心血管疾病是全球主要的死因之一。心脏受到缺血性损伤和压力过载等多种伤害时，心肌细胞的丧失会降低心脏功能，因其再生能力有限，同时促进心脏重塑，从而进一步损害心脏。心肌细胞死亡主要通过坏死和凋亡两种机制发生。凋亡是一种高度调控的细胞死亡形式，可以通过内在（线粒体）或外在（受体介导）通路发生。外在凋亡是通过一类肿瘤坏死因子受体(Tumor Necrosis Receptor, TNF)家族受体——“死亡受体”发生的。虽然一些与死亡受体配体有关的配体已在心脏中大量研究，如TNF-α，但其他配体则几乎没有研究。其中一个对心脏TNF相关配体缺乏研究的是TNF相关凋亡诱导配体(TNF-Related Apoptosis Inducing Ligand, TRAIL)。TRAIL与两种凋亡诱导受体，即死亡受体(DR)4和DR5结合。此外，还存在三种TRAIL假死灵受体，分别为假死灵受体(DcR)1、DcR2和骨保护素(OPG)。尽管TRAIL在肿瘤领域已广泛研究，因其能选择性诱导转化细胞类型的凋亡，但新兴的临床证据指向了TRAIL及其受体在心脏病理中的作用。本文将重点介绍TRAIL及其受体在心脏正常和病理状态下的现有认识。Copyright © 2023 Grisanti.

Cardiovascular disease is a leading cause of death worldwide. Loss of cardiomyocytes that occurs during many types of damage to the heart such as ischemic injury and stress caused by pressure overload, diminishes cardiac function due to their limited regenerative capacity and promotes remodeling, which further damages the heart. Cardiomyocyte death occurs through two primary mechanisms, necrosis and apoptosis. Apoptosis is a highly regulated form of cell death that can occur through intrinsic (mitochondrial) or extrinsic (receptor mediated) pathways. Extrinsic apoptosis occurs through a subset of Tumor Necrosis Receptor (TNF) family receptors termed "Death Receptors." While some ligands for death receptors have been extensively studied in the heart, such as TNF-α, others have been virtually unstudied. One poorly characterized cardiac TNF related ligand is TNF-Related Apoptosis Inducing Ligand (TRAIL). TRAIL binds to two apoptosis-inducing receptors, Death Receptor (DR) 4 and DR5. There are also three decoy TRAIL receptors, Decoy Receptor (DcR) 1, DcR2 and osteoprotegerin (OPG). While TRAIL has been extensively studied in the cancer field due to its ability to selectively induce apoptosis in transformed cell types, emerging clinical evidence points towards a role for TRAIL and its receptors in cardiac pathology. This article will highlight our current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.Copyright © 2023 Grisanti.