TY - JOUR
T1 - When Stiffness Matters: Mechanosensing in Heart Development and Disease
AU - Gaetani, Roberto
AU - Zizzi, Eric Adriano
AU - Deriu, Marco Agostino
AU - Morbiducci, Umberto
AU - Pesce, Maurizio
AU - Messina, Elisa
N1 - Funding Information:
This research has been funded by the Horizon 2020 initiative program, grant agreement number 755523-MEDIRAD. The Virtuous project, funded by the European Union’s Horizon 2020 Research and Innovation Programme under the Maria Skłodowska-Curie—RISE Grant Agreement No. 872181.
Publisher Copyright:
© Copyright © 2020 Gaetani, Zizzi, Deriu, Morbiducci, Pesce and Messina.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/25
Y1 - 2020/5/25
N2 - During embryonic morphogenesis, the heart undergoes a complex series of cellular phenotypic maturations (e.g., transition of myocytes from proliferative to quiescent or maturation of the contractile apparatus), and this involves stiffening of the extracellular matrix (ECM) acting in concert with morphogenetic signals. The maladaptive remodeling of the myocardium, one of the processes involved in determination of heart failure, also involves mechanical cues, with a progressive stiffening of the tissue that produces cellular mechanical damage, inflammation, and ultimately myocardial fibrosis. The assessment of the biomechanical dependence of the molecular machinery (in myocardial and non-myocardial cells) is therefore essential to contextualize the maturation of the cardiac tissue at early stages and understand its pathologic evolution in aging. Because systems to perform multiscale modeling of cellular and tissue mechanics have been developed, it appears particularly novel to design integrated mechano-molecular models of heart development and disease to be tested in ex vivo reconstituted cells/tissue-mimicking conditions. In the present contribution, we will discuss the latest implication of mechanosensing in heart development and pathology, describe the most recent models of cell/tissue mechanics, and delineate novel strategies to target the consequences of heart failure with personalized approaches based on tissue engineering and induced pluripotent stem cell (iPSC) technologies.
AB - During embryonic morphogenesis, the heart undergoes a complex series of cellular phenotypic maturations (e.g., transition of myocytes from proliferative to quiescent or maturation of the contractile apparatus), and this involves stiffening of the extracellular matrix (ECM) acting in concert with morphogenetic signals. The maladaptive remodeling of the myocardium, one of the processes involved in determination of heart failure, also involves mechanical cues, with a progressive stiffening of the tissue that produces cellular mechanical damage, inflammation, and ultimately myocardial fibrosis. The assessment of the biomechanical dependence of the molecular machinery (in myocardial and non-myocardial cells) is therefore essential to contextualize the maturation of the cardiac tissue at early stages and understand its pathologic evolution in aging. Because systems to perform multiscale modeling of cellular and tissue mechanics have been developed, it appears particularly novel to design integrated mechano-molecular models of heart development and disease to be tested in ex vivo reconstituted cells/tissue-mimicking conditions. In the present contribution, we will discuss the latest implication of mechanosensing in heart development and pathology, describe the most recent models of cell/tissue mechanics, and delineate novel strategies to target the consequences of heart failure with personalized approaches based on tissue engineering and induced pluripotent stem cell (iPSC) technologies.
KW - cardiac regeneration
KW - cardiac tissue engineering
KW - mechanosensing and regulation
KW - stiffness
KW - tissue modeling
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U2 - 10.3389/fcell.2020.00334
DO - 10.3389/fcell.2020.00334
M3 - Review article
AN - SCOPUS:85086231330
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
SN - 2296-634X
M1 - 334
ER -