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This Article Full Text Full Text (PDF) All Versions of this Article: 287/4/H1516    most recent 00947.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Langenickel, T. H. Articles by Bader, M. Search for Related Content PubMed PubMed Citation Articles by Langenickel, T. H. Articles by Bader, M.

Rat corin gene: molecular cloning and reduced expression in experimental heart failure

¹Max-Delbrueck-Center for Molecular Medicine, Berlin 13092; and ²Franz-Volhard-Klinik, Charité Campus Berlin-Buch, Humboldt-University, Berlin 13125, Germany

Submitted 6 October 2003 ; accepted in final form 12 May 2004

Stored cardiac pro-atrial natriuretic peptide (pro-ANP) is converted to ANP and released upon stretch from the atria into the circulation. Corin is a serin protease with pro-ANP-converting properties and may be the rate-limiting enzyme in ANP release. This study was aimed to clone and sequence corin in the rat and to analyze corin mRNA expression in heart failure when ANP release upon stretch is blunted. Full-length cDNA of rat corin was obtained from atrial RNA by RT-PCR and sequenced. Tissue distribution as well as regulation of corin mRNA expression in the atria were determined by RT-PCR and RNase protection assay. Heart failure was induced by an infrarenal aortocaval shunt. Stretch was applied to the left atrium in a working heart modus, and ANP was measured in the perfusates. The sequence of rat corin cDNA was found to be 93.6% homologous to mouse corin cDNA. Corin mRNA was expressed almost exclusively in the heart with highest concentrations in both atria. The aortocaval shunt led to cardiac hypertrophy and heart failure. Stretch-induced ANP release was blunted in shunt animals (control 1,195 ± 197 fmol·min^–1·g^–1; shunt: 639 ± 99 fmol·min^–1·g^–1, P < 0.05). Corin mRNA expression was decreased in both atria in shunt animals [right atrium: control 0.638 ± 0.004 arbitrary units (AU), shunt 0.566 ± 0.014 AU, P < 0.001; left atrium: control 0.564 ± 0.009 AU, shunt 0.464 ± 0.009 AU, P < 0.001]. Downregulation of atrial corin mRNA expression may be a novel mechanism for the blunted ANP release in heart failure.

gene expression; atrial natiuretic factor

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