title: Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.
abstract: Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.
authors.affiliation: Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester Medical Center, Rochester, New York;
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Belmonte
authors.forename: Rashmi
authors.initials: R
authors.lastname: Ram
authors.forename: Deanne M
authors.initials: DM
authors.lastname: Mickelsen
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.forename: Burns C
authors.initials: BC
authors.lastname: Blaxall
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
chemical_list: D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D008840:Microfilament Proteins
keywords: cardiomyocyte; cardiomyopathy; heart; heart failure