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035 a| (Sirsi) o1506074635;

035 a| (OCoLC)1506074635;

049 a| EREE;

096 a| WG 500;

100 1 a| Williams, Madison D.,e| author.;

245 10 a| Novel GPCR mechanisms of phenotypic control in vascular smooth muscle /c| by Madison D. Williams.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2024.;

300 a| 1 online resource (124 pages) :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| application/pdfc| 8.57 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 c| East Carolina Universityd| 2024.;

502 a| Presented to the Faculty of the Department of Physiology;

500 a| Advisor: David Tulis;

500 a| Title from PDF t.p. (viewed February 24, 2026).;

520 3 a| Cardiovascular disease (CVD) is a significant global health concern and the number one cause of morbidity and mortality in the US and worldwide. Ischemia and resulting tissue hypoxia and acidosis are important contributors to CVD development and progression. G protein-coupled receptors (GPCRs) are seven transmembrane receptors with established functions in cardiovascular (patho)physiology. Phenotypic switching of vascular smooth muscle (VSM) from a contractile, quiescent state to a noncontractile, proliferative state is a common feature of CVD. Two GPCRs, protease-activated receptor 2 (PAR2) and GPR68, have capacity to control cell proliferation in various tissues, but their role(s) in VSM cell proliferation and phenotypic control remain unclear. The purpose of this project was to determine how PAR2 and GPR68 independently control VSM cell growth and phenotype. Findings revealed that PAR2 controls VSM cell growth in a PKA/MEK1/2 and phenotype-dependent manner, while GPR68 inhibits VSM cell growth through Rap1A. Proteomics analysis revealed wide-ranging effects of GPR68 on VSM phenotype including modulation of extracellular matrix, actin-binding, and contractile proteins. Our findings highlight novel mechanisms of PAR2 and GPR68 in VSM cell growth and phenotypic control and offer evidence that they might be important targets for treatment of deleterious phenotypic switching of VSM in CVD.;

504 a| Includes bibliographical references.;

650 2 a| Muscle, Smooth, Vascular.;

653 a| cardiovascular disease;

653 a| vascular smooth muscle;

653 a| PAR2;

653 a| GPR68;

653 a| phenotypic switching;

653 a| cell proliferation;

700 1 a| Tulis, David,e| degree supervisor.;

710 2 a| East Carolina University.b| Department of Physiology.;

830 0 a| ECU Brody School of Medicine dissertation.;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/13857;

949 o| wjh;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 6560813;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 6560813-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 3/10/2025x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 6560813-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 3/10/2025x| ETDz| HERESOURCE;

Novel GPCR mechanisms of phenotypic control in vascular smooth muscle / by Madison D. Williams.

Author/creator	Williams, Madison D. author.
Other author	Tulis, David, degree supervisor.
Other author	East Carolina University. Department of Physiology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2024.
Description	1 online resource (124 pages) : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Muscle, Smooth, Vascular.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation.
Summary	Cardiovascular disease (CVD) is a significant global health concern and the number one cause of morbidity and mortality in the US and worldwide. Ischemia and resulting tissue hypoxia and acidosis are important contributors to CVD development and progression. G protein-coupled receptors (GPCRs) are seven transmembrane receptors with established functions in cardiovascular (patho)physiology. Phenotypic switching of vascular smooth muscle (VSM) from a contractile, quiescent state to a noncontractile, proliferative state is a common feature of CVD. Two GPCRs, protease-activated receptor 2 (PAR2) and GPR68, have capacity to control cell proliferation in various tissues, but their role(s) in VSM cell proliferation and phenotypic control remain unclear. The purpose of this project was to determine how PAR2 and GPR68 independently control VSM cell growth and phenotype. Findings revealed that PAR2 controls VSM cell growth in a PKA/MEK1/2 and phenotype-dependent manner, while GPR68 inhibits VSM cell growth through Rap1A. Proteomics analysis revealed wide-ranging effects of GPR68 on VSM phenotype including modulation of extracellular matrix, actin-binding, and contractile proteins. Our findings highlight novel mechanisms of PAR2 and GPR68 in VSM cell growth and phenotypic control and offer evidence that they might be important targets for treatment of deleterious phenotypic switching of VSM in CVD.
General note	Advisor: David Tulis
General note	Title from PDF t.p. (viewed February 24, 2026).
Dissertation note	East Carolina University 2024.
Dissertation note	Presented to the Faculty of the Department of Physiology
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Novel GPCR mechanisms of phenotypic control in vascular smooth muscle / by Madison D. Williams.

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