FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction
Open Access
- 24 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Basic Research in Cardiology
- Vol. 115 (2), 1-15
- https://doi.org/10.1007/s00395-019-0767-5
Abstract
Aims The cytoskeletal signaling protein four and-a-half LIM domains 1 (FHL-1) has recently been identified as a novel key player in pulmonary hypertension as well as in left heart diseases. In this regard, FHL-1 has been implicated in dysregulated hypertrophic signaling in pulmonary arterial smooth muscle cells leading to pulmonary hypertension. In mice, FHL-1-deficiency (FHL-1(-/-)) led to an attenuated hypertrophic signaling associated with a blunted hypertrophic response of the pressure-overloaded left ventricle (LV). However, the role of FHL-1 in right heart hypertrophy has not yet been addressed. Methods and results We investigated FHL-1 expression in C57Bl/6 mice subjected to chronic biomechanical stress and found it to be enhanced in the right ventricle (RV). Next, we subjected FHL-1(-/-) and corresponding wild-type mice to pressure overload of the RV by pulmonary arterial banding for various time points. However, in contrast to the previously published study in LV-pressure overload, which was confirmed here, RV hypertrophy and hypertrophic signaling was not diminished in FHL-1(-/-) mice. In detail, right ventricular pressure overload led to hypertrophy, dilatation and fibrosis of the RV from both FHL-1(-/-) and wild-type mice. RV remodeling was associated with impaired RV function as evidenced by reduced tricuspid annular plane systolic excursion. Additionally, PAB induced upregulation of natriuretic peptides and slight downregulation of phospholamban and ryanodine receptor 2 in the RV. However, there was no difference between genotypes in the degree of expression change. Conclusion FHL-1 pathway is not involved in the control of adverse remodeling in the pressure overloaded RV.This publication has 49 references indexed in Scilit:
- Right-To-Left Ventricular Differences in the Expression of Mitochondrial Hexokinase and Phosphorylation of AktCellular Physiology and Biochemistry, 2013
- Molecular Signature of a Right Heart Failure Program in Chronic Severe Pulmonary HypertensionAmerican Journal of Respiratory Cell and Molecular Biology, 2011
- Homogenous protein programming in the mammalian left and right ventricle free wallsPhysiological Genomics, 2011
- The histone trimethyllysine demethylase JMJD2A promotes cardiac hypertrophy in response to hypertrophic stimuli in miceJCI Insight, 2011
- Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strainsPhysiological Genomics, 2010
- Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in miceJCI Insight, 2009
- An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in miceJCI Insight, 2008
- Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosisAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Four and a Half LIM Protein 1 Binds Myosin-binding Protein C and Regulates Myosin Filament Formation and Sarcomere AssemblyOnline Journal of Public Health Informatics, 2006
- Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcementThe Journal of cell biology, 2005