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The role of mechanotransduction in heart failure pathobiology—a concise review

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Abstract

This review evaluates the role of mechanotransduction (MT) in heart failure (HF) pathobiology. Cardiac functional and structural modifications are regulated by biomechanical forces. Exposing cardiomyocytes and the myocardial tissue to altered biomechanical stress precipitates changes in the end-diastolic wall stress (EDWS). Thereby various interconnected biomolecular pathways, essentially mediated and orchestrated by MT, are launched and jointly contribute to adapt and remodel the myocardium. This cardiac MT-mediated feedback decisively determines the primary cardiac cellular and tissue response, the sort (concentric or eccentric) of hypertrophy/remodeling, to mechanical and/or hemodynamic alterations. Moreover, the altered EDWS affects the diastolic myocardial properties independent of the systolic function, and elevated EDWS causes diastolic dysfunction. The close interconnection between MT pathways and the cell nucleus, the genetic endowment, principally allows for the wide variety of phenotypic appearances. However, demographic, environmental features, comorbidities, and also the genetic make-up may modulate the phenotypic result. Cardiac MT takes a fundamental and superordinate position in the myocardial adaptation and remodeling processes in all HF categories and phenotypes. Therefore, the effects of MT should be integrated in all our scientific, clinical, and therapeutic considerations.

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Notes

  1. Fibrotic tissue replaces specific myocardial tissue (replacement fibrosis) if myocardial tissue is lost (notably if necrotic) such as in case of myocardial infarction, myocarditis, etc. [Herum K (2017) J Clin Invest 6, 53; doi:https://doi.org/10.3390/jcm6050053]. Reactive myocardial fibrosis occurs as an accompanying process in case of hypertrophic (eccentric and concentric) remodeling [Weber KT (2013) Nat Rev. Cardiol 10: 15–26; Herum K (2017) J Clin Invest 6, 53; doi:https://doi.org/10.3390/jcm6050053]. However, there is a very strong interconnection and coupling between any inflammatory activity and pro-fibrotic pathways in response to any threat the organism is exposed to [Chen L (2018) Oncotarget 9: 7204–7218; Chen L (2017) Nat Immunol 18: 825].

  2. The term remodeling describes all cardiac molecular, cellular, tissue, and geometrical changes displayed in response to any bio-physical stress the heart is exposed to, which collectively form and determine the modified, adapted heart structure and function [Omens JJ (2007). In: Cardiac mechanotransduction by Tavi and Weckstroem. New York: Springer Science and Business Media, chapter 5, pp. 78–92; Cohn JN (2000) J Am Coll Cardiol 35: 596–582].

  3. Myocardial stiffness, basically referring to “material properties” of the cardiac tissue (namely the cardiomyocytes and of the extracellular matrix) [Chaturvedi RR et al. (2010) Circulation 121: 979–988], and chamber stiffness need to be thoroughly distinguished [Gaasch WH et al. (1982) Eur Heart J 3 (Suppl A): A 139 – A 145].

  4. Natriuretic peptides take adaptive measures by promoting natriuresis and diuresis, inhibiting the sympathetic nervous system and renin-angiotensin-aldosterone activity, and display an arterial vasodilatory effect [Adams jr KF (2003) Am Heart J 145: S 34–S 46]. As such, natriuretic peptides counteract the neurohumoral systems.

  5. BNP is a load-indiced cardiomyocyte specific marker of modified gene expression [Meluzin J, Tomandl, J (2015) Hindawi Volume 2015, Article ID 426045, 9 pages].

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Authors and Affiliations

  1. Institute of Evolutionary Medicine, University of Zurich, Zurich, Switzerland

    Wolfgang Krueger, Nicole Bender, Martin Haeusler & Maciej Henneberg

  2. Medical University Department, Kantonsspital Aarau, Aarau, Switzerland

    Wolfgang Krueger

  3. Adelaide Medical School, The University of Adelaide, Adelaide, Australia

    Maciej Henneberg

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Krueger, W., Bender, N., Haeusler, M. et al. The role of mechanotransduction in heart failure pathobiology—a concise review. Heart Fail Rev 26, 981–995 (2021). https://doi.org/10.1007/s10741-020-09915-1

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