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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP-
dc.contributor.authorMORALES-QUINONES, Mariana-
dc.contributor.authorI, Francisco Ramirez-Perez-
dc.contributor.authorFOOTE, Christopher A.-
dc.contributor.authorGHIARONE, Thaysa-
dc.contributor.authorFERREIRA-SANTOS, Larissa-
dc.contributor.authorBLOKSGAARD, Maria-
dc.contributor.authorSPENCER, Nicole-
dc.contributor.authorKIMCHI, Eric T.-
dc.contributor.authorMANRIQUE-ACEVEDO, Camila-
dc.contributor.authorPADILLA, Jaume-
dc.contributor.authorMARTINEZ-LEMUS, Luis A.-
dc.identifier.citationHYPERTENSION, v.76, n.2, p.393-403, 2020-
dc.description.abstractIncreased arterial stiffness and vascular remodeling precede and are consequences of hypertension. They also contribute to the development and progression of life-threatening cardiovascular diseases. Yet, there are currently no agents specifically aimed at preventing or treating arterial stiffening and remodeling. Previous research indicates that vascular smooth muscle actin polymerization participates in the initial stages of arterial stiffening and remodeling and that LIMK (LIM kinase) promotes F-actin formation and stabilization via cofilin phosphorylation and consequent inactivation. Herein, we hypothesize that LIMK inhibition is able to prevent vasoconstriction- and hypertension-associated arterial stiffening and inward remodeling. We found that small visceral arteries isolated from hypertensive subjects are stiffer and have greater cofilin phosphorylation than those from nonhypertensives. We also show that LIMK inhibition prevents arterial stiffening and inward remodeling in isolated human small visceral arteries exposed to prolonged vasoconstriction. Using cultured vascular smooth muscle cells, we determined that LIMK inhibition prevents vasoconstrictor agonists from increasing cofilin phosphorylation, F-actin volume, and cell cortex stiffness. We further show that localized LIMK inhibition prevents arteriolar inward remodeling in hypertensive mice. This indicates that hypertension is associated with increased vascular smooth muscle cofilin phosphorylation, cytoskeletal stress fiber formation, and heightened arterial stiffness. Our data further suggest that pharmacological inhibition of LIMK prevents vasoconstriction-induced arterial stiffening, in part, via reductions in vascular smooth muscle F-actin content and cellular stiffness. Accordingly, LIMK inhibition should represent a promising therapeutic means to stop the progression of arterial stiffening and remodeling in hypertension.eng
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/18854-0]-
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HL088105, R01 HL137769, R01 HL142770]-
dc.subjectvascular stiffnesseng
dc.subject.othervascular smooth-muscleeng
dc.subject.otherresistance arterieseng
dc.subject.otheractin polymerizationeng
dc.subject.otheraortic stiffnesseng
dc.subject.othercell stiffnesseng
dc.titleLIMK (LIM Kinase) Inhibition Prevents Vasoconstriction- and Hypertension-Induced Arterial Stiffening and Remodelingeng
dc.rights.holderCopyright LIPPINCOTT WILLIAMS & WILKINSeng
dc.subject.wosPeripheral Vascular Diseaseeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Mariana:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA-, Francisco Ramirez-Perez:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA; Univ Missouri, Dept Biol Engn, Columbia, MO 65211 USA-, Christopher A.:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA-, Thaysa:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA-, Maria:Univ Southern Denmark, Dept Mol Med, Odense, Denmark-, Nicole:Columbia Surg Associates, Columbia, MO USA-, Eric T.:Univ Missouri, Dept Surg, Columbia, MO 65211 USA; Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO USA-, Camila:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA; Univ Missouri, Dept Med, Div Endocrinol Diabet & Metab, Columbia, MO 65211 USA; Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO USA-, Jaume:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA; Univ Missouri, Dept Nutr & Exercise Physiol, Columbia, MO 65211 USA-, Luis A.:Univ Missouri, Dalton Cardiovasc Res Ctr, 1500 Res Pk Dr, Columbia, MO 65211 USA; Univ Missouri, Dept Biol Engn, Columbia, MO 65211 USA; Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA-
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