Biomedical Sciences ETDs

Publication Date

Summer 7-31-2021

Abstract

Hydrogen sulfide (H2S) is a vasodilator primarily produced by cysthathionine

gamma-lyase (CSE) within the vasculature. Previous studies suggest there are

differences in CSE expression and the contribution of H2S to vasodilation in

different sized arteries. This led us to postulate that there are also regional

differences of regulators of H2S-mediated vasodilatory pathways.

This study examined the role of endothelial cell plasma membrane (EC

PM) cholesterol in regulating H2S-induced vasodilation and the role of

intracellular calcium [Ca2+]i in regulating CSE activity in vascular EC. We

hypothesized that CSE activation in EC by receptor-dependent second

messenger signaling enhances H2S production and subsequent H2S-induced

vasodilation, which is limited by EC PM cholesterol.

We found that under basal conditions, 1) EC of large mesenteric arteries

(>300 μm) contain higher PM cholesterol content; 2) large arteries are insensitive

to H2S donor but become sensitive after cholesterol depletion; while the opposite

is seen in small arteries (μm); 4) large and small arteries express TRPV4

and BKCa channels, however; 5) H2S-mediated TRPV4/BKCa vasodilation is

inactive in large arteries but activated by cholesterol depletion. These data

demonstrate EC PM limits H2S-mediated vasodilation and describe innate

regional endothelial differences in mesenteric arteries. Additionally, G proteincoupled

receptor stimulation and increased [Ca2+]i enhances CSE activity in

vascular EC.

Keywords

H2S, Endothelial Cell, Cholesterol, TRPV4, BK, Vasodilation

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Nancy L Kanagy

Second Committee Member

Laura V Gonzalez Bosc

Third Committee Member

Jay S Naik

Fourth Committee Member

Curtis Mowry

Fifth Committee Member

Aleksandr Bir

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