Regulation of the inflammatory response in cardiac repair.
Regulation of the inflammatory response in cardiac repair.
复制标题
DOI：
10.1161/circresaha.111.243162
复制
发表时间：
2012-01-06
影响因子：
20.1
通讯作者：
Frangogiannis NG
中科院分区：
文献类型：
--
作者：
Frangogiannis NG
心肌坏死引发炎症反应，清除伤口上的死细胞和基质碎片，同时激活疤痕形成所需的修复途径。越来越多的证据表明，心肌梗死后炎症反应的加重、延长或扩大会导致心肌梗死后更严重的重构和功能障碍。这篇综述文章讨论了细胞效应物和内源性分子信号在梗死心脏炎症反应的抑制和遏制中的作用。凋亡中性粒细胞的清除、抑制性单核细胞亚群和调节性T细胞的募集、巨噬细胞分化和周细胞/内皮细胞相互作用可能在抑制梗死后炎症中发挥积极作用。多种分子信号可能参与抑制炎症级联反应。Toll样受体信号传导的负调节、细胞因子应答的下调和趋化因子信号的终止可以通过多种抑制性途径的协同作用介导，所述多种抑制性途径防止损伤的扩展并防止不良重塑。可溶性内源性拮抗剂、诱饵受体的表达和生物活性分子的翻译后加工可能限制细胞因子和趋化因子的作用。白细胞介素（IL）-10、转化生长因子（TGF）-β家族成员和促消退脂质介质（如脂氧素、消退素和保护素）可抑制促炎信号传导。在患有心肌梗死的人类患者中，炎症的抑制缺陷和消退受损可能是重塑发病机制和进展为心力衰竭的重要机制。需要了解梗死心脏中的抑制性和促消退信号，并识别患有不受控制的梗死后炎症和心脏修复缺陷的患者，以设计新的治疗策略。
Myocardial necrosis triggers an inflammatory reaction that clears the wound from dead cells and matrix debris, while activating reparative pathways necessary for scar formation. A growing body of evidence suggests that accentuation, prolongation or expansion of the post-infarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction. This review manuscript discusses the cellular effectors and endogenous molecular signals implicated in suppression and containment of the inflammatory response in the infarcted heart. Clearance of apoptotic neutrophils, recruitment of inhibitory monocyte subsets and regulatory T cells, macrophage differentiation and pericyte/endothelial interactions may play an active role in restraining post-infarction inflammation. Multiple molecular signals may be involved in suppressing the inflammatory cascade. Negative regulation of toll-like receptor signaling, downmodulation of cytokine responses and termination of chemokine signals may be mediated through the concerted action of multiple suppressive pathways that prevent extension of injury and protect from adverse remodeling. Expression of soluble endogenous antagonists, decoy receptors, and post-translational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin (IL)-10, members of the Transforming Growth Factor (TGF)-β family, and pro-resolving lipid mediators (such as lipoxins, resolvins and protectins) may suppress pro-inflammatory signaling. In human patients with myocardial infarction, defective suppression and impaired resolution of inflammation may be important mechanisms in the pathogenesis of remodeling and in progression to heart failure. Understanding of inhibitory and pro-resolving signals in the infarcted heart and identification of patients with uncontrolled post-infarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.