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Article: Arterial Wall Stress Induces Phenotypic Switching of Arterial Smooth Muscle Cells in Vascular Remodeling by Activating the YAP/TAZ Signaling Pathway

TitleArterial Wall Stress Induces Phenotypic Switching of Arterial Smooth Muscle Cells in Vascular Remodeling by Activating the YAP/TAZ Signaling Pathway
Authors
KeywordsArterial Smooth Muscle Cells
Cyclic Strain
Shear Stress
Vascular Remodeling
YAP/TAZ
Issue Date2018
PublisherKarger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB
Citation
Cellular Physiology and Biochemistry, 2018, v. 51 n. 2, p. 842-853 How to Cite?
AbstractBackground/Aims: Increasing wall stress or biomechanical stretch experienced by arteries influences the initiation of atherosclerotic lesions. This initiation is mediated by Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway. In this study, the functional roles of YAP/TAZ proteins in the regulation of the stretch-mediated programing of human umbilical arterial smooth muscle cells (HUASMCs) to a proliferative phenotype were examined. Methods: HUASMCs were seeded on a Matrigel-coated silicone chamber and subjected to biomechanical stretch for 24 h after 48 h of growth. YAP/TAZ small interfering RNA was used to specifically knockdown YAP/ TAZ expression in HUASMCs. Results: We observed that YAP/TAZ activation via biomechanical stretching is involved in the regulation of critical aspects of the HUASMC phenotypic switch. YAP/TAZ knockdown significantly attenuated the stretch-induced proliferative and pro-inflammatory phenotypes in HUASMCs. Furthermore, treatment with atorvastatin, an anti-atherosclerotic drug, attenuated the stretch-induced phenotypic switch of HUASMCs from the contractile to synthetic state by suppressing YAP/TAZ expression. Additional investigations demonstrated the role of stretch in inhibiting the Hippo pathway, leading to the activation of PI3-kinase (PI3K) and phosphoinositide dependent kinase (PDK1); the key molecule for the regulation of the PDK1 and Hippo complex interaction was Sav1. These results showed the importance of YAP/TAZ activation, induced by biomechanical stretch, in promoting atheroprone phenotypes in HUASMCs. Conclusion: Taken together, our findings revealed a mechanism by which YAP/TAZ activation contributes to the pathogenesis of atherosclerosis.
Persistent Identifierhttp://hdl.handle.net/10722/293531
ISSN
2017 Impact Factor: 5.5
2015 SCImago Journal Rankings: 1.139
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Y-
dc.contributor.authorCao, W-
dc.contributor.authorCui, J-
dc.contributor.authorYu, Y-
dc.contributor.authorZhao, Y-
dc.contributor.authorShi, J-
dc.contributor.authorWu, J-
dc.contributor.authorXia, Z-
dc.contributor.authorYu, B-
dc.contributor.authorLiu, J-
dc.date.accessioned2020-11-23T08:18:06Z-
dc.date.available2020-11-23T08:18:06Z-
dc.date.issued2018-
dc.identifier.citationCellular Physiology and Biochemistry, 2018, v. 51 n. 2, p. 842-853-
dc.identifier.issn1015-8987-
dc.identifier.urihttp://hdl.handle.net/10722/293531-
dc.description.abstractBackground/Aims: Increasing wall stress or biomechanical stretch experienced by arteries influences the initiation of atherosclerotic lesions. This initiation is mediated by Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway. In this study, the functional roles of YAP/TAZ proteins in the regulation of the stretch-mediated programing of human umbilical arterial smooth muscle cells (HUASMCs) to a proliferative phenotype were examined. Methods: HUASMCs were seeded on a Matrigel-coated silicone chamber and subjected to biomechanical stretch for 24 h after 48 h of growth. YAP/TAZ small interfering RNA was used to specifically knockdown YAP/ TAZ expression in HUASMCs. Results: We observed that YAP/TAZ activation via biomechanical stretching is involved in the regulation of critical aspects of the HUASMC phenotypic switch. YAP/TAZ knockdown significantly attenuated the stretch-induced proliferative and pro-inflammatory phenotypes in HUASMCs. Furthermore, treatment with atorvastatin, an anti-atherosclerotic drug, attenuated the stretch-induced phenotypic switch of HUASMCs from the contractile to synthetic state by suppressing YAP/TAZ expression. Additional investigations demonstrated the role of stretch in inhibiting the Hippo pathway, leading to the activation of PI3-kinase (PI3K) and phosphoinositide dependent kinase (PDK1); the key molecule for the regulation of the PDK1 and Hippo complex interaction was Sav1. These results showed the importance of YAP/TAZ activation, induced by biomechanical stretch, in promoting atheroprone phenotypes in HUASMCs. Conclusion: Taken together, our findings revealed a mechanism by which YAP/TAZ activation contributes to the pathogenesis of atherosclerosis.-
dc.languageeng-
dc.publisherKarger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB-
dc.relation.ispartofCellular Physiology and Biochemistry-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectArterial Smooth Muscle Cells-
dc.subjectCyclic Strain-
dc.subjectShear Stress-
dc.subjectVascular Remodeling-
dc.subjectYAP/TAZ-
dc.titleArterial Wall Stress Induces Phenotypic Switching of Arterial Smooth Muscle Cells in Vascular Remodeling by Activating the YAP/TAZ Signaling Pathway-
dc.typeArticle-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1159/000495376-
dc.identifier.pmid30466081-
dc.identifier.scopuseid_2-s2.0-85057136140-
dc.identifier.hkuros319859-
dc.identifier.volume51-
dc.identifier.issue2-
dc.identifier.spage842-
dc.identifier.epage853-
dc.identifier.isiWOS:000451724100022-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1015-8987-

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