{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:30:59Z","timestamp":1784215859494,"version":"3.55.0"},"reference-count":24,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>\n                    Reduced bioavailability of nitric oxide (NO) is accompanied by endothelial dysfunction, which precedes clinical signs of atherosclerosis. The metalloenzyme arginase reciprocally inhibits the formation of NO and available data demonstrate that arginase contributes to reduced bioavailability of NO and increases the formation of reactive oxygen species. Emerging evidence suggests that arginase thereby plays a key role in the pathophysiology of age-associated vascular complications in animal models. However, the role of arginase in elderly human subjects\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    with regard to macrovascular endothelial function is unclear. We hypothesized that arginase inhibition improves endothelial function in an age-dependent manner in elderly healthy subjects. Twenty-one subjects ranging from 48 to 75 years of age were included for evaluation of endothelial function using forearm venous occlusion plethysmography. Endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) were evaluated before and after 2-hour intra-arterial infusion of the arginase inhibitor N\n                    <jats:sup>\u03c9<\/jats:sup>\n                    -hydroxy-nor-L-arginine (nor-NOHA). Baseline EDV, but not EIDV, was inversely correlated with age (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.05, R\u2009=\u2009\u22120.48 and\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.62, R\u2009=\u2009\u22120.14, respectively). The magnitude of the improvement in EDV induced by arginase inhibition was significantly correlated with age (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.05, R\u2009=\u20090.56), whereas EIDV was not (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.25, R\u2009=\u20090.26). Arginase inhibition improves endothelial function in an age-dependent manner in elderly healthy subjects. The results suggest that arginase is a key factor contributing to endothelial dysfunction and may serve as a future pharmacological target for improving endothelial function in elderly subjects.\n                  <\/jats:p>","DOI":"10.1089\/rej.2018.2135","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T05:28:38Z","timestamp":1544419718000},"page":"385-389","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Arginase Inhibition Improves Endothelial Function in an Age-Dependent Manner in Healthy Elderly Humans"],"prefix":"10.1177","volume":"22","author":[{"given":"Ali","family":"Mahdi","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pernow","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"K\u00f6vamees","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,10,17]]},"reference":[{"key":"e_1_3_3_2_2","first-page":"e46","article-title":"Heart disease and stroke statistics\u20142010 update: A report from the American Heart Association","volume":"121","author":"Writing Group M","year":"2010","unstructured":"Writing Group M, , Lloyd-Jones D, , Adams RJ, et al. Heart disease and stroke statistics\u20142010 update: A report from the American Heart Association. Circulation, 2010; 121:e46\u2013e215.","journal-title":"Circulation"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212103272408"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr304"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2009.07.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt036"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000092948.04444.C7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1113\/jphysiol.2006.108993","article-title":"L-Arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin","volume":"574","author":"Holowatz LA","year":"2006","unstructured":"Holowatz LA, , Thompson CS, , Kenney WL. L-Arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin. J Physiol, 2006; 574:573\u2013581.","journal-title":"J Physiol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.140335"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/joim.12461","article-title":"Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels","volume":"279","author":"Kovamees O","year":"2016","unstructured":"Kovamees O, , Shemyakin A, , Eriksson M, , Angelin B, , Pernow J. Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels. 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J Clin Endocrinol Metab, 2016; 101:3952\u20133958.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12785"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/1479164116643916"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1210\/jc.2005-1231","article-title":"Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes","volume":"91","author":"Hermann TS","year":"2006","unstructured":"Hermann TS, , Li W, , Dominguez H, et al. Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes. 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