Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Academic Editor: Corina Lorz
Increasing experimental evidence suggests that both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its soluble decoy receptor osteoprotegerin (OPG) are involved in vascular biology. In particular, emerging data indicate that recombinant soluble TRAIL may act as a molecule with potential anti-inflammatory activity in vascular physiopathology. Conversely, the presence of leukocytes expressing membrane-bound TRAIL in atherosclerotic lesions might be involved in the destabilization of atherosclerotic plaques by inducing apoptotic cell death of vascular smooth muscle cells in an inflammatory milieu. Also OPG seems to be involved in vascular homeostasis, by acting in a paracrine or autocrine manner as a survival factor for endothelial cells. However, an increased production of OPG may have a role in the development of vascular dysfunction likely by multiple potential mechanisms, not only related to its ability to neutralize TRAIL-activity but also mediated by its heparin-binding domain. In this review we have summarized and discussed both in vitro and in vivo data that suggest potential roles of TRAIL and OPG in vascular physiopathology. Further studies are needed to address how the TRAIL/OPG interaction, their reciprocal balance and/or interplay affect vascular biology in order to design innovative therapeutic strategies in vascular diseases.