Notch signaling regulates arterial vasoreactivity through opposing functions of Jagged1 and Dll4 in the vessel wall

American Journal of Physiology. Heart and Circulatory Physiology
Sanchita BasuAaron Proweller

Abstract

Functional interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) in the arterial wall are necessary for controlling vasoreactivity that underlies vascular resistance and tone. Key signaling pathways converge on the phosphorylation of myosin light chain (p-MLC), the molecular signature of force production in SMCs, through coordinating the relative activities of myosin light chain kinase (MLCK) and myosin phosphatase (MP). Notch signaling in the vessel wall serves critical roles in arterial formation and maturation and has been implicated in arterial vasoregulation. In this report, we hypothesized that Notch signaling through ligands Jagged1 (in SMCs) and delta-like protein-4 (Dll4; in ECs) regulates vasoreactivity via homotypic (SMC-SMC) and heterotypic (EC-SMC) cell interactions. Using ligand induction assays, we demonstrated that Jagged1 selectively induced smooth muscle MLCK gene expression and p-MLC content while inhibiting MP function (i.e., increased Ca2+ sensitization) in a Rho kinase II-dependent manner. Likewise, selective deficiency of smooth muscle Jagged1 in mice resulted in MLCK and p-MLC loss, reduced Ca2+ sensitization, and impaired arterial force generation measured by myography. In contrast...Continue Reading

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Sep 29, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Miranda E Good, Brant E Isakson
Oct 13, 2020·Tissue Engineering. Part B, Reviews·Kathleen Zohorsky, Kibret Mequanint

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PCR
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glycosylation

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ImageJ
GraphPad Prism

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