{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:00:17Z","timestamp":1762430417003},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,2,19]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Hyperhomocysteinemia is a cardiovascular risk factor that is associated with elevation of the nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Using mice transgenic for overexpression of the ADMA-hydrolyzing enzyme dimethylarginine dimethylaminohydrolase-1 (DDAH1), we tested the hypothesis that overexpression of DDAH1 protects from adverse structural and functional changes in cerebral arterioles in hyperhomocysteinemia.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Hyperhomocysteinemia was induced in DDAH1 transgenic (DDAH1 Tg) mice and wild-type littermates using a high methionine\/low folate (HM\/LF) diet. Plasma total homocysteine was elevated approximately 3-fold in both wild-type and DDAH1 Tg mice fed the HM\/LF diet compared with the control diet (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001). Plasma ADMA was approximately 40% lower in DDAH1 Tg mice compared with wild-type mice (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001) irrespective of diet. Compared with the control diet, the HM\/LF diet diminished endothelium-dependent dilation to 10 \u03bcmol\/L acetylcholine in cerebral arterioles of both wild-type (12\u00b12 versus 29\u00b13%;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001) and DDAH1 Tg (14\u00b13 versus 28\u00b12%;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001) mice. Responses to 10 \u03bcmol\/L papaverine, a direct smooth muscle dilator, were impaired with the HM\/LF diet in wild-type mice (30\u00b13 versus 45\u00b15%;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) but not DDAH1 Tg mice (45\u00b17 versus 48\u00b16%). DDAH1 Tg mice also were protected from hypertrophy of cerebral arterioles (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) but not from accelerated carotid artery thrombosis induced by the HM\/LF diet.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Overexpression of DDAH1 protects from hyperhomocysteinemia-induced alterations in cerebral arteriolar structure and vascular muscle function.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.200360","type":"journal-article","created":{"date-parts":[[2009,12,18]],"date-time":"2009-12-18T07:56:20Z","timestamp":1261122980000},"page":"551-558","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Overexpression of Dimethylarginine Dimethylaminohydrolase Protects Against Cerebral Vascular Effects of Hyperhomocysteinemia"],"prefix":"10.1161","volume":"106","author":[{"given":"Roman N.","family":"Rodionov","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayan","family":"Dayoub","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia M.","family":"Lynch","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katina M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff W.","family":"Stevens","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl J.","family":"Murry","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masumi","family":"Kimoto","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erland","family":"Arning","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Cooke","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary L.","family":"Baumbach","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank M.","family":"Faraci","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven R.","family":"Lentz","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (R.N.R., K.M.W., J.W.S., F.M.F., S.R.L.), Neurosurgery (H.D.), Pharmacology (C.M.L., F.M.F.), and Pathology (G.L.B.), University of Iowa Carver College of Medicine, Iowa City; Department of Medicine III (R.N.R.), University Center for Vascular Medicine, Angiology Division, University Hospital Carl Gustav Carus, Technical University of Dresden, Germany; University of Iowa College of Pharmacy (D.J.M.), Iowa City; Department of Nutritional Science (M.K.),..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.16.2015"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01141.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01364.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.5.565"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055227"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060900"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.10.1163"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-014654"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.299.17.2027"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.108.164830"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.104.21.2569"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2006.03.006"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01348.2007"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000101924.04515.2e"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.490631"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.037036"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000219615.88323.b4"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000229598.55602.17"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-09-3078"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.20.7.1704"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0801(199902)13:1<81::AID-BMC762>3.0.CO;2-U"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5575"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/117.2.237"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000131749.81508.18"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118497"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000041408.64867.1d"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.68.2.1991342"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2003.00482.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000189559.87328.e4"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1771"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/84.4.781"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2006.08.004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603606200"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02309-2"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.108.166421"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118771"},{"key":"e_1_3_2_37_2","first-page":"A22.","volume":"45","year":"2007","unstructured":"Dayal S, Baumbach GL, Arning E, Bottiglieri T, Faraci FM, Lentz SR. Deficiency of superoxide dismutase-1 sensitizes to endothelial dysfunction and hypertrophy of cerebral arterioles in hyperhomocysteinemic mice. Clin Chem Lab Med. 2007; 45: A22. 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