Corin in Natriuretic Peptide Processing and Hypertension
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Corin is a serine protease originally isolated from the heart. Functional studies show that corin is the long-sought enzyme responsible for activating cardiac natriuretic peptides. In mice, lack of corin prevents natriuretic peptide processing, causing salt-sensitive hypertension. In humans, corin variants and mutations that reduce corin activity have been identified in patients with hypertension and heart failure. Decreased plasma levels of corin antigen and activity have been reported in patients with heart failure and coronary artery disease. Low levels of urinary corin also have been found in patients with chronic kidney disease. Most recent studies show that corin also acts in the uterus to promote spiral artery remodeling and prevent pregnancy-induced hypertension. Here, we review the role of corin in natriuretic peptide processing and cardiovascular diseases such as hypertension, heart disease, pre-eclampsia, and chronic kidney disease.
KeywordsAfrican American ANP BNP Cardiac hypertrophy Chronic kidney disease CNP Corin ENaC Gene mutation Gene variant Heart failure Hypertension Natriuretic peptides Pre-eclampsia Salt-sensitive hypertension Spiral artery remodeling Trophoblast invasion
We would like to thank our co-workers, past and present, who contributed to corin studies. This work was supported in part by NIH grants R01 HL089298 and HD064634, and grants from the National Natural Science Foundation of China (31070716, 81170247 and 31161130356) and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
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Conflict of Interest
Yiqing Zhou and Qingyu Wu declare that they have no conflicts of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 5.•Barbato E, Bartunek J, Mangiacapra F, Sciarretta S, Stanzione R, Delrue L, et al. Influence of rs5065 atrial natriuretic peptide gene variant on coronary artery disease. J Am Coll Cardiol. 2012;59:1763–70. References 5 and 6 describe the association of a minor ANP gene allele, encoding an ANP variant with two extra C-terminal Arg residues, with an increased risk of cardiovascular disease in European and American populations.PubMedGoogle Scholar
- 6.•Cannone V, Huntley BK, Olson TM, Heublein DM, Scott CG, Bailey KR, et al. Atrial natriuretic peptide genetic variant rs5065 and risk for cardiovascular disease in the general community: a 9-year follow-up study. Hypertension. 2013;62:860–5. References 5 and 6 describe the association of a minor ANP gene allele, encoding an ANP variant with two extra C-terminal Arg residues, with an increased risk of cardiovascular disease in European and American populations.PubMedPubMedCentralGoogle Scholar
- 9.Nakayama T, Soma M, Takahashi Y, Rehemudula D, Kanmatsuse K, Furuya K. Functional deletion mutation of the 5'-flanking region of type A human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese. Circ Res. 2000;86:841–5.PubMedGoogle Scholar
- 10.•Sciarretta S, Marchitti S, Bianchi F, Moyes A, Barbato E, Di Castro S, et al. C2238 atrial natriuretic peptide molecular variant is associated with endothelial damage and dysfunction through natriuretic peptide receptor C signaling. Circ Res. 2013;112:1355–64. This study shows that the ANP variant with two C-terminal Arg residues impaired endothelial cell survival and function through abnormal activation of natriuretic peptide receptor-C.PubMedGoogle Scholar
- 11.•Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessi-Fulgheri P, Zhang C, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122:1022–36. This study shows that ANP and BNP enhance the thermogenic program in mouse and human brown adipose tissues, revealing a novel mechanism of the cardiac natriuretic peptides in regulating energy metabolism.PubMedPubMedCentralGoogle Scholar
- 12.•Engeli S, Birkenfeld AL, Badin PM, Bourlier V, Louche K, Viguerie N, et al. Natriuretic peptides enhance the oxidative capacity of human skeletal muscle. J Clin Invest. 2012;122:4675–9. This study shows that ANP and BNP promote oxidative metabolism in human skeletal muscles, which may contribute to improved skeletal muscle fat oxidation through exercise.PubMedPubMedCentralGoogle Scholar
- 53.•Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, et al. Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks. Hypertension. 2012;60:1352–8. This study shows that the corin variant T555I/Q568P was defective in vivo and contibuted to salt-sensitive hypertension and cardiac hypertrophy, which resembled the phenotype in the African Americans carrying the corin variant allele.PubMedPubMedCentralGoogle Scholar
- 59.Rame JE, Tam SW, McNamara D, Worcel M, Sabolinski ML, Wu AH, et al. Dysfunctional corin I555(P568) allele is associated with impaired brain natriuretic peptide processing and adverse outcomes in blacks with systolic heart failure: results from the Genetic Risk Assessment in Heart Failure substudy. Circ Heart Fail. 2009;2:541–8.PubMedPubMedCentralGoogle Scholar
- 79.Ibebuogu UN, Gladysheva IP, Houng AK, Reed GL. Decompensated heart failure is associated with reduced corin levels and decreased cleavage of pro-atrial natriuretic peptide. Circ Heart Fail. 2011;2011:114–20.Google Scholar
- 80.•Peleg A, Ghanim D, Vered S, Hasin Y. Serum corin is reduced and predicts adverse outcome in non-ST-elevation acute coronary syndrome. Eur Heart J Acute Cardiovasc Care. 2013;2:159–65. This study shows that reduced serum soluble corin levels were associated with major adverse cardiovascular events in patients with acute coronary syndrome.PubMedPubMedCentralGoogle Scholar
- 82.•Gladysheva IP, Wang D, McNamee RA, Houng AK, Mohamad AA, Fan TM, et al. Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy. Hypertension. 2013;61:327–32. This study shows in a genetic mouse model of heart failure that overexpression of corin improved cardiac function, reduced pulmonary edema and increased survival, supporting a therapeutic strategy to enhance corin activity to treat heart failure patients.PubMedGoogle Scholar
- 86.••Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, et al. Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature. 2012;484:246–50. This study identifies a novel corin function in the uterus to promote trophoblast invasion and uterine spiral artery remodeling, which are important for preventing pregnancy-induced hypertension. This study also reports corin gene mutations that reduced corin activity in patients with pre-eclampsia.PubMedPubMedCentralGoogle Scholar
- 96.Fang C, Shen L, Dong L, Liu M, Shi S, Dong N, et al. Reduced urinary corin levels in patients with chronic kidney disease. Clin Sci (Lond). 2013;124:709–17.Google Scholar
- 100.••Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, et al. GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med. 2013;19:567–75. This study identifies a novel gut–heart link, in which gut-derived glucagon-like peptide-1 acts on glucagon-like peptide-1 receptor in the heart to promote ANP secretion, thereby regulating blood pressure and energy metabolism.PubMedGoogle Scholar