{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T23:35:58Z","timestamp":1780443358123,"version":"3.54.1"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,11,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Kallistatin exerts beneficial effects on organ injury by inhibiting oxidative stress and inflammation. However, the role of kallistatin in atherosclerosis is largely unknown. Here, we investigated the role and mechanisms of kallistatin in patients with coronary artery disease (\n              <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content>\n              ), atherosclerotic plaques of apoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, and endothelial activation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Plasma kallistatin levels were analyzed in 453 patients at different stages of\n              <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content>\n              . Kallistatin levels were significantly lower in patients with\n              <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content>\n              and negatively associated with\n              <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content>\n              severity and oxidative stress. Human kallistatin\n              <jats:styled-content style=\"fixed-case\">cDNA<\/jats:styled-content>\n              in an adenoviral vector was injected intravenously into apoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice after partial carotid ligation, with or without nitric oxide synthase inhibitor (N\n              <jats:sup>\u03c9<\/jats:sup>\n              \u2010nitro\u2010L\u2010arginine methyl ester) or sirtuin 1 inhibitor (nicotinamide). Kallistatin gene delivery significantly reduced macrophage deposition, oxidative stress, and plaque volume in the carotid artery, compared with control adenoviral injection. Kallistatin administration increased endothelial nitrous oxide synthase, sirtuin 1, interleukin\u201010, superoxide dismutase 2, and catalase expression in carotid plaques. The beneficial effects of kallistatin in mice were mitigated by N\n              <jats:sup>\u03c9<\/jats:sup>\n              \u2010nitro\u2010L\u2010arginine methyl ester or nicotinamide. Furthermore, human kallistatin protein suppressed tumor necrosis factor\u2010\u03b1\u2013induced\n              <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\n              oxidase activity and increased endothelial nitrous oxide synthase and sirtuin 1 expression in cultured human endothelial cells. These effects were also abolished by N\n              <jats:sup>\u03c9<\/jats:sup>\n              \u2010nitro\u2010L\u2010arginine methyl ester or nicotinamide.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              This was the first study to demonstrate that reduced plasma kallistatin levels in patients are associated with\n              <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content>\n              severity and oxidative stress. Kallistatin treatment prevents carotid atherosclerotic plaque formation in mice by stimulating the sirtuin 1\/endothelial nitrous oxide synthase pathway. These findings indicate the potential protective effects of kallistatin on atherosclerosis in human subjects and mouse models.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.009562","type":"journal-article","created":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T20:51:35Z","timestamp":1544993495000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Reduced Plasma Kallistatin Is Associated With the Severity of Coronary Artery Disease, and Kallistatin Treatment Attenuates Atherosclerotic Plaque Formation in Mice"],"prefix":"10.1161","volume":"7","author":[{"given":"Yuyu","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Medical School of Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Medical School of Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Medical School of Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Medical School of Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of South Carolina Charleston SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youming","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of South Carolina Charleston SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genshan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Medical School of Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Medical School of Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of South Carolina Charleston SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical University of South Carolina Charleston SC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu299"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.008720"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2015.07.007"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.7.898"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306301"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23415"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2015.00029"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07861"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.152330"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0185"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.108514"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.85"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.331"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(83)80105-2"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.1.451"},{"key":"e_1_3_1_17_2","first-page":"641","article-title":"Analysis of in\u00a0situ and ex\u00a0vivo \u03b1V\u03b23 integrin expression during experimental carotid atherogenesis","volume":"7","author":"Yao Y","year":"2012","unstructured":"Yao Y, Jiang Y, Sheng Z, Zhang Y, An Y, Yan F, Ma G, Liu N, Teng G, Cheng Z. 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