{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:58:51Z","timestamp":1792022331837,"version":"4.4.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,5,25]]},"abstract":"<jats:p>\n                    <jats:italic>Abstract<\/jats:italic>\n                    \u2014Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesized that HO would be important for the regulation of blood pressure and ischemic injury. We studied chronic renovascular hypertension in mice deficient in the inducible isoform of HO (HO-1) using a one kidney\u2013one clip (1K1C) model of disease. Systolic blood pressure was not different between wild-type (HO-1\n                    <jats:sup>+\/+<\/jats:sup>\n                    ), heterozygous (HO-1\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ), and homozygous null (HO-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice at baseline. After 1K1C surgery, HO-1\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice developed hypertension (140\u00b12 mm Hg) and cardiac hypertrophy (cardiac weight index of 5.0\u00b10.2 mg\/g) compared with sham-operated HO-1\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice (108\u00b15 mm Hg and 4.1\u00b10.1 mg\/g, respectively). However, 1K1C produced more severe hypertension (164\u00b12 mm Hg) and cardiac hypertrophy (6.9\u00b10.6 mg\/g) in HO-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. HO-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice also experienced a high rate of death (56%) within 72 hours after 1K1C surgery compared with HO-1\n                    <jats:sup>+\/+<\/jats:sup>\n                    (25%) and HO-1\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    (28%) mice. Assessment of renal function showed a significantly higher plasma creatinine in HO-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice compared with HO-1\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice. Histological analysis of kidneys from 1K1C HO-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice revealed extensive ischemic injury at the corticomedullary junction, whereas kidneys from sham HO-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and 1K1C HO-1\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice appeared normal. Taken together, these data suggest that chronic deficiency of HO-1 does not alter basal blood pressure; however, in the 1K1C model an absence of HO-1 leads to more severe renovascular hypertension and cardiac hypertrophy. Moreover, renal artery clipping leads to an acute increase in ischemic damage and death in the absence of HO-1.\n                  <\/jats:p>","DOI":"10.1161\/hh1001.091521","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T14:32:49Z","timestamp":1190989969000},"page":"1088-1094","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":78,"title":["Exacerbation of Chronic Renovascular Hypertension and Acute Renal Failure in Heme Oxygenase-1\u2013Deficient Mice"],"prefix":"10.1161","volume":"88","author":[{"given":"Philippe","family":"Wiesel","sequence":"first","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand P.","family":"Patel","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irvith M.","family":"Carvajal","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pellacani","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Maemura","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"DiFonzo","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut G.","family":"Rennke","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Layne","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaw-Fang","family":"Yet","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-En","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. L., M.A.P.), the Cardiovascular (S.F.-Y., M.-E.L.) and Pulmonary and Critical Care Divisions (M.D.L., M.A.P.), and the Department of Pathology (H.G.R.), Brigham and Women\u2019s Hospital, Boston, Mass; the Department of Medicine (A.P., M.D.L., S.-F.Y., M.-E.L., M.A.P.), Harvard Medical School, Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Perrella","sequence":"additional","affiliation":[{"name":"From the Program of Developmental Cardiovascular Biology (P.W., A.P.P., I.M.C., Z.Y.W., A.P., K.M., N.D., M.D.L., S.-F. Y., M.-E. 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