TRAIL and Cardiovascular Disease—A Risk Factor or Risk Marker: A Systematic Review

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic protein showing broad biological functions. Data from animal studies indicate that TRAIL may possibly contribute to the pathophysiology of cardiomyopathy, atherosclerosis, ischemic stroke and abdominal aortic aneurysm. It has been also suggested that TRAIL might be useful in cardiovascular risk stratification. This systematic review aimed to evaluate whether TRAIL is a risk factor or risk marker in cardiovascular diseases (CVDs) focusing on major adverse cardiovascular events. Two databases (PubMed and Cochrane Library) were searched until December 2020 without a year limit in accordance to the PRISMA guidelines. A total of 63 eligible original studies were identified and included in our systematic review. Studies suggest an important role of TRAIL in disorders such as heart failure, myocardial infarction, atrial fibrillation, ischemic stroke, peripheral artery disease, and pulmonary and gestational hypertension. Most evidence associates reduced TRAIL levels and increased TRAIL-R2 concentration with all-cause mortality in patients with CVDs. It is, however, unclear whether low TRAIL levels should be considered as a risk factor rather than a risk marker of CVDs. Further studies are needed to better define the association of TRAIL with cardiovascular diseases.

Longitudinal Study Reveals Long-Term Proinflammatory Proteomic Signature After Ischemic Stroke Across Subtypes

“…26 Data from animal studies indicate that TRAIL may contribute to the pathophysiology of atherosclerosis and ischemic stroke. 27 Another TNF superfamily member, TRANCE (or TNFSF11), was most elevated in SAO stroke in the acute phase. Circulating TRANCE has been linked to vascular calcification and arterial damage 28 and elevated serum levels of TRANCE have been associated with incident cardiovascular disease (defined as ischemic stroke, transient ischemic attack, myocardial infarction, or vascular death).…”

Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

“…TRAIL‐R2 is a cell surface death receptor that is expressed on endothelium, vascular smooth muscle cells (VSMCs) and macrophages, is highly expressed in the heart, and can also be released in a soluble form (sTRAIL) 65–67 . It predicts all‐cause mortality after MI 68 and HF development 67 .…”

“…64 TRAIL-R2 is a cell surface death receptor that is expressed on endothelium, vascular smooth muscle cells (VSMCs) and macrophages, is highly expressed in the heart, and can also be released in a soluble form (sTRAIL). [65][66][67] It predicts all-cause mortality after MI 68 and HF development. 67 In most cells TRAIL-R2 stimulates apoptosis, whereas in cardiomyocytes it promotes hypertrophy while inhibiting fibrosis after injury.…”

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

“…In some circumstances it may protect, while in others it may contribute to pathogenesis. Furthermore, it is unclear as to whether TRAIL is a risk factor or a risk marker in CVDs [ 18 ]. This review summarises our current understanding of TRAIL signals in atherosclerotic vascular disease as well as conditions of the heart.…”