title: Thrombospondin-4, tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14: novel extracellular matrix modulating factors in cardiac remodelling.
abstract: Cardiac remodelling is defined as changes in the size, shape, and function of the heart, which are most commonly caused by hypertension-induced left ventricular hypertrophy and myocardial infarction. Both neurohumoral and inflammatory factors have critical roles in the regulation of cardiac remodelling. A characteristic feature of cardiac remodelling is modification of the extracellular matrix (ECM), often manifested by fibrosis, a process that has vital consequences for the structure and function of the myocardium. In addition to established modulators of the ECM, the matricellular protein thrombospondin-4 (TSP-4) as well as the tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 has been recently shown to modulate cardiac ECM. TSP-4 null mice develop pronounced cardiac hypertrophy and fibrosis with defects in collagen maturation in response to pressure overload. TWEAK and Fn14 belong to the tumour necrosis factor superfamily of proinflammatory cytokines. Recently it was shown that elevated levels of circulating TWEAK via Fn14 critically affect the cardiac ECM, characterized by increasing fibrosis and cardiomyocyte hypertrophy in mice. Here we review the literature concerning the role of matricellular proteins and inflammation in cardiac ECM remodelling, with a special focus on TSP-4, TWEAK, and its receptor Fn14.
authors.affiliation: Institute of Biomedicine, Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Erja
authors.initials: E
authors.lastname: Mustonen
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
mesh_terms: D000818:Animals; D000074049:Cytokine TWEAK; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D000074050:TWEAK Receptor; D019699:Thrombospondins / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D000074049:Cytokine TWEAK; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D019699:Thrombospondins; C000613299:Tnfrsf12a protein, mouse; D048069:Tumor Necrosis Factors; C101864:thrombospondin 4