The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, 67 Chenies Mews, London WC1E 6HX, UK.
Cardiovasc Res. 2018 Mar 1;114(3):358-367. doi: 10.1093/cvr/cvx203.
Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilize and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium. These effects have beneficial effects on infarct size, and left ventricular remodelling and function. However, the timing of endogenous SDF-1α release and CXCR4 upregulation may not be optimal. Furthermore, current ELISA-based assays cannot distinguish between active SDF-1α, and SDF-1α inactivated by dipeptidyl peptidase 4 (DPP4). Current therapeutic approaches aim to recruit the SDF-1α-CXCR4 pathway or prolong SDF-1α life-time by preventing its cleavage by DPP4. This review assesses the evidence supporting these approaches and proposes SDF-1α as an important confounder in recent studies of DPP4 inhibitors.
心力衰竭的发病率迅速上升，将重新绘制全球心血管健康的格局。减轻和修复与心肌梗死（MI）相关的心脏损伤是改善这一负担的关键。归巢信号动员和招募干细胞到缺血性心肌，在那里它们发挥有益的旁分泌作用。趋化因子 SDF-1α及其相关受体 CXCR4 在 MI 后上调，在这种情况下似乎很重要。CXCR4 的激活促进心肌细胞存活和干细胞向梗死心肌迁移。这些作用对梗死面积、左心室重构和功能有有益的影响。然而，内源性 SDF-1α释放和 CXCR4 上调的时间可能不是最佳的。此外，目前基于 ELISA 的检测方法无法区分活性 SDF-1α和二肽基肽酶 4（DPP4）失活的 SDF-1α。目前的治疗方法旨在通过阻止 DPP4 切割来招募 SDF-1α-CXCR4 途径或延长 SDF-1α 的寿命。这篇综述评估了支持这些方法的证据，并提出 SDF-1α 是最近 DPP4 抑制剂研究中的一个重要混杂因素。
