人食管癌相关基因 4 (ECRG-4) 编码一个 148 个氨基酸的前原肽，可以组织依赖性地加工成多个小肽，这些小肽具有与食管癌肿瘤抑制功能不同、相似或相反的多种功能。全长 Ecrg4。 Ecrg-4 通过其信号肽共价结合到细胞表面，与先天免疫复合物 (TLR4-CD14-MD2) 共定位，并在维持上皮和白细胞稳态中充当“哨兵”分子，这意味着 Ecrg-4 的存在细胞表面 Ecrg-4 的存在标志着维持稳态，而由于组织损伤而导致的 Ecrg-4 损失会激活促炎和组织增殖反应，并且 Ecrg-4 的水平在伤口时逐渐恢复到损伤前的水平康复。有趣的是，Ecrg-4也在心脏及其传导系统、内皮细胞和血管平滑肌细胞中高表达。越来越多的证据表明，Ecrg-4 参与心率/节律控制、心房颤动的发生、阿霉素诱导的心脏毒性、心脏缺血反应和颈动脉体缺氧反应、动脉粥样硬化的发病机制，以及可能的特发性扩张型心肌病的地方性发病率。这些初步发现表明，Ecrg-4 也可能在心血管系统中充当“哨兵”分子。在此，我们简单回顾一下ECRG-4作为抑癌基因的基本特征及其对炎症和细胞凋亡的调节功能；总结了有关其在心血管系统中的分布和参与 CVD 发展的发现，并讨论了其作为维持心血管系统稳态的新型治疗靶点的潜力。版权所有 © 2023。由 Elsevier B.V. 出版。

Human esophageal cancer related gene-4 (ECRG-4) encodes a 148-aminoacid pre-pro-peptide that can be processed tissue-dependently into multiple small peptides possessing multiple functions distinct from, similar to, or opposite to the tumor suppressor function of the full-length Ecrg4. Ecrg-4 is covalently bound to the cell surface through its signal peptide, colocalized with the innate immunity complex (TLR4-CD14-MD2), and functions as a 'sentinel' molecule in the maintenance of epithelium and leukocyte homeostasis, meaning that the presence of Ecrg-4 on the cell surface signals the maintained homeostasis, whereas the loss of Ecrg-4 due to tissue injury activates pro-inflammatory and tissue proliferative responses, and the level of Ecrg-4 gradually returns to its pre-injury level upon wound healing. Interestingly, Ecrg-4 is also highly expressed in the heart and its conduction system, endothelial cells, and vascular smooth muscle cells. Accumulating evidence has shown that Ecrg-4 is involved in cardiac rate/rhythm control, the development of atrial fibrillation, doxorubicin-induced cardiotoxicity, the ischemic response of the heart and hypoxic response in the carotid body, the pathogenesis of atherosclerosis, and likely the endemic incidence of idiopathic dilated cardiomyopathy. These preliminary discoveries suggest that Ecrg-4 may function as a 'sentinel' molecule in cardiovascular system as well. Here, we briefly review the basic characteristics of ECRG-4 as a tumor suppressor gene and its regulatory functions on inflammation and apoptosis; summarize the discoveries about its distribution in cardiovascular system and involvement in the development of CVDs, and discuss its potential as a novel therapeutic target for the maintenance of cardiovascular system homeostasis.Copyright © 2023. Published by Elsevier B.V.