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Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA\/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P\u00a0=\u00a00.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P\u00a0&amp;lt;\u00a00.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries {Masson's trichrome (MT) 69.7% [95% confidence interval (CI): 67.8\u201371.7]; picrosirius red 68.6% [95% CI: 64.4\u201372.8]} vs. controls [MT 64.9% (95% CI: 59.4\u201370.3) (P\u00a0=\u00a00.028); picrosirius red 60.1% (95% CI: 55.4\u201364.8), (P\u00a0=\u00a00.029)]. Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9\u201349.3) vs. controls (10.0%; 95% CI: 4.4\u201315.6) (P\u00a0&amp;lt;\u00a00.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvad025","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T02:20:51Z","timestamp":1680747651000},"page":"371-386","source":"Crossref","is-referenced-by-count":20,"title":["Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-5474","authenticated-orcid":false,"given":"Robert A","family":"Sykes","sequence":"first","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , UK"},{"name":"West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5158-9263","authenticated-orcid":false,"given":"Karla 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