title: Cardiac remodeling is not modulated by overexpression of muscle LIM protein (MLP).
abstract: Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. We thus hypothesized that overexpression of MLP might change the hypertrophic response to cardiac stress. In order to answer the question whether MLP modulates cardiac hypertrophy in vivo, we generated a novel transgenic mouse model with cardiac-specific overexpression of MLP. Three independent transgenic lines did not show a pathological phenotype under baseline conditions. Specifically, contractile function and heart weight to body weight ratios at different ages were normal. Next, the transgenic animals were challenged with pressure overload due to aortic constriction. Surprisingly, transgenic mice developed cardiac hypertrophy to the same extent as their wild-type littermates. Moreover, neither contractile dysfunction nor pathological gene expression in response to pressure overload were differentially affected by MLP overexpression. Finally, in a milder in vivo model of hypertrophy induced by chronic infusion of angiotensin-II, cardiac mass and hypertrophic gene expression were again identical in MLP transgenic mice and controls. Taken together, we provide evidence that cardiac overexpression of MLP does not modulate the heart's response to various forms of pathological stress.
authors.affiliation: Department of Internal Medicine III, Cardiology and Angiology, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kuhn
authors.forename: Derk
authors.initials: D
authors.lastname: Frank
authors.forename: Franziska
authors.initials: F
authors.lastname: Dierck
authors.forename: Ulrike
authors.initials: U
authors.lastname: Oehl
authors.forename: Jutta
authors.initials: J
authors.lastname: Krebs
authors.forename: Rainer
authors.initials: R
authors.lastname: Will
authors.forename: Lorenz H
authors.initials: LH
authors.lastname: Lehmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Backs
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000601:surgery; D001794:Blood Pressure; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005838:Genotype; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008026:Ligation; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D014463:Ultrasonography; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D060588:LIM Domain Proteins; D009124:Muscle Proteins; C090114:cysteine and glycine-rich protein 3; D000804:Angiotensin II