Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK)/Fibroblast Growth Factor-Inducible 14 (Fn14) Axis in Cardiovascular Diseases: Progress and Challenges

Abstract

Cardiovascular diseases (CVD) are the leading cause of mortality in Western countries. CVD include several pathologies, such as coronary artery disease, stroke, peripheral artery disease, and aortic aneurysm, among others. All of them are characterized by a pathological vascular remodeling in which inflammation plays a key role. Interaction between different members of the tumor necrosis factor superfamily and their cognate receptors induce several biological actions that may participate in CVD. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), are abundantly expressed during pathological cardiovascular remodeling. The TWEAK/Fn14 axis controls a variety of cellular functions, such as proliferation, differentiation, and apoptosis, and has several biological functions, such as inflammation and fibrosis that are linked to CVD. It has been demonstrated that persistent TWEAK/Fn14 activation is involved in both vessel and heart remodeling associated with acute and chronic CVD. In this review, we summarized the role of the TWEAK/Fn14 axis during pathological cardiovascular remodeling, highlighting the cellular components and the signaling pathways that are involved in these processes.

Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation

“…Our work also identified potential upstream regulators of systemic inflammation and fibrosis, such as TNFα, IFNγ, and TGFβ1. EGF, another identified upstream regulator, is also known to promote angiogenesis through induction of autocrine VEGF expression [ 18 ], to regulate inflammation, through its effects on TNSRSF12A (also known as FN14) [ 19 ] and to regulate matrix turnover through effects on MMP12, which itself regulates angiogenesis and inflammation [ 20 ]. The cellular oncogene c-fos, also found in our screen for upstream regulators, promotes angiogenesis through the induction of VEGF [ 21 ].…”

Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients Before and After Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation

“…Our work has also identified potential upstream regulators of systemic inflammation and fibrosis, such as TNF, IFN and TGF1. EGF, another identified upstream regulator, is also known to promote angiogenesis through induction of autocrine VEGF expression [18], to regulate inflammation through its effects on TNSRSF12A (also known as FN14) [19] and to regulate matrix turnover through effects on MMP12, which itself regulates angiogenesis and inflammation [20]. The cellular oncogene c-fos, also found in our screen for upstream regulators, promotes angiogenesis through the induction of VEGF [21].…”

sTWEAK as Predictor of Stroke Recurrence in Ischemic Stroke Patients Treated With Reperfusion Therapies

“…Furthermore, after the first stroke, Wallerian degeneration (WD) could develop and cause new white matter hyperintensities related with LA progression ( 51 ). Four, serum levels of sTWEAK do not represent a specific marker of a particular process; patients with multiple sclerosis, heart failure, or atherosclerosis show also variations in the sTWEAK levels ( 52 ). However, we investigate the possible relationship among sTWEAK—LA—stroke recurrence in reperfused IS patients.…”