{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:59:29Z","timestamp":1791190769197,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,6,13]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We studied the effects of BNP on preload-dependent myocardial sarcoplasmic reticulum Ca\n            <jats:sup>2+<\/jats:sup>\n            ATPase (SERCA2a) expression. In rabbit isolated muscle strips stretched to high preload and shortening isotonically over 6 hours, the SERCA\/glyceraldehyde phosphate dehydrogenase mRNA ratio was enhanced by 168% (n=8) compared with unloaded preparations (n=8;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001). Recombinant human BNP at a concentration typically found in end-stage HF patients (350 pg\/mL) abolished SERCA upregulation by stretch (n=9;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001 versus BNP free). Inhibition of cyclic guanosine 3\u2032,5\u2032 monophosphate (cGMP)\u2013phosphodiesterase-5 mimicked this effect, whereas inhibition of cGMP-dependent protein kinase restored preload-dependent SERCA upregulation in the presence of recombinant human BNP. Furthermore, in myocardium from human end-stage HF patients undergoing cardiac transplantation (n=15), BNP expression was inversely correlated with SERCA levels. Moreover, among 23 patients treated with left ventricular assist devices, significant SERCA2a recovery occurred in those downregulating BNP.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Our data indicate that preload stimulates SERCA expression. BNP antagonizes this mechanism via guanylyl cyclase-A, cGMP, and cGMP-dependent protein kinase. This novel action of BNP to uncouple preload-dependent SERCA expression may adversely affect contractility in patients with HF.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.608828","type":"journal-article","created":{"date-parts":[[2006,6,6]],"date-time":"2006-06-06T00:58:15Z","timestamp":1149555495000},"page":"2724-2732","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca\n            <sup>2+<\/sup>\n            ATPase Expression"],"prefix":"10.1161","volume":"113","author":[{"given":"Harald","family":"Ko\u0308gler","sequence":"first","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schott","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Toischer","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Milting","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuc Nguyen","family":"Van","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kohlhaas","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Grebe","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Kassner","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Domeier","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Teucher","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Seidler","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Kno\u0308ll","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars S.","family":"Maier","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aly","family":"El-Banayosy","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Ko\u0308rfer","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Hasenfuss","sequence":"additional","affiliation":[{"name":"From Abteilung fu\u0308r Kardiologie, Georg August Universita\u0308t, Go\u0308ttingen (H.K., P.S., K.T., P.N.V., M.K., C.G., E.D., N.T., T.S., R. Kno\u0308ll, L.S.M., G.H.); and Erich und Hanna Klessmann Institut fu\u0308r Kardiovaskula\u0308re Forschung und Entwicklung (H.M., A.K., A.E.-B., R. Ko\u0308rfer), Herz und Diabeteszentrum NRW, Bad Oeynhausen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.88.3.8353861"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000144310.04433.be"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.125.2.652"},{"key":"e_1_3_2_4_2","first-page":"1531","volume":"287","year":"2002","unstructured":"VMAC Investigators. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. 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