The adult mammalian heart has limited endogenous regenerative capacity and heals through the activation of inflammatory and fibrogenic cascades that ultimately result in the formation of a scar. After infarction, massive cardiomyocyte death releases a broad range of damage-associated molecular patterns that initiate both myocardial and systemic inflammatory responses. TLRs (toll-like receptors) and NLRs (NOD-like receptors) recognize damage-associated molecular patterns (DAMPs) and transduce downstream proinflammatory signals, leading to upregulation of cytokines (such as interleukin-1, TNF-α [tumor necrosis factor-α], and interleukin-6) and chemokines (such as CCL2 [CC chemokine ligand 2]) and recruitment of neutrophils, monocytes, and lymphocytes. Expansion and diversification of cardiac macrophages in the infarcted heart play a major role in the clearance of the infarct from dead cells and the subsequent stimulation of reparative pathways. Efferocytosis triggers the induction and release of anti-inflammatory mediators that restrain the inflammatory reaction and set the stage for the activation of reparative fibroblasts and vascular cells. Growth factor-mediated pathways, neurohumoral cascades, and matricellular proteins deposited in the provisional matrix stimulate fibroblast activation and proliferation and myofibroblast conversion. Deposition of a well-organized collagen-based extracellular matrix network protects the heart from catastrophic rupture and attenuates ventricular dilation. Scar maturation requires stimulation of endogenous signals that inhibit fibroblast activity and prevent excessive fibrosis. Moreover, in the mature scar, infarct neovessels acquire a mural cell coat that contributes to the stabilization of the microvascular network. Excessive, prolonged, or dysregulated inflammatory or fibrogenic cascades accentuate adverse remodeling and dysfunction. Moreover, inflammatory leukocytes and fibroblasts can contribute to arrhythmogenesis. Inflammatory and fibrogenic pathways may be promising therapeutic targets to attenuate heart failure progression and inhibit arrhythmia generation in patients surviving myocardial infarction.

中文翻译：

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梗塞心脏的修复：细胞效应器、分子机制和治疗机会。


成年哺乳动物心脏的内源性再生能力有限，并通过炎症和纤维化级联的激活而愈合，最终导致疤痕的形成。梗塞后，大量心肌细胞死亡，释放出多种与损伤相关的分子模式，引发心肌和全身炎症反应。 TLR（Toll 样受体）和 NLR（NOD 样受体）识别损伤相关分子模式 (DAMP) 并转导下游促炎信号，导致细胞因子（如白介素-1、TNF-α [肿瘤坏死因子- α] 和白细胞介素 6）和趋化因子（例如 CCL2 [CC 趋化因子配体 2]）以及中性粒细胞、单核细胞和淋巴细胞的募集。梗塞心脏中心脏巨噬细胞的扩张和多样化在清除梗塞死细胞以及随后刺激修复途径方面发挥着重要作用。胞吞作用触发抗炎介质的诱导和释放，抑制炎症反应并为修复性成纤维细胞和血管细胞的激活奠定基础。生长因子介导的途径、神经体液级联和沉积在临时基质中的基质细胞蛋白刺激成纤维细胞活化和增殖以及肌成纤维细胞转化。组织良好的基于​​胶原蛋白的细胞外基质网络的沉积可保护心脏免遭灾难性破裂并减弱心室扩张。疤痕成熟需要刺激内源性信号，抑制成纤维细胞活性并防止过度纤维化。此外，在成熟的疤痕中，梗塞新生血管获得了有助于微血管网络稳定的壁细胞外套。 过度、长期或失调的炎症或纤维化级联会加剧不利的重塑和功能障碍。此外，炎症白细胞和成纤维细胞可导致心律失常的发生。炎症和纤维化途径可能是有希望的治疗靶点，可减轻心肌梗死患者心力衰竭的进展并抑制心律失常的发生。