Cardiovascular fibrosis refers to the scar tissue that develops in the injured heart and blood vessels from an aberrant wound healing response to organ injury or insult. Established fibrosis becomes a hallmark of chronic disease progression and a key contributor to tissue stiffness and dysfunction, which ultimately leads to heart failure. As wound healing and fibrotic responses to myocardial injury are multifactorial processes, current therapies that only target specific contributing factors to disease pathogenesis offer limited overall anti-fibrotic efficacy. As such, recent attention has turned to targeting the body's immune system, which orchestrates the wound healing response to tissue injury. This review focuses on the increasing body of work that has identified the NLRP3 inflammasome, a multiprotein oligomer complex responsible for activation of inflammatory responses via its production of IL-1β and IL-18, as an immune system-initiated facilitator of cardiovascular healing, but also an important contributor to tissue scarring following its persistent activation. The review summarises the factors that can elicit priming and activation of the inflammasome complex, how the activated inflammasome complex contributes to cardiovascular pathophysiology and fibrosis progression, and the molecular mechanisms involved from various cell culture and animal model studies that have utilised genetic deletion or pharmacological inhibition of specific components of the inflammasome. Finally, it outlines currently known and previously unrecognised cardiovascular receptors that may be pharmacologically targeted to ablate the contribution of the NLRP3 inflammasome to cardiovascular diseases characterised by fibrosis, by compounds that may be developed as effective adjunct therapies to current standard of care medication.

中文翻译：

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靶向NLRP3炎性小体以治疗心血管纤维化。

心血管纤维化是指由于对器官损伤或侮辱的异常伤口愈合反应而在受伤的心脏和血管中形成的疤痕组织。建立的纤维化成为慢性疾病进展的标志，并且是导致组织僵硬和功能障碍的关键因素，最终导致心力衰竭。由于伤口愈合和对心肌损伤的纤维化反应是多因素过程，因此仅针对疾病发病机理的特定促成因子的当前疗法提供了有限的总体抗纤维化功效。这样，最近的注意力已经转向针对人体的免疫系统，该系统可协调伤口对组织损伤的愈合反应。这篇评论的重点是已经发现NLRP3炎性小体的工作越来越多，一种多蛋白寡聚物复合物，通过产生IL-1β和IL-18负责激活炎症反应，是免疫系统启动的心血管修复促进剂，也是其持续激活后组织瘢痕形成的重要原因。综述总结了引发炎症小体复合物引发和激活的因素，活化的炎症小体复合物如何促进心血管病理生理和纤维化进程，以及利用遗传删除或药理学抑制作用的各种细胞培养和动物模型研究涉及的分子机制。炎性体的特定成分。最后，