Rana A, Goyal N, Ahlawat A, Jamwal S, Reddy B V K, Sharma S
Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India.
Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India
Perfusion. 2015 Mar;30(2):94-105. doi: 10.1177/0267659114536760. Epub 2014 Jun 19.
Myocardial infarction is a pathological state which occurs due to severe abrogation of the blood supply (ischemia) to a part of heart, which can cause myocardial damage. The short intermittent cycles of sub-lethal ischemia and reperfusion has shown to improve the tolerance of the myocardium against subsequent prolonged ischemia/reperfusion (I/R)-induced injury, which is known as ischemic preconditioning (IPC). Although, IPC-induced cardioprotection is well demonstrated in various species, including human beings, accumulated evidence clearly suggests critical abrogation of the beneficial effects of IPC in diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. Various factors are involved in the attenuation of the cardioprotective effect of preconditioning, such as the reduced release of calcitonin gene-related peptide (CGRP), the over-expression of glycogen synthase kinase-3β (GSK-3β) and phosphatase and tensin homolog (PTEN), impairment of mito-KATP channels, the consequent opening of mitochondrial permeability transition pore (MPTP), etc. In this review, we have critically discussed the various signaling pathways involved in abrogated preconditioning in chronic diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. We have also focused on the involvement of PTEN in abrogated preconditioning and the significance of PTEN inhibitors.
心肌梗死是一种病理状态，它是由于心脏某一部分的血液供应严重中断（缺血）而发生的，这会导致心肌损伤。亚致死性缺血和再灌注的短间歇性周期已被证明可提高心肌对随后长时间缺血/再灌注（I/R）诱导损伤的耐受性，这被称为缺血预处理（IPC）。尽管IPC诱导的心脏保护作用在包括人类在内的各种物种中都得到了充分证明，但越来越多的证据清楚地表明，在糖尿病、高脂血症和高同型半胱氨酸血症中，IPC的有益作用会受到严重破坏。预处理心脏保护作用的减弱涉及多种因素，如降钙素基因相关肽（CGRP）释放减少、糖原合酶激酶-3β（GSK-3β）和磷酸酶及张力蛋白同源物（PTEN）过度表达、线粒体ATP敏感性钾通道（mito-KATP）受损、随后线粒体通透性转换孔（MPTP）开放等。在本综述中，我们批判性地讨论了慢性糖尿病、高脂血症和高同型半胱氨酸血症中预处理作用被破坏所涉及的各种信号通路。我们还重点关注了PTEN在预处理作用被破坏中的作用以及PTEN抑制剂的意义。
