Department of Cardiology, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China (mainland).
Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China (mainland).
Med Sci Monit. 2018 Apr 30;24:2661-2667. doi: 10.12659/MSM.907578.
Reperfusion after myocardial ischemia can induce cardiomyocyte death, known as myocardial reperfusion injury. The pathophysiology of the process of reperfusion suggests the confluence multiple pathways. Recent studies have focused on the inflammatory response, which is considered to be the main mechanism during the process of myocardial ischemia-reperfusion injury and can cause cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors gamma activated by endogenous ligands and exogenous ligand can decrease the inflammatory response in cardiomyocytes. Thiazolidinediones are synthetic, high-affinity, selective ligands for peroxisome proliferator-activated receptors gamma, and can inhibit the inflammatory response, decrease myocardial infarct size, and protect cardiac function. However, thiazolidinediones, including rosiglitazone and pioglitazone, can also contribute to adverse cardiovascular events such as congestive heart failure. Therefore, there are some limitations to the use of thiazolidinediones. Most endogenous ligands were of low affinity until hexadecyl azelaoyl phosphatidylcholine was identified as a high-affinity ligand and agonist for peroxisome proliferator-activated receptors gamma. Hexadecyl azelaoyl phosphatidylcholine binds recombinant peroxisome proliferator-activated receptors with an affinity (Kd(app) ≈40 nM) which is equivalent to rosiglitazone. Therefore, hexadecyl azelaoyl phosphatidylcholine is a specific peroxisome proliferator-activated receptors gamma agonist. Given these findings, we hypothesized that the use of hexadecyl azelaoyl phosphatidylcholine can activate the peroxisome proliferator-activated receptors gamma signal pathways and prevent the inflammatory response process of myocardial ischemia-reperfusion injury, with reduced cardiomyocyte apoptosis and death.
心肌缺血再灌注可诱导心肌细胞死亡，称为心肌再灌注损伤。再灌注过程的病理生理学表明，多个途径汇聚在一起。最近的研究集中在炎症反应上，它被认为是心肌缺血再灌注损伤过程中的主要机制，并可导致心肌细胞凋亡。内源性配体和外源性配体激活的过氧化物酶体增殖物激活受体γ可降低心肌细胞中的炎症反应。噻唑烷二酮类是过氧化物酶体增殖物激活受体γ的合成、高亲和力、选择性配体，可抑制炎症反应，减少心肌梗死面积，保护心功能。然而，噻唑烷二酮类，包括罗格列酮和吡格列酮，也可能导致充血性心力衰竭等不良心血管事件。因此，噻唑烷二酮类的应用存在一些局限性。大多数内源性配体的亲和力较低，直到十六烷基壬酰基磷脂酰胆碱被确定为过氧化物酶体增殖物激活受体γ的高亲和力配体和激动剂。十六烷基壬酰基磷脂酰胆碱与重组过氧化物酶体增殖物激活受体的亲和力（Kd(app)≈40 nM）与罗格列酮相当。因此，十六烷基壬酰基磷脂酰胆碱是一种特异性过氧化物酶体增殖物激活受体γ激动剂。基于这些发现，我们假设使用十六烷基壬酰基磷脂酰胆碱可以激活过氧化物酶体增殖物激活受体γ信号通路，防止心肌缺血再灌注损伤的炎症反应过程，减少心肌细胞凋亡和死亡。
