{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:00:09Z","timestamp":1772164809061,"version":"3.50.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,1,20]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Soluble guanylyl cyclase (sGC) generates cyclic guanosine monophophate (cGMP) upon activation by nitric oxide (NO). Cardiac NO\u2013sGC-cGMP signaling blunts cardiac stress responses, including pressure-overload\u2013induced hypertrophy. The latter itself depresses signaling through this pathway by reducing NO generation and enhancing cGMP hydrolysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>We tested the hypothesis that the sGC response to NO also declines with pressure-overload stress and assessed the role of heme-oxidation and altered intracellular compartmentation of sGC as potential mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      C57BL\/6 mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and dysfunction. NO-stimulated sGC activity was markedly depressed, whereas NO- and heme-independent sGC activation by BAY 60\u20132770 was preserved. Total sGC\u03b1\n                      <jats:sub>1<\/jats:sub>\n                      and \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      expression were unchanged by TAC; however, sGC\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      subunits shifted out of caveolin-enriched microdomains. NO-stimulated sGC activity was 2- to 3-fold greater in Cav3-containing lipid raft versus nonlipid raft domains in control and 6-fold greater after TAC. In contrast, BAY 60\u20132770 responses were &gt;10 fold higher in non-Cav3 domains with and without TAC, declining about 60% after TAC within each compartment. Mice genetically lacking Cav3 had reduced NO- and BAY-stimulated sGC activity in microdomains containing Cav3 for controls but no change within non\u2013Cav3-enriched domains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Pressure overload depresses NO\/heme-dependent sGC activation in the heart, consistent with enhanced oxidation. The data reveal a novel additional mechanism for reduced NO-coupled sGC activity related to dynamic shifts in membrane microdomain localization, with Cav3-microdomains protecting sGC from heme-oxidation and facilitating NO responsiveness. Translocation of sGC out of this domain favors sGC oxidation and contributes to depressed NO-stimulated sGC activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.111.259242","type":"journal-article","created":{"date-parts":[[2011,11,18]],"date-time":"2011-11-18T01:12:05Z","timestamp":1321578725000},"page":"295-303","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["Pressure-Overload\u2013Induced Subcellular Relocalization\/Oxidation of Soluble Guanylyl Cyclase in the Heart Modulates Enzyme Stimulation"],"prefix":"10.1161","volume":"110","author":[{"given":"Emily J.","family":"Tsai","sequence":"first","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchuan","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norimichi","family":"Koitabashi","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djahida","family":"Bedja","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Danner","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Francois","family":"Jasmin","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Lisanti","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Friebe","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiki","family":"Takimoto","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Kass","sequence":"additional","affiliation":[{"name":"From the Section in Cardiology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA (E.J.T.); Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (E.J.T., Y.L.); the Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD (E.J.T., N.K., T.D., E.T.); the Department of Comparative Medicine and Comparative Pathology, Johns Hopkins University Medical Institutions, Baltimore, MD (D.B.); the..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.07.078"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.716373"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.800292"},{"key":"e_1_3_5_5_2","first-page":"H35","article-title":"Cardiac inducible nitric oxide synthase negatively modulates myocardial function in cultured rat myocytes","volume":"272","author":"Kinugawa KI","year":"1997","unstructured":"Kinugawa KI, Kohmoto O, Yao A, Serizawa T, Takahashi T . Cardiac inducible nitric oxide synthase negatively modulates myocardial function in cultured rat myocytes. Am J Physiol. 1997;272:H35\u2013H47.","journal-title":"Am J Physiol"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.1.91"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02190700"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.6.1223"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.74.5.970"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1175"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00526-X"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh0102.103222"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00059-5"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21968"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.65.5.1361"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.655266"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.822072"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.599241"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74313-0"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb775"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.083634"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105587200"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1078\/0065-1281-00602"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200104170-00023"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100828200"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00489.2004"},{"key":"e_1_3_5_27_2","first-page":"408","article-title":"Regulator of g protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of pde5 inhibition in mice","volume":"119","author":"Takimoto E","year":"2009","unstructured":"Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, Bedja D, Gabrielson KL, Blanton R, Siderovski DP, Mendelsohn ME, Kass DA . Regulator of g protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of pde5 inhibition in mice. J Clin Invest. 2009;119:408\u2013420.","journal-title":"J Clin Invest"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.182147"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.12.008"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28371"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00953.2010"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609778104"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi962047w"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2592"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1444"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27657"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(88)80539-8"},{"key":"e_1_3_5_38_2","first-page":"71","article-title":"Nitric oxide-independent activation of soluble guanylate cyclase by bay 60\u20132770 in experimental liver fibrosis","volume":"58","author":"Knorr A","year":"2008","unstructured":"Knorr A, Hirth-Dietrich C, Alonso-Alija C, Harter M, Hahn M, Keim Y, Wunder F, Stasch JP . Nitric oxide-independent activation of soluble guanylate cyclase by bay 60\u20132770 in experimental liver fibrosis. Arzneimittelforschung. 2008;58:71\u201380.","journal-title":"Arzneimittelforschung"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205511200"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.06.027"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.3109\/10799890903325585"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.226712"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.643536"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000200178.34179.93"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-010-0084-5"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01025.2002"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.03.224"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2009.215"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.12.032"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06484.x"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07908.x"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.737031"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.111.259242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:37:11Z","timestamp":1715557031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.111.259242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,20]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,1,20]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.259242"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.259242","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13625956.15025056","asserted-by":"object"}]},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,20]]},"assertion":[{"value":"2011-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}