of blood flow to preserve the myocardial viability of infarcted hearts from ischemia injuries. However, ischemic heart reperfusion/revascularization triggers additional damages that occur when oxygen-rich blood re-enters the vulnerable myocardial tissue, which is a phenomenon known as ischemia and reperfusion (I/R) syndrome. Complications of I/R injuries provoke the adverse cardiac remodeling, involving inflammation, mishandling of Ca homeostasis, apoptotic genes activation, cardiac myocytes loss, etc., which often progress toward HF. Therefore, there is an urgent need to develop new cardioprotective therapies for IHD and HF. Compelling evidence from animal studies and pilot clinical trials in HF patients suggest that urocortin (Ucn) isoforms, which are peptides associated with stress and belonging to the corticotropin releasing factor family, have promising potential to improve cardiovascular functions by targeting many signaling pathways at different molecular levels. This review highlights the current knowledge on the role of urocortin isoforms in cardioprotection, focusing on its acute and long-term effects.

摘要

尽管在心肌保护策略方面取得了相当大的进展,但缺血性心脏病 (IHD) 和由此导致的心力衰竭 (HF) 仍然是全球死亡的主要原因。有几种常规程序用于保证迅速和成功地恢复血流,以保护缺血性心脏病患者的心肌活力免受缺血损伤。然而,缺血性心脏再灌注/再血管化会引发更多的损伤,当富含氧气的血液重新进入脆弱的心肌组织时,就会发生这种现象,称为缺血再灌注 (I/R) 综合征。I/R 损伤的并发症会引起不良的心脏重构,涉及炎症、钙稳态失调、凋亡基因激活、心肌细胞损失等,这些通常会导致 HF。因此,迫切需要为 IHD 和 HF 开发新的心脏保护疗法。动物研究和 HF 患者的初步临床试验提供了有力的证据表明,尿皮质素 (Ucn) 同种型是与应激相关的肽,属于促肾上腺皮质素释放因子家族,通过靶向不同分子水平的许多信号通路,具有改善心血管功能的巨大潜力。本文综述了 Ucn 同种型在心脏保护中的作用的最新知识,重点介绍了其急性和长期作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/638f/8622004/c2f691bbfe15/ijms-22-12115-g001.jpg

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