Mitsugumin-53: potential biomarker and therapeutic for myocardial ischemic injury?
Mitsugumin-53: potential biomarker and therapeutic for myocardial ischemic injury?
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Mitsugumin-53：心肌缺血性损伤的潜在生物标志物和治疗方法？
DOI：
10.1016/j.yjmcc.2015.01.023
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发表时间：
2015
影响因子：
5
通讯作者：
Kohr,MarkJ
中科院分区：
文献类型：
--
作者：
Kohr,MarkJ
缺血-再灌注损伤是许多病理情况的基础，包括缺血性心脏病，这是世界范围内的主要死亡原因[1]。心肌缺血-再灌注损伤是由心脏某一区域的血液供应中断引起的，最常见的原因是急性冠脉闭塞。当缺血区再灌流时，也会发生显著的损伤，因为活性氧物种的形成[2]会导致额外的心肌损伤，它可以通过激活心肌细胞中的促凋亡和/或坏死信号通路来触发细胞死亡[3]。细胞死亡的问题在心脏中至关重要，因为心肌细胞是终末分化的，除了心脏前体细胞，心肌在内源性再生能力方面非常有限[4]。心脏保护干预在减少心肌缺血-再灌注损伤的有害影响方面有很大的希望[5]，并且已经被证明在动物模型中减少收缩功能障碍、心律失常的发生和细胞死亡[6]、[7]、[8]、[9]。1986年，Murry和Remer最初描述了一种强大的心脏保护现象，称为缺血预适应(IPC)，通过短暂暴露于缺血和再灌注期，可以保护心脏免受更长时间的缺血性损伤[6]。然而，IPC必须在缺血发作之前进行，从而限制了临床适用性。自从最初发现IPC以来，已经描述了具有更大临床适用性的其他保护机制，包括缺血后处理[10]，以及腺苷[11]、环孢素[12]和一氧化氮[13]等药理药物。从机制上讲，仍有许多有待确定的因素，但这些干预措施被认为集中在类似的细胞保护信号通路上，其中可能包括再灌注损伤挽救激酶(Risk)通路，该通路主要由磷脂酰肌醇3-激酶/Akt、ERK1/2和糖原合成酶激酶3β[14]组成。尽管致力于阐明心脏保护信号通路的研究已经进行了近40年，但很少有实验发现成功地转化为有效的治疗方法，目前，唯一公认的持续缩小人类心肌梗死范围的干预措施是早期冠状动脉再灌注，它仍然有可能导致如上所述的额外心肌损伤。刘等人[15]最近的研究为使用重组蛋白，即膜修复蛋白Mitsugumin-53治疗缺血性心脏病的潜在治疗方法带来了新的视角。
Ischemia-reperfusion injury underlies many pathological conditions, including ischemic heart disease, which is a major cause of death worldwide [1]. Myocardial ischemia-reperfusion injury results from an interruption in the blood supply to a region of the heart and is most often the result of acute coronary occlusion. Significant injury also occurs upon reperfusion of the ischemic region, as additional myocardial damage results from the formation of reactive oxygen species [2], which can trigger cell death by activating pro-apoptotic and/or necrotic signaling pathways in cardiomyocytes [3]. The issue of cell death is of paramount importance in the heart since cardiomyocytes are terminally differentiated, and aside from cardiac progenitor cells, the myocardium is very limited with regard to endogenous regenerative capabilities [4]. Cardioprotective interventions hold great promise for lessening the detrimental effects of myocardial ischemia-reperfusion injury [5] and have been shown to reduce contractile dysfunction, arrhythmogenesis and cell death in animal models [6],[7],[8],[9]. In 1986, Murry and Reimer originally described the powerful cardioprotective phenomena known as ischemic preconditioning (IPC), whereby brief exposure to periods of ischemia and reperfusion serves to protect the heart against a more prolonged ischemic insult [6]. However, IPC must be performed prior to the onset of ischemia, thereby limiting clinical applicability. Since the initial discovery of IPC, additional protective mechanisms with greater clinical applicability have been described, including ischemic postconditioning [10], and pharmacologic agents such as adenosine [11], cyclosporine [12], and nitric oxide [13]. Mechanistically, there is much that remains to be defined, but these interventions are thought to converge on similar cytoprotective signaling pathways that may include the reperfusion injury salvage kinase (RISK) pathway, which is comprised primarily of phosphoinositide 3-kinase/Akt, ERK1/2, and glycogen synthase kinase 3 beta [14]. Although research devoted to the elucidation of cardioprotective signaling pathways has been ongoing for nearly 40 years, few experimental discoveries have translated successfully into effective therapeutics, and currently, the only established intervention that consistently reduces infarct size in humans is early coronary artery reperfusion, which still has the potential to cause additional myocardial injury as mentioned above. The recent study from Liu et al.[15] brings a fresh perspective on potential therapeutic approaches for the treatment of ischemic heart disease with the use of recombinant protein, namely, the membrane repair protein mitsugumin-53.