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AuthorTedy, Sawma
AuthorShaito, Abdullah
AuthorNajm, Nicolas
AuthorSidani, Munir
AuthorOrekhov, Alexander
AuthorEl-Yazbi, Ahmed F.
AuthorIratni, Rabah
AuthorEid, Ali H.
Available date2022-09-06T05:26:25Z
Publication Date2022-10-31
Publication NameAtherosclerosis
Identifierhttp://dx.doi.org/10.1016/j.atherosclerosis.2022.08.012
CitationSawma T, Shaito A, Najm N, Sidani M, Orekhov A, El-Yazbi AF, Iratni R, Eid AH. Role of RhoA and Rho-associated kinase in phenotypic switching of vascular smooth muscle cells: Implications for vascular function. Atherosclerosis. 2022 Aug 15;358:12-28. doi: 10.1016/j.atherosclerosis.2022.08.012.
ISSN00219150
URIhttps://www.sciencedirect.com/science/article/pii/S0021915022013958
URIhttp://hdl.handle.net/10576/33698
AbstractCardiovascular disease (CVD) continues to be the primary cause of global mortality. Vascular smooth muscle cells (VSMCs) are integral components of vascular structure and function, evident by their vital roles in modulating blood flow and pressure. Such roles exist due to the differentiated contractile phenotype of VSMCs. However, VSMCs may switch to a dedifferentiated, proliferative synthetic phenotype in a phenomenon known as phenotypic switching. This switch involves dramatic changes in VSMC migration, proliferation, gene expression programs, differentiation, cellular stiffness and extracellular matrix (ECM) deposition. In this review, we explore the role of the small GTPase Rho and its effector, Rho-associated kinase (ROCK), in phenotypic switching as well as apoptotic pathways in VSMCs. We critically dissect how RhoA promotes cell migration and proliferation as well as its role in modulating the expression of a battery of VSMC marker proteins. We also discuss how RhoA modulates apoptosis, induces dedifferentiation, increases vascular stiffness, or modifies ECM accumulation. These alterations in VSMC phenotypes contribute to multiple vascular dysfunctions, including hypertension and atherosclerosis. Understanding the molecular underpinnings and the signaling pathways involved in these altered phenotypes may provide novel avenues of drug design and other therapeutic interventions for the management of CVDs.
Languageen
PublisherElsevier
SubjectRhoA
Rho kinase
Vascular smooth muscle cell
Phenotypic switch
Cardiovascular disease
Apoptosis
TitleRole of RhoA and Rho-associated kinase in phenotypic switching of vascular smooth muscle cells: Implications for vascular function
TypeArticle Review
Pagination12-28
Volume Number358
dc.accessType Open Access


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