{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:07:57Z","timestamp":1794265677427,"version":"4.9.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p>\n            Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that cleaves angiotensin II to angiotensin 1-7. Recently, it was reported that mice lacking ACE2 (\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice) exhibited reduced cardiac contractility. Because mechanical pressure overload activates the cardiac renin-angiotensin system, we used\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice to analyze the role of ACE2 in the response to pressure overload. Twelve-week-old\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice and wild-type (WT) mice received transverse aortic constriction (TAC) or sham operation. Sham-operated\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice exhibited normal cardiac function and had morphologically normal hearts. In response to TAC,\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice developed cardiac hypertrophy and dilatation. Furthermore, their hearts displayed decreased cardiac contractility and increased fetal cardiac gene induction, compared with WT mice. In response to chronic pressure overload,\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice developed pulmonary congestion and increased incidence of cardiac death compared with WT mice. On a biochemical level, cardiac angiotensin II concentration and activity of mitogen-activated protein (MAP) kinases were markedly increased in\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice in response to TAC. Administration of candesartan, an AT\n            <jats:sub>1<\/jats:sub>\n            subtype angiotensin receptor blocker, attenuated the hypertrophic response and suppressed the activation of MAP kinases in\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice. Activation of MAP kinases in response to angiotensin II was greater in cardiomyocytes isolated from\n            <jats:italic>\n              ACE2\n              <jats:sup>\u2212\/y<\/jats:sup>\n            <\/jats:italic>\n            mice than in those isolated from WT mice. ACE2 plays an important role in dampening the hypertrophic response to pressure overload mediated by angiotensin II. Disruption of this regulatory function may accelerate cardiac hypertrophy and shorten the transition period from compensated hypertrophy to cardiac failure.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000205833.89478.5b","type":"journal-article","created":{"date-parts":[[2006,2,28]],"date-time":"2006-02-28T01:33:51Z","timestamp":1141090431000},"page":"718-726","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":293,"title":["Deletion of Angiotensin-Converting Enzyme 2 Accelerates Pressure Overload-Induced Cardiac Dysfunction by Increasing Local Angiotensin II"],"prefix":"10.1161","volume":"47","author":[{"given":"Koichi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Ohishi","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Katsuya","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Ito","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ikushima","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Kaibe","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Tatara","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Shiota","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumio","family":"Sugano","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Rakugi","sequence":"additional","affiliation":[{"name":"From the Department of Geriatric Medicine (T.K., N.I., M.I., M.K., Y.T., A.S., H.R., T.O.), Osaka University Graduate School of Medicine, Suita; Institute of Medical Science (S.S.), University of Tokyo; and the Otsuka GEN Research Institute (S.T.), Otsuka Pharmaceutical Co. 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