scholarly journals Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR

2018 ◽  
Author(s):  
Nabil J. Alkayed ◽  
Zhiping Cao ◽  
Zu Yuan Qian ◽  
Shanthi Nagarajan ◽  
Xuehong Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Vascular Resistance ◽  
Muscle Cell ◽  
Cell Receptor ◽  
Zinc Ion ◽  
Mechanisms Of Action ◽  
Coronary Vascular Resistance ◽  
Acid Metabolites ◽  
G Protein Coupled

AbstractArachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We identified G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor antagonistically regulated by two endogenous eicosanoids: 15-HETE, which stimulates GPR39 to increase mVSMC intracellular calcium and augment microvascular CVR, and 14,15-EET, which inhibits these actions. Furthermore, zinc ion acts as an allosteric modulator of GPR39 to potentiate the efficacy of the two ligands. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease, and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.One Sentence SummaryGPR39 is a microvascular smooth muscle cell receptor regulated by two vasoactive eicosanoids with opposing actions.

scholarly journals Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR

2021 ◽  
Author(s):  
Nabil Alkayed ◽  
Zhiping Cao ◽  
Zu Yuan Qian ◽  
Shanthi Nagarajan ◽  
Carmen Methner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Vascular Resistance ◽  
Muscle Cell ◽  
Cell Receptor ◽  
Zinc Ion ◽  
Coronary Vascular Resistance ◽  
Wild Type ◽  
Acid Metabolites ◽  
G Protein Coupled

Abstract Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We identified G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor antagonistically regulated by two endogenous eicosanoids: 15-HETE, which stimulates GPR39 to increase mVSMC intracellular calcium and augment microvascular CVR, and 14,15-EET, which inhibits these actions. Furthermore, zinc ion acts as an allosteric modulator of GPR39 to potentiate the efficacy of the two ligands. Finally, GPR39 knockout mice are protected from myocardial ischemia compared to wild-type littermates. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease, and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease. One Sentence Summary: GPR39 is a microvascular smooth muscle cell receptor regulated by two vasoactive eicosanoids with opposing actions.

scholarly journals The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca2+Handling

2013 ◽  
Vol 50 (5) ◽  
pp. 421-429 ◽  
Author(s):  
Anders Holm ◽  
Per Hellstrand ◽  
Björn Olde ◽  
Daniel Svensson ◽  
L.M. Fredrik Leeb-Lundberg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
G Protein ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

scholarly journals Human Cytomegalovirus-Encoded G Protein-Coupled Receptor US28 Mediates Smooth Muscle Cell Migration through Gα12

2004 ◽  
Vol 78 (15) ◽  
pp. 8382-8391 ◽  
Author(s):  
Ryan M. Melnychuk ◽  
Daniel N. Streblow ◽  
Patricia P. Smith ◽  
Alec J. Hirsch ◽  
Dora Pancheva ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
G Protein ◽  
G Proteins ◽  
Muscle Cell ◽  
Human Cytomegalovirus ◽  
Signaling Molecules ◽  
Cellular Migration ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

ABSTRACT Coupling of G proteins to ligand-engaged chemokine receptors is the paramount event in G-protein-coupled receptor signal transduction. Previously, we have demonstrated that the human cytomegalovirus-encoded chemokine receptor US28 mediates human vascular smooth muscle cell (SMC) migration in response to either RANTES or monocyte chemoattractant protein 1. In this report, we identify the G proteins that couple with US28 to promote vascular SMC migration and identify other signaling molecules that play critical roles in this process. US28-mediated cellular migration was enhanced with the expression of the G-protein subunits Gα12 and Gα13, suggesting that US28 may functionally couple to these G proteins. In correlation with this observation, US28 was able to activate RhoA, a downstream effector of Gα12 and Gα13 in cell types with these G proteins but not in those without them and activation of RhoA was dependent on US28 stimulation with RANTES. In addition, inactivation of RhoA or the RhoA-associated kinase p160ROCK with a dominant-negative mutant of RhoA or the small molecule inhibitor Y27632, respectively, abrogated US28-induced SMC migration. The data presented here suggest that US28 functionally signals through Gα12 family G proteins and RhoA in a ligand-dependent manner and these signaling molecules are important for the ability of US28 to induce cellular migration.

scholarly journals The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification

2018 ◽  
Vol 115 (10) ◽  
pp. 1557-1566 ◽  
Author(s):  
Miguel Carracedo ◽  
Gonzalo Artiach ◽  
Anna Witasp ◽  
Joan Clària ◽  
Mattias Carlström ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
G Protein ◽  
Vascular Calcification ◽  
Muscle Cell ◽  
Cell Phenotype ◽  
Omega 3 ◽  
Smooth Muscle Cell Phenotype ◽  
G Protein Coupled

Abstract Aims Vascular calcification, a marker of increased cardiovascular risk, is an active process orchestrated by smooth muscle cells. Observational studies indicate that omega-3 fatty acids protect against vascular calcification, but the mechanisms are unknown. The G-protein coupled receptor ChemR23 transduces the resolution of inflammation induced by the omega-3-derived lipid mediator resolvin E1. ChemR23 also contributes to osteoblastic differentiation of stem cells and bone formation, but its role in vascular calcification is unknown. The aim of this study was to establish the role of ChemR23 in smooth muscle cell fate and calcification Methods and results Gene expression analysis in epigastric arteries derived from patients with chronic kidney disease and vascular calcification revealed that ChemR23 mRNA levels predicted a synthetic smooth muscle cell phenotype. Genetic deletion of ChemR23 in mice prevented smooth muscle cell de-differentiation. ChemR23-deficient smooth muscle cells maintained a non-synthetic phenotype and exhibited resistance to phosphate-induced calcification. Moreover, ChemR23-deficient mice were protected against vitamin D3-induced vascular calcification. Resolvin E1 inhibited smooth muscle cell calcification through ChemR23. Introduction of the Caenorhabditis elegans Fat1 transgene, leading to an endogenous omega-3 fatty acid synthesis and hence increased substrate for resolvin E1 formation, significantly diminished the differences in phosphate-induced calcification between ChemR23+/+ and ChemR23−/− mice. Conclusion This study identifies ChemR23 as a previously unrecognized determinant of synthetic and osteoblastic smooth muscle cell phenotype, favouring phosphate-induced vascular calcification. This effect may be of particular importance in the absence of ChemR23 ligands, such as resolvin E1, which acts as a calcification inhibitor under hyperphosphatic conditions.

Remodelling of stem villous arteries due to smooth muscle cell dedifferentiation mediates increased vascular resistance of IUGR

Placenta ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. A76
Author(s):  
Tereza Cindrova-Davies ◽  
Liangjian Lu ◽  
John Kingdom ◽  
Graham J. Burton
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Vascular Resistance ◽  
Muscle Cell ◽  
Cell Dedifferentiation

G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60c-src and p21ras

1997 ◽  
Vol 272 (6) ◽  
pp. C2019-C2030 ◽  
Author(s):  
B. Schieffer ◽  
H. Drexler ◽  
B. N. Ling ◽  
M. B. Marrero
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
G Protein ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
G Protein Coupled Receptors ◽  
Smooth Muscle Cell Proliferation ◽  
G Protein Coupled

The binding of vasoactive peptides to their respective G protein-coupled receptors has been implicated in the pathogenesis of vascular smooth muscle cell proliferation, leading to the development of hypertension, arteriosclerosis, and restenosis after vascular injury. We previously showed that the cytosolic tyrosine kinase pp60c-src is crucial for angiotensin II (ANG II)-induced activation of the protooncogene p21ras. Therefore, we investigated the role of pp60c-src and p21ras in rat aortic smooth muscle cell proliferation induced by several G protein-coupled receptors. ANG II, endothelin-1, or thrombin increased cell proliferation and DNA synthesis. Electroporation of anti-pp60c-src antibodies into cells abolished proliferation in response to these G protein-coupled receptor ligands but not in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, electroporation of anti-p21ras antibody completely blocked DNA synthesis and cell proliferation in response to ANG II, endothelin-1, thrombin, and PDGF-BB. Our data indicate that the pp60c-src tyrosine kinase is necessary and specific for vascular smooth muscle cell proliferation and DNA synthesis in response to G protein-coupled receptors but not classic growth factor receptors.

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