{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:01:38Z","timestamp":1778893298207,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T00:00:00Z","timestamp":1486598400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004348","name":"Stockholm County Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Council Medicine"},{"DOI":"10.13039\/501100000273","name":"Diabetes Research and Wellness Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000273","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Heart and Lung Foundation"},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007464","name":"Torsten S\u00f6derberg Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007464","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Karolinska Institutet\/Stockholm County Council Strategic Cardiovascular Programme"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Diabetes and Vascular Disease Research"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>RhoA\/Rho-associated kinase and arginase are implicated in vascular complications in diabetes. This study investigated whether RhoA\/Rho-associated kinase and arginase inhibition protect from myocardial ischaemia\u2013reperfusion injury in type 1 diabetes and the mechanisms behind these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Rats with streptozotocin-induced type 1 diabetes and non-diabetic rats were subjected to 30\u2009min myocardial ischaemia and 2\u2009h reperfusion after being randomized to treatment with (1) saline, (2) RhoA\/Rho-associated kinase inhibitor hydroxyfasudil, (3) nitric oxide synthase inhibitor N\n                      <jats:sup>G<\/jats:sup>\n                      -monomethyl-l-arginine monoacetate followed by hydroxyfasudil, (4) arginase inhibitor N-omega-hydroxy-nor-l-arginine, (5) N\n                      <jats:sup>G<\/jats:sup>\n                      -monomethyl-l-arginine monoacetate followed by N-omega-hydroxy-nor-l-arginine or (6) N\n                      <jats:sup>G<\/jats:sup>\n                      -monomethyl-l-arginine monoacetate given intravenous before ischaemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Myocardial arginase activity, arginase 2 expression and RhoA\/Rho-associated kinase activity were increased in type 1 diabetes ( p\u2009&lt;\u20090.05). RhoA\/Rho-associated kinase inhibition and arginase inhibition significantly reduced infarct size in diabetic and non-diabetic rats ( p\u2009&lt;\u20090.001). The cardioprotective effects of hydroxyfasudil and N-omega-hydroxy-nor-l-arginine in diabetes were abolished by nitric oxide synthase inhibition. RhoA\/Rho-associated kinase inhibition attenuated myocardial arginase activity in diabetic rats via a nitric oxide synthase\u2013dependent mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Inhibition of either RhoA\/Rho-associated kinase or arginase protects from ischaemia\u2013reperfusion injury in rats with type 1 diabetes via a nitric oxide synthase\u2013dependent pathway. These results suggest that inhibition of RhoA\/Rho-associated kinase and arginase constitutes a potential therapeutic strategy to protect the diabetic heart against ischaemia\u2013reperfusion injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1479164116687935","type":"journal-article","created":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T01:39:11Z","timestamp":1486690751000},"page":"236-245","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of Rho kinase protects from ischaemia\u2013reperfusion injury via regulation of arginase activity and nitric oxide synthase in type 1 diabetes"],"prefix":"10.1177","volume":"14","author":[{"given":"Yahor","family":"Tratsiakovich","sequence":"first","affiliation":[{"name":"Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Cardiology, Karolinska University Hospital, Stockholm, 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