Cheng Bill, Chen H C, Chou I W, Tang Tony W H, Hsieh Patrick C H
Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Sec. 2, Nankang District, Taipei, 115, Taiwan.
Graduate Institute of Life Sciences, National Defence Medical Center, Taipei, 114, Taiwan.
J Biomed Sci. 2017 Jan 13;24(1):7. doi: 10.1186/s12929-017-0315-2.
Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction. Monocytes would transdifferentiate into macrophages after transmigrating into the infarct area. Both neutrophils and monocytes-derived macrophages are known to release proteases and cytokines that are detrimental to the surviving cardiomyocytes. Paradoxically, these inflammatory cells also play critical roles in repairing the injured myocardium. Depletion of either neutrophils or monocytes do not improve overall cardiac function after myocardial infarction. Instead, the left ventricular function is further impaired and cardiac fibrosis persists. Moreover, the inflammatory microenvironment created by the infiltrated neutrophils and monocytes-derived macrophages is essential for the recruitment of cardiac progenitor cells. Recent studies also suggest that treatment with anti-inflammatory drugs may cause cardiac dysfunction after injury. Indeed, clinical studies have shown that traditional ant-inflammatory strategies are ineffective to improve cardiac function after infarction. Thus, the focus should be on how to harness these inflammatory events to either improve the efficacy of the delivered drugs or to favor the recruitment of cardiac progenitor cells.
许多人认为心脏炎症是心肌梗死后延长心脏病理状态的主要驱动力。心脏缺血性损伤后，中性粒细胞是在最初24小时内被招募到缺血心肌的首批固有免疫细胞。一旦它们浸润到受损心肌，中性粒细胞就会分泌促进心脏重塑的蛋白酶和增强单核细胞从脾脏募集的趋化因子，单核细胞募集在心肌梗死后72小时达到峰值。单核细胞迁移到梗死区域后会转分化为巨噬细胞。已知中性粒细胞和单核细胞衍生的巨噬细胞都会释放对存活心肌细胞有害的蛋白酶和细胞因子。矛盾的是，这些炎症细胞在修复受损心肌方面也起着关键作用。心肌梗死后，清除中性粒细胞或单核细胞均不能改善整体心脏功能。相反，左心室功能会进一步受损，心脏纤维化持续存在。此外，浸润的中性粒细胞和单核细胞衍生的巨噬细胞所创造的炎症微环境对于心脏祖细胞的募集至关重要。最近的研究还表明，使用抗炎药物治疗可能会在损伤后导致心脏功能障碍。事实上，临床研究表明，传统的抗炎策略对改善梗死后心脏功能无效。因此，重点应放在如何利用这些炎症事件来提高所递送药物的疗效或促进心脏祖细胞的募集上。
