{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:59:36Z","timestamp":1791190776011,"version":"4.1.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,3,2]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      The source of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      to activate pathological cardiac hypertrophy is not clearly defined. Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx through the L-type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels (LTCCs) determines \u201ccontractile\u201d Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , which is not thought to be the source of \u201chypertrophic\u201d Ca\n                      <jats:sup>2+<\/jats:sup>\n                      . However, some LTCCs are housed in caveolin-3 (Cav-3)\u2013enriched signaling microdomains and are not directly involved in contraction. The function of these LTCCs is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      To test the idea that LTCCs in Cav-3\u2013containing signaling domains are a source of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      to activate the calcineurin\u2013nuclear factor of activated T-cell signaling cascade that promotes pathological hypertrophy.\n                    <\/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                      We developed reagents that targeted Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channel-blocking Rem proteins to Cav-3\u2013containing membranes, which house a small fraction of cardiac LTCCs. Blocking LTCCs within this Cav-3 membrane domain eliminated a small fraction of the LTCC current and almost all of the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx-induced NFAT nuclear translocation, but it did not reduce myocyte contractility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      We provide proof of concept that Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx through LTCCs within caveolae signaling domains can activate \u201chypertrophic\u201d signaling, and this Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx can be selectively blocked without reducing cardiac contractility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.111.264028","type":"journal-article","created":{"date-parts":[[2012,2,3]],"date-time":"2012-02-03T20:30:31Z","timestamp":1328301031000},"page":"669-674","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":116,"title":["A Caveolae-Targeted L-Type Ca\n                    <sup>2+<\/sup>\n                    Channel Antagonist Inhibits Hypertrophic Signaling Without Reducing Cardiac Contractility"],"prefix":"10.1161","volume":"110","author":[{"given":"Catherine A.","family":"Makarewich","sequence":"first","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N.","family":"Correll","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remus M.","family":"Berretta","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Rizzo","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Houser","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (C.A.M., H.G., H.Z., R.M.B., S.R.H.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics (R.N.C., J.D.M.), University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children's Hospital Medical Center, Cincinnati, OH; Cardiovascular Research Center and Department of Anatomy and Cell Biology (B.Y., V.R.), Temple University School of Medicine, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100455"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.121"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8551"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27374"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31060"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.11.012"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39724"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000189270.72915.d1"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.225888"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503465103"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.224717"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706176200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.10.6525"},{"key":"e_1_3_4_16_2","first-page":"H891","article-title":"Isolation and morphology of calcium-tolerant feline ventricular myocytes","volume":"245","author":"Silver LH","year":"1983","unstructured":"Silver LH, Hemwall EL, Marino TA, Houser SR. Isolation and morphology of calcium-tolerant feline ventricular myocytes. Am J Physiol. 1983;245:H891\u2013H896.","journal-title":"Am J Physiol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01044.2006"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.194035"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.216127"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.064212"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.111.264028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:30:54Z","timestamp":1715556654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.111.264028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,2]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,3,2]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.264028"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.264028","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.14267047.15779419","asserted-by":"object"}]},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,2]]},"assertion":[{"value":"2011-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}