Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity
Background 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/cori...
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.025208 |
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| author | Shang‐Feng Yang Szu‐Yuan Li Feng‐Yen Lin Tsung‐Han Hsieh Po‐Hsun Huang Shing‐Jong Lin |
| author_facet | Shang‐Feng Yang Szu‐Yuan Li Feng‐Yen Lin Tsung‐Han Hsieh Po‐Hsun Huang Shing‐Jong Lin |
| author_sort | Shang‐Feng Yang |
| collection | DOAJ |
| description | Background 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‐induced cardiomyopathy. Methods and Results Serum corin, left ventricular mass index, and corin–left 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–treated H9c2 cardiomyoblasts may explain, at least partly, the observed CKD‐associated reduction in corin activity. Conclusions 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‐associated cardiomyopathy. |
| first_indexed | 2024-04-10T18:24:25Z |
| format | Article |
| id | doaj.art-4ccbebf5244641ce93a75ad872e419cb |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T18:24:25Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-4ccbebf5244641ce93a75ad872e419cb2023-02-02T06:20:21ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-07-01111410.1161/JAHA.121.025208Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion ActivityShang‐Feng Yang0Szu‐Yuan Li1Feng‐Yen Lin2Tsung‐Han Hsieh3Po‐Hsun Huang4Shing‐Jong Lin5Division of Nephrology, Department of Medicine Cheng Hsin General Hospital Taipei TaiwanDivision of Nephrology, Department of Medicine Taipei Veterans General Hospital Taipei TaiwanDivision of Cardiology and Cardiovascular Research Center, Department of Internal Medicine Taipei Medical University Hospital Taipei TaiwanJoint Biobank, Office of Human Research Taipei Medical University Taipei TaiwanInstitute of Clinical Medicine National Yang Ming Chiao Tung University Taipei TaiwanInstitute of Clinical Medicine National Yang Ming Chiao Tung University Taipei TaiwanBackground 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‐induced cardiomyopathy. Methods and Results Serum corin, left ventricular mass index, and corin–left 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–treated H9c2 cardiomyoblasts may explain, at least partly, the observed CKD‐associated reduction in corin activity. Conclusions 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‐associated cardiomyopathy.https://www.ahajournals.org/doi/10.1161/JAHA.121.025208atrial natriuretic peptidechronic kidney diseasecorinPCSK6uremic cardiomyopathy |
| spellingShingle | Shang‐Feng Yang Szu‐Yuan Li Feng‐Yen Lin Tsung‐Han Hsieh Po‐Hsun Huang Shing‐Jong Lin Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial natriuretic peptide chronic kidney disease corin PCSK6 uremic cardiomyopathy |
| title | Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity |
| title_full | Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity |
| title_fullStr | Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity |
| title_full_unstemmed | Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity |
| title_short | Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity |
| title_sort | chronic kidney disease is associated with increased cardiac corin expression but decreased proatrial natriuretic peptide conversion activity |
| topic | atrial natriuretic peptide chronic kidney disease corin PCSK6 uremic cardiomyopathy |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.025208 |
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