title: Myostatin - From the Mighty Mouse to cardiovascular disease and cachexia.
abstract: In 1997, McPherron et al. created the so-called Mighty Mouse: owing to the knock-out of a new member of the TGF-β superfamily of peptides, this mouse line was extremely hypermuscular and also characterized by very low body fat. The new peptide, a powerful negative muscle regulator, was named myostatin. Apart from regulating skeletal muscle growth, myostatin has recently been reported to be significantly involved in different cardio-vascular and metabolic pathologies. This review is focused on these non-muscular myostatin actions. First, myostatin is intricately involved in regulating metabolism: it causes insulin resistance, and the advantageous metabolic profile achieved by myostatin inhibition is mainly attributable to its effects on skeletal muscle. Myostatin is further expressed in myocardium where it exerts anti-hypertrophic, but pro-fibrotic effects. Circulating and local myostatin is elevated in chronic heart failure and poses a major player in cardiac cachexia. Eventually, the current body of evidence regarding myostatin's significant involvement in different entities of the cachexia syndrome is summarized. Activin type-2 receptor antagonism and/or inhibitory myostatin antibodies have emerged as a promising therapeutic approach to treat the cachexia syndrome although the general applicability of this therapeutic approach to the human clinical situation has still to be demonstrated.
authors.affiliation: Immundiagnostik AG, Stubenwald-Allee 8a, 64625 Bensheim, Germany; Charité, University Medicine Berlin, Campus Mitte, Department of Cardiology and Angiology, Germany. Electronic address: thomas.dschietzig@t-online.de.
authors.forename: Thomas Bernd
authors.initials: TB
authors.lastname: Dschietzig
mesh_terms: D000818:Animals; D002100:Cachexia / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism
chemical_list: D055435:Myostatin
keywords: Cachexia; Heart failure; Insulin resistance; Metabolism; Myostatin