Mechanical regulation of cardiac development

Abstract

Mechanical forces are essential contributors to and unavoidable components of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development.

Bioengineering methods for myocardial regeneration

“…Cardiomyocytes mature under appropriate mechanical loading, whereas excessive loading can cause pathological hypertrophy and apoptosis [22]. The main types of mechanical loading are the wall shear stress caused by blood flow, and the strain caused by blood pressure and cell contractions (Figure 2A) [23]. Blood flow is present already at the early stages of embryogenesis, initially without a clear role in nourishment and oxygen supply, as evidenced by the lack of hemoglobin-mediated transport of oxygen in chick embryos until Hamburger-Hamilton stage 20 (HH20) [24, 25].…”

“…Blood flow is present already at the early stages of embryogenesis, initially without a clear role in nourishment and oxygen supply, as evidenced by the lack of hemoglobin-mediated transport of oxygen in chick embryos until Hamburger-Hamilton stage 20 (HH20) [24, 25]. Instead, diffusion is the main mechanism of nutrient and oxygen supply at the early stages of heart development [23, 26]. …”

“…Electrical signals are found both in the developing and the adult heart. Endogenous electrical fields in the developing vertebrate embryo have been widely documented [7], with spontaneous action potentials detected in the chick heart primordium as early as at stage HH9, and before detecting myocyte contractions [23, 28]. It is thought that direct current signals mediate cell migration during primitive streak formation and play roles in establishing the left-right asymmetry.…”

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

“…A second mechanism, myofibrillogenesis, ensures that sarcomeres serially register along acting bundles, creating the parallel arrays of myofibrils responsible for the cardiomyocyte striated appearance [3]. Through dedicated cell-cell junctions, myofibrils register across multiple cardiomyocytes creating myocardial sheets that wrap themselves around the cardiac chambers ensuring efficient pumping of blood in the circulation [4, 5]. …”

Measuring the micromechanical properties of embryonic tissues

“…It is well-known that culturing muscle strips requires applying a periodic longitudinal stress to the organ [23]. We are only starting to unveil the importance of mechanical stresses in the formation of other structures such as the lung [24], the heart [25] etc. Furthermore, the determination of the inotropic (contractile) effects on tissues (e.g.…”