{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:52:33Z","timestamp":1790052753545,"version":"4.0.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,7,13]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Left ventricular diastolic dysfunction is a major cause of cardiac allograft failure. Multimeric L-type calcium channels (\u03b1\n            <jats:sub>1<\/jats:sub>\n            -, \u03b1\n            <jats:sub>2<\/jats:sub>\n            \/\u03b4-, and \u03b2-subunits) are essential for excitation\/contraction coupling in the heart. Their gene expression was studied in allografts that developed diastolic heart failure.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014mRNA levels of calcium channel subunits were measured by competitive reverse transcriptase\u2013polymerase chain reaction in microbiopsy samples from the interventricular septum. Size and tissue variabilities between biopsy samples were assessed by determination of cardiac calsequestrin mRNA levels. In the cardiac allografts studied, mRNA levels in microbiopsy samples were considered to represent left ventricular gene expression, because septal and left ventricular gene expression in Northern blots was equivalent, and left ventricles contracted homogeneously. Biopsy samples (n=72) were taken from allografts with normal left ventricular end-diastolic pressure (LVEDP; 8 to 13 mm Hg; n=30), moderately elevated LVEDP (14 to 18 mm Hg; n=26), and elevated LVEDP (19 to 28 mm Hg; n=16). Increased LVEDP was related to slowed diastolic relaxation determined by the time constant \u03c4 (\n            <jats:italic>r<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            =0.86), whereas systolic performance (dP\/dt; ejection fraction) was preserved. With increasing LVEDP, mRNA levels of the pore-forming \u03b1\n            <jats:sub>1c<\/jats:sub>\n            -subunit (n=15) and of the regulatory \u03b1\n            <jats:sub>2<\/jats:sub>\n            \/\u03b4-subunit (n=17) remained unchanged but decreased exponentially (\n            <jats:italic>r<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            =\u22120.83) for the regulatory \u03b2-subunit (n=40). Compared with cardiac allografts with normal LVEDP (n=15), \u03b2-subunit mRNA level was reduced by 75% at elevated LVEDP (n=9;\n            <jats:italic>P<\/jats:italic>\n            =0.012). In an explanted, diastolically failing cardiac allograft, \u03b2-subunit expression was reduced correspondingly by 72% and 76% on the mRNA level in septal and left ventricular myocardium and by 80% on the protein level.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The downregulated expression of the calcium channel \u03b2-subunit might contribute to altered calcium handling in diastolically failing cardiac allografts.\n          <\/jats:p>","DOI":"10.1161\/01.cir.100.2.155","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"155-163","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Subunit Expression of the Cardiac L-Type Calcium Channel Is Differentially Regulated in Diastolic Heart Failure of the Cardiac Allograft"],"prefix":"10.1161","volume":"100","author":[{"given":"Roger","family":"Hullin","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine I (R.H., F.A., J.H., P.B.), University Hospital Gro\u00dfhadern, Munich, Germany, and Department of Pharmacology (A.L.), Technical University, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Asmus","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (R.H., F.A., J.H., P.B.), University Hospital Gro\u00dfhadern, Munich, Germany, and Department of Pharmacology (A.L.), Technical University, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ludwig","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (R.H., F.A., J.H., P.B.), University Hospital Gro\u00dfhadern, Munich, Germany, and Department of Pharmacology (A.L.), Technical University, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Hersel","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (R.H., F.A., J.H., P.B.), University Hospital Gro\u00dfhadern, Munich, Germany, and Department of Pharmacology (A.L.), Technical University, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Boekstegers","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (R.H., F.A., J.H., P.B.), University Hospital Gro\u00dfhadern, Munich, Germany, and Department of Pharmacology (A.L.), Technical University, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.13.6228"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006863520835"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.72.6.7916667"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05126.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80135-H"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1716787"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80358-X"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.395"},{"key":"e_1_3_2_9_2","unstructured":"Hullin R Hersel J Jung S Asmus F Boekstegers P. 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Methods Mol Biol. 1994;32:5\u20138.","journal-title":"Methods Mol Biol"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00925961"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.4.6.371"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.4960030104"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.6.2069"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.9.2353"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00788733"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3207"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)50042-9"},{"key":"e_1_3_2_38_2","unstructured":"Qin N Olcese R Zhou J Cabello OA Birnbaumer L Stefani E. Identification of a second region of the \u03b2-subunit in regulation of calcium channel inactivation. Am J Physiol. 1996;271(Cell Physiol 40):C1539\u2013C1545.Gene expression of L-type calcium channel subunits was studied in cardiac allografts (n=72) with normal and diastolic heart failure. mRNA expression of the pore-forming \u03b11-subunit and of the regulatory \u03b12\/\u03b4- and \u03b2-subunits was determined quantitatively by competitive reverse transcription\u2013polymerase chain reaction. \u03b2-Subunit mRNA expression (n=40) decreased with impairment of diastolic function (r2=\u22120.83) resulting in a marked reduction (75%) in severe diastolic failure. In an explanted diastolically failing cardiac allograft \u03b2-subunit mRNA levels were decreased correspondingly in septal\/left ventricular myocardium (72%\/76%) and by 80% on the protein level. \u03b11- and \u03b12\/\u03b4-subunit mRNA expression remained unchanged."}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.100.2.155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T12:58:22Z","timestamp":1715518702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.100.2.155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7,13]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1999,7,13]]}},"alternative-id":["10.1161\/01.CIR.100.2.155"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.100.2.155","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,7,13]]},"assertion":[{"value":"1998-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-04-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-07-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}