TRAIL inhibition by soluble death receptor 5 protects against acute myocardial infarction in rats

Wang, Mingli; Wei, Yinxiang; Wang, Xuance; Ma, Fanni; Zhu, Wenwen; Chen, Xi; Zhong, Xiaoming; Li, Shulian; Zhang, Jun; Liu, Guangchao; Wang, Yaohui; Ma, Yuanfang

doi:10.1007/s00380-022-02197-7

Cited by 2 publications

(4 citation statements)

References 46 publications

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“…TRAIL and its receptors are expressed in normal and diseased human and rodent hearts at varying levels [ 51 , 74 , 102 , 103 ], although the impact of TRAIL signals in the heart is not fully elucidated. Apoptosis and proliferation play key roles under normal and pathogenic conditions, but it is not clear if TRAIL play a protective or detrimental role here.…”

Section: Trail Signalling In the Myocardiummentioning

confidence: 99%

“…Blocking DR5 using a soluble immunoglobulin fusion protein (sDR5-fc) in a heart failure model that prevents cardiac cell death and inflammation, preserves ejection fraction and fractional shortening, reduces fibrosis, and prevents ventricular wall thinning, findings observed in rodents, pigs, and monkeys [ 79 ]. Silencing DR5 in an MI model in rats also reduced myocardial damage and infarct size, and it reduced the cardiac expression of apoptotic mediators [ 74 ]. These imply that under certain conditions, the activation of TRAIL signals in the heart could be detrimental, and a blockade of TRAIL signalling may be used as a potential therapeutic.…”

Section: Trail Signalling In the Myocardiummentioning

confidence: 99%

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The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases

Kelland

Patil

Patel

et al. 2023

IJMS

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TNF-related apoptosis-inducing ligand (TRAIL) was originally discovered, almost 20 years ago, for its ability to kill cancer cells. More recent evidence has described pleiotropic functions, particularly in the cardiovascular system. There is potential for TRAIL concentrations in the circulation to act as prognostic and/or diagnostic factors for cardiovascular diseases (CVD). Pre-clinical studies also describe the therapeutic capacity for TRAIL signals, particularly in the context of atherosclerotic disease and diseases of the myocardium. Because diabetes mellitus significantly contributes to the progression and pathogenesis of CVDs, in this review we highlight recent evidence for the prognostic, diagnostic, and therapeutic potential of TRAIL signals in CVDs, and where relevant, the impact of diabetes mellitus. A greater understanding of how TRAIL signals regulate cardiovascular protection and pathology may offer new diagnostic and therapeutic avenues for patients suffering from CVDs.

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Section: Trail Signalling In the Myocardiummentioning

confidence: 99%

Section: Trail Signalling In the Myocardiummentioning

confidence: 99%

The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases

Kelland

Patil

Patel

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…Human data is confounding with some studies suggesting a protective and other pointed towards a detrimental role for TRAIL signaling in the heart. However, administration of soluble DR5 in rats with AMI to prevent TRAIL from binding to functional DRs resulted in reduced infarct size and improved markers of cardiac damage such as serum cardiac troponin I and creatine kinase-MB (CK-MB) ( Wang et al, 2023 ). In a separate study, blocking TRAIL with a soluble DR5 immunoglobulin fusion protein prevented cardiac cell death and inflammation in rats, pigs and monkeys ( Wang et al, 2020 ).…”

Section: Clinical Studiesmentioning

confidence: 99%

“…Should inhibiting TRAIL/DR5 signaling prove useful in the heart, therapeutic options are more limited. In preclinical rodent models, administration of soluble DR5, which sequesters TRAIL to prevent its binding, has been effective ( Wang et al, 2023 ). In large animal studies, sequestering TRAIL using a soluble DR5 immunoglobulin fusion protein has been used to antagonize DR5 ( Wang et al, 2020 ).…”

Section: Clinical Studiesmentioning

confidence: 99%

TRAIL and its receptors in cardiac diseases

Grisanti

2023

Front. Physiol.

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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.

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TRAIL inhibition by soluble death receptor 5 protects against acute myocardial infarction in rats

Cited by 2 publications

References 46 publications

The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases

The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases

TRAIL and its receptors in cardiac diseases

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