See Hoe Louise E, May Lauren T, Headrick John P, Peart Jason N
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Chermside, Queensland, Australia.
Br J Pharmacol. 2016 Oct;173(20):2966-91. doi: 10.1111/bph.13552. Epub 2016 Sep 9.
Disruption of the sarcolemmal membrane is a defining feature of oncotic death in cardiac ischaemia-reperfusion (I-R), and its molecular makeup not only fundamentally governs this process but also affects multiple determinants of both myocardial I-R injury and responsiveness to cardioprotective stimuli. Beyond the influences of membrane lipids on the cytoprotective (and death) receptors intimately embedded within this bilayer, myocardial ionic homeostasis, substrate metabolism, intercellular communication and electrical conduction are all sensitive to sarcolemmal makeup, and critical to outcomes from I-R. As will be outlined in this review, these crucial sarcolemmal dependencies may underlie not only the negative effects of age and common co-morbidities on myocardial ischaemic tolerance but also the on-going challenge of implementing efficacious cardioprotection in patients suffering accidental or surgically induced I-R. We review evidence for the involvement of sarcolemmal makeup changes in the impairment of stress-resistance and cardioprotection observed with ageing and highly prevalent co-morbid conditions including diabetes and hypercholesterolaemia. A greater understanding of membrane changes with age/disease, and the inter-dependences of ischaemic tolerance and cardioprotection on sarcolemmal makeup, can facilitate the development of strategies to preserve membrane integrity and cell viability, and advance the challenging goal of implementing efficacious 'cardioprotection' in clinically relevant patient cohorts. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.
肌膜破裂是心脏缺血再灌注（I-R）中胀亡的一个决定性特征，其分子组成不仅从根本上控制这一过程，还影响心肌I-R损伤的多个决定因素以及对心脏保护刺激的反应性。除了膜脂对紧密嵌入该双层膜中的细胞保护（和死亡）受体的影响外，心肌离子稳态、底物代谢、细胞间通讯和电传导都对肌膜组成敏感，并且对I-R的结果至关重要。正如本综述将要概述的，这些关键的肌膜依赖性可能不仅是年龄和常见合并症对心肌缺血耐受性产生负面影响的基础，也是在意外或手术诱导的I-R患者中实施有效心脏保护面临持续挑战的原因。我们综述了有关肌膜组成变化参与衰老以及包括糖尿病和高胆固醇血症在内的高度普遍合并症所观察到的应激抵抗受损和心脏保护受损的证据。更深入地了解随着年龄/疾病变化的膜改变，以及缺血耐受性和心脏保护对肌膜组成的相互依赖性，有助于制定保护膜完整性和细胞活力的策略，并推动在临床相关患者群体中实施有效“心脏保护”这一具有挑战性目标的实现。相关文章 本文是关于G蛋白偶联受体分子药理学主题部分的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc。
