Dataset Information

ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

ABSTRACT: Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response.

SUBMITTER: Beckers CM

PROVIDER: S-EPMC4606924 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

Beckers Cora M L CM Knezevic Nebojsa N Valent Erik T ET Tauseef Mohammad M Krishnan Ramaswamy R Rajendran Kavitha K Hardin C Corey CC Aman Jurjan J van Bezu Jan J Sweetnam Paul P van Hinsbergh Victor W M VW Mehta Dolly D van Nieuw Amerongen Geerten P GP

Vascular pharmacology 20150411

Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated t ...[more]

PMID: 25869521

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Dataset Information

ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

Publications

ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

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