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Hemodynamic force is required for vascular smooth muscle cell recruitment to blood vessels during mouse embryonic development.

Abstract：

:Blood vessel maturation, which is characterized by the investment of vascular smooth muscle cells (vSMCs) around developing blood vessels, begins when vessels remodel into a hierarchy of proximal arteries and proximal veins that branch into smaller distal capillaries. The ultimate result of maturation is formation of the tunica media-the middlemost layer of a vessel that is composed of vSMCs and acts to control vessel integrity and vascular tone. Though many studies have implicated the role of various signaling molecules in regulating maturation, no studies have determined a role for hemodynamic force in the regulation of maturation in the mouse. In the current study, we provide evidence that a hemodynamic force-dependent mechanism occurs in the mouse because reduced blood flow mouse embryos exhibited a diminished or absent coverage of vSMCs around vessels, and in normal-flow embryos, extent of coverage correlated to the amount of blood flow that vessels were exposed to. We also determine that the cellular mechanism of force-induced maturation was not by promoting vSMC differentiation/proliferation, but instead involved the recruitment of vSMCs away from neighboring low-flow distal capillaries towards high-flow vessels. Finally, we hypothesize that hemodynamic force may regulate expression of specific signaling molecules to control vSMC recruitment to high-flow vessels, as reduction of flow results in the misexpression of Semaphorin 3A, 3F, 3G, and the Notch target gene Hey1, all of which are implicated in controlling vessel maturation. This study reveals another role for hemodynamic force in regulating blood vessel development of the mouse, and opens up a new model to begin elucidating mechanotransduction pathways regulating vascular maturation.

journal_name

Mech Dev

journal_title

Mechanisms of development

authors

Padget RL,Mohite SS,Hoog TG,Justis BS,Green BE,Udan RS

doi

10.1016/j.mod.2019.02.002

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

8-19

eissn

0925-4773

issn

1872-6356

pii

S0925-4773(18)30120-5

journal_volume

156

pub_type

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Hemodynamic force is required for vascular smooth muscle cell recruitment to blood vessels during mouse embryonic development.