{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:53:23Z","timestamp":1792457603870,"version":"4.5.0"},"reference-count":101,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 DK132948"],"award-info":[{"award-number":["RO1 DK132948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The small GTPase RhoA and its downstream effector Rho-kinase (ROCK) have emerged as pivotal regulators of vascular smooth muscle cell (VSMC) contraction, endothelial function, and vascular remodeling. Activation of the RhoA\/ROCK pathway enhances calcium (Ca2+) sensitivity by inhibiting myosin light chain phosphatase (MLCP), thereby promoting sustained vascular tone independent of intracellular Ca2+ levels. In endothelial cells (ECs), RhoA\/ROCK signaling contributes to nitric oxide (NO) dysregulation, oxidative stress, cytoskeletal reorganization, and inflammatory activation. Cumulative evidence implicates this pathway in the development and progression of hypertension and other cardiovascular diseases, where maladaptive vascular remodeling, VSMC proliferation, and endothelial dysfunction drive increased vascular resistance. Translational studies have identified ROCK inhibitors and indirect modulators such as statins as promising therapeutic strategies. This review integrates recent mechanistic insights into RhoA\/ROCK regulation of vascular function with clinical and translational perspectives on targeting this pathway in hypertension.<\/jats:p>","DOI":"10.3390\/biom15111607","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:04:07Z","timestamp":1763388247000},"page":"1607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["RhoA\/Rho-Kinase Signaling in Vascular Smooth Muscle and Endothelium: Mechanistic Insights and Translational Implications in Hypertension"],"prefix":"10.3390","volume":"15","author":[{"given":"Stephanie","family":"Randar","sequence":"first","affiliation":[{"name":"Cardiovascular Translational Research Center, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-4371","authenticated-orcid":false,"given":"Diana L.","family":"Silva-Velasco","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research Center, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"},{"name":"Department of Biomedical Engineering Molinaroli, Swearingen Engineering Center, College of Engineering and Computing, University of South Carolina, 301 Main Street, Room 3A47, Columbia, SC 29208, USA"},{"name":"Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-2081","authenticated-orcid":false,"given":"Fernanda","family":"Priviero","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research Center, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"},{"name":"Department of Biomedical Engineering Molinaroli, Swearingen Engineering Center, College of Engineering and Computing, University of South Carolina, 301 Main Street, Room 3A47, Columbia, SC 29208, USA"},{"name":"Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9403-305X","authenticated-orcid":false,"given":"R. Clinton","family":"Webb","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research Center, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"},{"name":"Department of Biomedical Engineering Molinaroli, Swearingen Engineering Center, College of Engineering and Computing, University of South Carolina, 301 Main Street, Room 3A47, Columbia, SC 29208, USA"},{"name":"Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, 6311 Garners Ferry Road, Building 1, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Durante, A., Mazzapicchi, A., and Baiardo Redaelli, M. (2024). Systemic and Cardiac Microvascular Dysfunction in Hypertension. Int. J. Mol. 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