The Effects of Hemodynamic Force on Embryonic Development

Abstract

Blood vessels have long been known to respond to hemodynamic force, and several mechanotransduction pathways have been identified. However, only recently have we begun to understand the effects of hemodynamic force on embryonic development. In this review, we will discuss specific examples illustrating the role of hemodynamic force during the development of the embryo, with particular focus on the development of the vascular system and the morphogenesis of the heart. We will also discuss the important functions served by mechanotransduction and hemodynamic force during placentation, as well as in regulating the maintenance and division of embryonic, hematopoietic, neural, and mesenchymal stem cells. Pathological misregulation of mechanosensitive pathways during pregnancy and embryonic development may contribute to the occurrence of cardiovascular birth defects, as well as to a variety of other diseases, including preeclampsia. Thus, there is a need for future studies focusing on better understanding the physiological effects of hemodynamic force during embryonic development and their role in the pathogenesis of disease.

In vitro microvessels for the study of angiogenesis and thrombosis

“…These include the effects of geometry (42), hydrodynamic stresses, and transport processes (13,43) on the stability of vessels, the progression of angiogenesis, and the interactions of the vessel with blood cells; and the roles of vascular cells from different organs in defining physiological and pathological states specific to those organs (for example, properties of the blood-brain barrier) (44); and the abnormal angiogenic and inflammatory profiles of solid tumors (45) and diabetic tissues (46).…”

Dependence of cardiac trabeculation on neuregulin signaling and blood flow in zebrafish

“…Notably, it is not yet known whether alteration of hemodynamics can affect Neuregulin signal transduction between the endocardium and myocardium (Lai et al, 2010). In addition to the impact of shear forces on the endocardium, the stretch forces experienced during normal ventricular loading could provoke intracellular signaling within the myocardium to drive trabeculation (Culver and Dickinson, 2010). Whether through shear or stretch forces, it is intriguing to consider that hemodynamics could contribute to site selection for the initiation of trabeculation.…”

“…The shear forces generated by circulating blood are known to have a significant impact on heart development (Hove et al, 2003;Vermot et al, 2009;Culver and Dickinson, 2010), and the exposure of the endocardium to shear forces could alter its signaling to the myocardium. Notably, it is not yet known whether alteration of hemodynamics can affect Neuregulin signal transduction between the endocardium and myocardium (Lai et al, 2010).…”

VEGF-Directed Blood Vessel Patterning: From Cells to Organism

“…Endoderm-derived VEGF is required for yolk sac vessel development and patterning, because mosaic loss of endoderm VEGF-A prevents vessel formation in the mesoderm above the mutant endoderm (Damert et al 2002). Yolk sac vessels have an initial phase of sprouting angiogenesis and expand in the lateral plane, then the network undergoes extensive remodeling once blood flow commences (for review, see Culver and Dickinson 2010). It is interesting to speculate that vessel-derived negative cues, such as sFlt-1, may shape VEGF presentation to provide vessel-patterning cues in the lateral plane of the developing yolk sac.…”