title: The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence.
abstract: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that belongs to the tumour necrosis factor (TNF) cytokine superfamily. TRAIL is expressed by numerous cell types including vascular cells, immune cells and adipocytes. Although originally thought to induce apoptosis in malignant or transformed cells only, it is now known that TRAIL can bind up to 5 distinct receptors to activate complex signalling pathways, and is capable of exerting pleiotropic effects in non-transformed cells. In this respect, a number of clinical and animal studies point to the potential vasoprotective influence of TRAIL, with TRAIL deficiency being linked to accelerated atherosclerosis and vascular calcification. Moreover, exogenous TRAIL administration has been shown to exhibit anti-atherosclerotic activity in-vivo. In-vitro studies on TRAIL in this context have yielded conflicting results however, with evidence of both pro-atherogenic and vasoprotective effects ascribed to TRAIL. Notwithstanding these various studies, mechanistic information on the precise nature of TRAIL-mediated injury/protection within the vasculature, as well as the identity of the downstream molecular/cellular targets of TRAIL, is still quite limited. In this review, we will summarize our current knowledge of TRAIL regulation, signalling mechanisms, and its apparent involvement in CVD pathogenesis as a prelude to examining the existing evidence for TRAIL-mediated vasoprotection. To this end, extensive in vitro, in vivo, and clinical studies will be reviewed and critical findings highlighted.
authors.affiliation: Department of Academic Endocrinology and Diabetes, Royal College of Surgeons Medical School and Beaumont Hospital, Dublin 9, Ireland; School of Biotechnology, Dublin City University, Dublin 9, Ireland. Electronic address: hannahforde@gmail.com.
authors.forename: Hannah
authors.initials: H
authors.lastname: Forde
authors.affiliation: School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Emma
authors.initials: E
authors.lastname: Harper
authors.affiliation: Department of Academic Endocrinology and Diabetes, Royal College of Surgeons Medical School and Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Davenport
authors.affiliation: Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Rochfort
authors.affiliation: School of Health and Human Performance, Dublin City University, Dublin 9, Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Wallace
authors.affiliation: School of Health and Human Performance, Dublin City University, Dublin 9, Ireland.
authors.forename: Ronan P
authors.initials: RP
authors.lastname: Murphy
authors.affiliation: Department of Academic Endocrinology and Diabetes, Royal College of Surgeons Medical School and Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Diarmuid
authors.initials: D
authors.lastname: Smith
authors.affiliation: School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Cummins
mesh_terms: D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D006801:Humans; D065840:Protective Factors; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
keywords: Atherosclerosis; Cardiovascular disease; TRAIL; Vasoprotection