ORIGINAL CONTRIBUTION Cardiac remodeling is not modulated by overexpression of muscle LIM protein (MLP) Christian Kuhn • Derk Frank • Franziska Dierck • Ulrike Oehl • Jutta Krebs • Rainer Will • Lorenz H. Lehmann • Johannes Backs • Hugo A. Katus • Norbert Frey Received: 24 August 2010 / Revised: 14 February 2012 / Accepted: 7 March 2012 Ó Springer-Verlag 2012 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 hypoth- esized that overexpression of MLP might change the hyper- trophic 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 lit- termates. Moreover, neither contractile dysfunction nor path- ological 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 infu- sion 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. Keywords Calcineurin Á Cardiomyopathy Á CSRP3 Á Hypertrophy Á MLP Introduction Muscle LIM protein (MLP/CSRP3/CRP3) is a 194 amino acid protein that belongs to a family of cysteine rich proteins (CRPs). Like the other members of this family, CRP1 and CRP2, MLP is a LIM only protein that carries two LIM domains associated with glycine-rich repeats [26]. While MLP is highly expressed in striated muscle [1], CRP1 and CRP2 are enriched in organs containing large amounts of smooth muscle cells [21, 24]. Whereas MLP was initially described as a positive regulator of myogenic differentiation [1], its homozygous deletion in mice results in cardiac hypertrophy and severe dilated cardiomyopathy [2, 23]. Consistently, mutations in the csrp3 gene have been identi- fied in human patients that lead to either dilated or hyper- trophic cardiomyopathy [6, 15, 16, 22, 27, 31, 34]. Very recently, it could also be shown that MLP carrying a W4R mutation is sufficient to cause hypertrophic cardiomyopathy in both homozygous and heterozygous knock-in mice [28]. However, still little is known about the precise cellular function of MLP in cardiomyocytes and even its subcellular localization is still controversial [2, 4, 15, 27]. The LIM domain is thought to be a protein–protein-binding interface [26]. Several interacting proteins of MLP have been found, C. Kuhn and D. Frank contributed equally to the work. Electronic supplementary material The online version of this article (doi:10.1007/s00395-012-0262-8) contains supplementary material, which is available to authorized users. C. Kuhn Á D. Frank Á F. Dierck Á N. Frey (&) Department of Internal Medicine III, Cardiology and Angiology, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105 Kiel, Germany e-mail: norbert.frey@uk-sh.de U. Oehl Á J. Krebs Á R. Will Á L. H. Lehmann Á J. Backs Á H. A. Katus Department of Internal Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany 123 Basic Res Cardiol (2012) 107:262 DOI 10.1007/s00395-012-0262-8