Influence of blood flow on cardiac development

Abstract

The role of hemodynamics in cardiovascular development is not well understood. Indeed, it would be remarkable if it were, given the dauntingly complex array of intricately synchronized genetic, molecular, mechanical, and environmental factors at play. However, with congenital heart defects affecting around 1 in 100 human births, and numerous studies pointing to hemodynamics as a factor in cardiovascular morphogenesis, this is not an area in which we can afford to remain in the dark. This review seeks to present the case for the importance of research into the biomechanics of the developing cardiovascular system. This is accomplished by i) illustrating the basics of some of the highly complex processes involved in heart development, and discussing the known influence of hemodynamics on those processes; ii) demonstrating how altered hemodynamic environments have the potential to bring about morphological anomalies, citing studies in multiple animal models with a variety of perturbation methods; iii) providing examples of widely used technological innovations which allow for accurate measurement of hemodynamic parameters in embryos; iv) detailing the results of studies in avian embryos which point to exciting correlations between various hemodynamic manipulations in early development and phenotypic defect incidence in mature hearts; and finally, v) stressing the relevance of uncovering specific biomechanical pathways involved in cardiovascular formation and remodeling under adverse conditions, to the potential treatment of human patients. The time is ripe to unravel the contributions of hemodynamics to cardiac development, and to recognize their frequently neglected role in the occurrence of heart malformation phenotypes.

Characterisation of the developing heart in a pressure overloaded model utilising RNA sequencing to direct functional analysis

“…Heart dilation has been seen in humans subsequent to a previous diagnosis of a hypertrophic heart, suggesting the heart is failing (Hamada et al ). Conversely, the developing or postnatal heart with a complex congenital defect (having two or more heart defects) is prone to abnormal haemodynamics, with a dilated heart seen as a secondary effect in some cases (Sanchez‐Gomez et al ; Courchaine et al ). In addition, a recent study has indicated that as heart development progresses (HH22 to HH36), the proximal part of the OFT (conus) becomes part of the right myocardial wall (Lazzarini et al ); this process could rescue the right ventricular wall from a dilating phenotype.…”

Understanding the Mechanobiology of Early Mammalian Development through Bioengineered Models

“…Crucially, the most recent models identify shear stresses at the node surface as drivers of local exocytic release of morphogens, thus directly implicating fluid mechanics (Solowiej-Wedderburn et al, 2019). Clear effects of shear stresses have additionally been described later in development, especially in the maturation and differentiation of vascular cell types (Courchaine et al, 2018;Hwa et al, 2017). When not flowing, embryonic fluids exert pressures, and these, too, have been implicated in multiple steps of early development (Navis and Bagnat, 2015).…”

Functional Morphology of the Cardiac Jelly in the Tubular Heart of Vertebrate Embryos

“…Comments on the significance of the CJ for the mechanical pump action of the early embryonic heart tube are also missed in contemporary monographs and textbooks on cardiac development [32,33]. Proper pumping function of the tubular embryonic heart is crucial for survival of higher vertebrate embryos as well as for correct morphogenesis of their hearts [34,35].…”