Immune dysregulation has been identified as a critical cause of the most common types of cardiovascular diseases (CVDs). Notably, the innate and adaptive immune responses under physiological conditions are typically regulated with high sensitivity to avoid the exacerbation of inflammation, but any dysregulation can probably be associated with CVDs. In this respect, progranulin (PGRN) serves as one of the main components of the regulation of inflammatory processes, which significantly contributes to the immunopathogenesis of such disorders. PGRN has been introduced among the secreted growth factors as one related to wound healing, inflammation, and human embryonic development, as well as a wide variety of autoimmune diseases. The relationship between the serum PGRN and TNF-α ratio with the spontaneous bacterial peritonitis constitute one of the independent predictors of these conditions. The full-length PGRN can thus effectively reduce the calcification of valve interstitial cells, and the granulin precursor (GRN), among the degradation products of PGRN, can be beneficial. Moreover, it was observed that, PGRN protects the heart against ischemia-reperfusion injury. Above all, PGRN also provides protection in the initial phase following myocardial ischemia-reperfusion injury. The protective impact of PGRN on this may be associated with the early activation of the PI3K/Akt signaling pathway. PGRN also acts as a protective factor in hyperhomocysteinemia, probably by down-regulating the wingless-related integration site Wnt/β-catenin signaling pathway. Many studies have further demonstrated that SARS-CoV-2 (COVID-19) has dramatically increased the risks of CVDs due to inflammation, so PGRN has drawn much more attention among scholars. Lysosomes play a pivotal role in the inflammation process, and PGRN is one of the key regulators in their functioning, which contributes to the immunomodulatory mechanism in the pathogenesis of CVDs. Therefore, investigation of PGRN actions can help find new prospects in the treatment of CVDs. This review aims to summarize the role of PGRN in the immunopathogenesis of CVD, with an emphasis on its treatment.

中文翻译：

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颗粒蛋白前体 (PGRN) 作为炎症调节剂和心血管疾病免疫发病机制的关键因素

免疫失调已被确定为最常见类型的心血管疾病 (CVD) 的关键原因。值得注意的是，生理条件下的先天性和适应性免疫反应通常受到高度敏感的调节，以避免炎症恶化，但任何失调都可能与 CVD 相关。在这方面，颗粒体蛋白前体 (PGRN) 作为调节炎症过程的主要成分之一，显着促进了此类疾病的免疫发病机制。PGRN 已被引入分泌性生长因子中，作为一种与伤口愈合、炎症和人类胚胎发育以及多种自身免疫性疾病相关的因子。血清 PGRN 和 TNF-α 比值与自发性细菌性腹膜炎之间的关系构成了这些病症的独立预测因子之一。因此，全长 PGRN 可以有效减少瓣膜间质细胞的钙化，而 PGRN 降解产物中的颗粒蛋白前体 (GRN) 可能是有益的。此外，据观察，PGRN 保护心脏免受缺血再灌注损伤。最重要的是，PGRN 还在心肌缺血再灌注损伤后的初始阶段提供保护。PGRN 对此的保护作用可能与 PI3K/Akt 信号通路的早期激活有关。PGRN 还作为高同型半胱氨酸血症的保护因子，可能是通过下调与无翅相关的整合位点 Wnt/β-catenin 信号通路。许多研究进一步表明，SARS-CoV-2（COVID-19）由于炎症显着增加了心血管疾病的风险，因此PGRN受到了更多学者的关注。溶酶体在炎症过程中起着关键作用，PGRN 是其功能的关键调节因子之一，有助于 CVD 发病机制中的免疫调节机制。因此，对PGRN作用的研究有助于发现CVD治疗的新前景。本综述旨在总结 PGRN 在 CVD 免疫发病机制中的作用，并重点介绍其治疗。PGRN 是其功能的关键调节因子之一，有助于 CVD 发病机制中的免疫调节机制。因此，对PGRN作用的研究有助于发现CVD治疗的新前景。本综述旨在总结 PGRN 在 CVD 免疫发病机制中的作用，并重点介绍其治疗。PGRN 是其功能的关键调节因子之一，有助于 CVD 发病机制中的免疫调节机制。因此，对PGRN作用的研究有助于发现CVD治疗的新前景。本综述旨在总结 PGRN 在 CVD 免疫发病机制中的作用，并重点介绍其治疗。