Frangogiannis Nikolaos G
Wilf Family Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY.
J Cardiovasc Pharmacol. 2014 Mar;63(3):185-95. doi: 10.1097/FJC.0000000000000003.
Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-like receptor/interleukin-1 signaling, resulting in the activation of the nuclear factor-κB system and induction of chemokines, cytokines, and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment, and resolution of the postinfarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction, and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury.
梗死心肌中缺血性心肌细胞的广泛坏死激活了固有免疫反应，引发强烈的炎症反应。死亡细胞和受损基质释放危险信号，激活补体级联反应并刺激Toll样受体/白细胞介素-1信号传导，导致核因子-κB系统激活，并诱导趋化因子、细胞因子和黏附分子。随后，中性粒细胞和单核细胞浸润梗死区域，清除死细胞和基质碎片，同时刺激修复途径。免疫系统除了在梗死心脏修复和瘢痕形成中发挥作用外，还参与梗死心室的不良重塑。过度活跃的免疫反应以及梗死灶后炎症反应抑制、局限和消退方面的缺陷，在实验模型中加剧了扩张性重塑，并且可能与心肌梗死后存活患者的心室扩张、收缩功能障碍和心力衰竭有关。针对炎症反应以减轻不良重塑的干预措施，对于那些对急性损伤表现出增强、延长或失调免疫反应的心肌梗死患者可能具有前景。
