Journalartikel

Jahr der Veröffentlichung: 2020

Zeitschrift: Basic Research in Cardiology

Bandnummer: 115

Heftnummer: 2

ISSN: 0300-8428

eISSN: 1435-1803

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1007/s00395-019-0767-5

Verlag: Springer

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.

Harvard-Zitierstil: Veith, C., Neghabian, D., Luitel, H., Wilhelm, J., Egemnazarov, B., Muntanjohl, C., et al. (2020) FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction, Basic Research in Cardiology, 115(2), Article 17. https://doi.org/10.1007/s00395-019-0767-5

APA-Zitierstil: Veith, C., Neghabian, D., Luitel, H., Wilhelm, J., Egemnazarov, B., Muntanjohl, C., Fischer, J., Dahal, B., Schermuly, R., Ghofrani, H., Grimminger, F., Fink, L., Kwapiszewska, G., Weissmann, N., & Sydykov, A. (2020). FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction. Basic Research in Cardiology. 115(2), Article 17. https://doi.org/10.1007/s00395-019-0767-5