Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium.
Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium.
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DOI：
10.1016/j.pharmthera.2014.03.009
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发表时间：
2014-09
影响因子：
13.5
通讯作者：
Yellon, Derek M.
中科院分区：
文献类型：
--
作者：
Bromage, Daniel I.;Davidson, Sean M.;Yellon, Derek M.
减轻与ST段抬高心肌梗死相关的心肌损伤是改善冠心病全球负担的关键。趋化因子基质细胞衍生因子1 α（SDF-1 α）在这方面具有双重潜在益处。首先，SDF-1 α在急性心肌梗死（AMI）的实验和临床研究中上调，并调节干细胞向损伤部位的迁移。AMI后向心肌输送SDF-1 α与动物模型中干细胞归巢、血管生成和左心室功能的改善以及人类心力衰竭和生活质量的改善相关。其次，SDF-1 α可能在远程缺血条件（RIC）中发挥作用，即对远离心脏的器官或组织进行非致死性缺血再灌注保护心肌免受致死性缺血再灌注损伤（IRI）的现象。SDF-1 α在RIC大鼠血清中升高，并在离体研究中保护心肌IRI。尽管存在这些潜在的多效性作用，但SDF-1 α的局限性是其血浆半衰期较短，这是由于其被二肽基肽酶-4（DPP-4）裂解所致。然而，DPP-4抑制剂通过防止SDF-1 α降解延长其半衰期，并且还可保护免受致死性IRI。总之，SDF-1可能提供心肌的“双管齐下”防御：急性保护其免受IRI，同时通过将干细胞募集到损伤部位来刺激修复。在这篇文章中，我们检查了SDF-1 α的急性和慢性心脏保护作用的证据，并讨论了DPP-4抑制剂在临床环境中保护致死性组织损伤的潜在治疗方法。
Alleviating myocardial injury associated with ST elevation myocardial infarction is central to improving the global burden of coronary heart disease. The chemokine stromal cell-derived factor 1α (SDF-1α) has dual potential benefit in this regard. Firstly, SDF-1α is up-regulated in experimental and clinical studies of acute myocardial infarction (AMI) and regulates stem cell migration to sites of injury. SDF-1α delivery to the myocardium after AMI is associated with improved stem cell homing, angiogenesis, and left ventricular function in animal models, and improvements in heart failure and quality of life in humans. Secondly, SDF-1α may have a role in remote ischaemic conditioning (RIC), the phenomenon whereby non-lethal ischaemia–reperfusion applied to an organ or tissue remote from the heart protects the myocardium from lethal ischaemia–reperfusion injury (IRI). SDF-1α is increased in the serum of rats subjected to RIC and protects against myocardial IRI in ex vivo studies. Despite these potential pleiotropic effects, a limitation of SDF-1α is its short plasma half-life due to cleavage by dipeptidyl peptidase-4 (DPP-4). However, DPP-4 inhibitors increase the half-life of SDF-1α by preventing its degradation and are also protective against lethal IRI. In summary, SDF-1 potentially delivers a ‘two-pronged’ defence of the myocardium: acutely protecting it from IRI while simultaneously stimulating repair by recruiting stem cells to the site of injury. In this article we examine the evidence for acute and chronic cardioprotective roles of SDF-1α and discuss potential therapeutic manipulations of this mechanism with DPP-4 inhibitors to protect against lethal tissue injury in the clinical setting.
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