{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:44:17Z","timestamp":1784335457016,"version":"3.55.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease. Corin converts proatrial natriuretic peptide into its active form after being activated by PCSK6 (proprotein convertase subtilisin\/kexin type 6) protease. It remains unknown whether the PCSK6\/corin\/atrial natriuretic peptide pathway plays a role in CKD\u2010induced cardiomyopathy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Serum corin, left ventricular mass index, and corin\u2013left ventricular mass index correlation were compared between outpatients with versus without CKD. Cardiac corin expression and activity as well as serum corin were compared between 5\/6 nephrectomy CKD animal models and sham controls. The effects of indoxyl sulfate, a uremic toxin, on cardiomyocytes were examined in vitro in H9c2 cells. A total of 543 patients were enrolled in this study. Serum corin levels were elevated in patients with CKD compared with levels in patients without CKD. Serum corin levels correlated negatively with left ventricular mass index in participants without CKD, but not in patients with CKD. Compared with sham controls, CKD mice had higher serum corin levels and increased cardiac expression of corin but reduced cardiac corin conversion activity. Indoxyl sulfate stimulated corin expression while suppressing serine protease activity in H9c2 cardiomyoblasts. Lower PCSK6 expression in CKD mouse hearts and indoxyl sulfate\u2013treated H9c2 cardiomyoblasts may explain, at least partly, the observed CKD\u2010associated reduction in corin activity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In CKD, cardiac and serum levels of corin are increased, yet corin activity is suppressed. The latter may be attributable to reduced PCSK6 expression. These findings suggest that corin dysfunction may play a significant role in the pathogenesis of CKD\u2010associated cardiomyopathy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.025208","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T11:17:21Z","timestamp":1657019841000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0077-7130","authenticated-orcid":false,"given":"Shang\u2010Feng","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine Cheng Hsin General Hospital Taipei Taiwan"},{"name":"Institute of Clinical Medicine National Yang Ming Chiao Tung University Taipei 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