Potential value of circulating corin levels in acute and chronic myocardial infarction

Potential value of circulating corin levels in acute and chronic myocardial infarction

Dong Wang, Guy L. Reed

Department of Medicine, University of Tennessee, College of Medicine, Memphis, TN 38163, USA

Correspondence to: Guy L. Reed, MD. Department of Medicine, University of Tennessee Health Science Center, Coleman, D334, 956 Court Ave, Memphis, TN 38163, USA. Email: glreed@uthsc.edu.

Provenance: This is a Guest Editorial commissioned by Section Editor Junhong Wang (Department of cardiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China).

Comment on: Zhou X, Chen J, Zhang Q, et al. Prognostic Value of Plasma Soluble Corin in Patients With Acute Myocardial Infarction. J Am Coll Cardiol 2016;67:2008-14.

Received: 12 May 2017; Accepted: 14 May 2017; Published: 09 June 2017.

doi: 10.21037/jlpm.2017.05.10

In the heart, corin is a membrane-anchored, serine protease that cleaves and activates pro-ANP and pro-BNP, thereby modulating salt-water balance, vasodilatation and cardiac function (1). Cardiac corin can also be released from cardiomyocyte membranes and enter the circulation as a soluble form, where it can readily be measured in the blood. Recent studies have shown a linkage between circulating or soluble corin and a broad spectrum of cardiovascular diseases, such as heart failure (HF) (2-4), stroke (5), diabetes (6) and hypertension (7,8). The diagnostic and prognostic significance of circulating corin in acute myocardial infarction (MI) have also been explored (4,9-12). The interesting recent report by Zhou et al. (11) of 1,382 of MI patients, including patients with ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), is the largest study to examine the clinical significance of circulating corin in acute MI. They found that plasma corin was a useful predictor of major adverse cardiac events (MACE), including all-cause mortality, HF hospitalization, or recurrent AMI and all-cause mortality. They also found that plasma corin has an important prognostic value, particularly, in STEMI patients (11). Other studies have also examined the value of circulating corin in predicting the prognosis of MI patients (Table 1) (9,10,12), but the findings are not consistent among these reports.

Table 1
Table 1 Summary of clinical studies related to circulating corin in acute MI
Full table

The pattern of change in circulating corin levels in patients with acute MI varies among these studies (Table 1). In the Zhou et al. study, controls were not included (11), however, in other studies, levels of circulating corin post MI were increased (12), decreased (9,10) or even unchanged (4), when compared to controls. There are potential reasons for the differences between these studies. First, the temporal pattern of corin levels following acute MI is unknown. Acute MI is likely to enhance the release of corin into the blood from necrotic and perhaps ischemic myocytes. Consistent with this notion, patients with acute STEMI undergoing acute reperfusion by percutaneous intervention were found to have increases in corin levels that were correlated with the size of their MI (12). Acute STEMI is typically associated with greater release of troponin and other cardiac biomarkers, reflecting greater ischemic injury, than non-STEMI (13). Second, ischemic cardiomyocytes and activated inflammatory cells secrete proteolytic enzymes, such as cathepsins, calcium-activated neutral proteases and matrix metalloproteinases (14-16), which may degrade corin in the blood. Unfortunately, in many of these studies, blood samples were not treated with protease inhibitors (9-11) and the time period of storage before testing is unclear. It is also unclear whether serum or plasma measurements affect corin levels. Third, there are significant variations among these studies in the timing of blood sampling in relation to the onset of ischemia. Table 1 shows that blood samples were collected from patients either on admission (11) or within 24 hours of admission (9,10). However the time of blood sampling in relation to the onset and duration of ischemic symptoms is unknown. Finally, there are differences among these studies in the patients studied; some studies only included STEMI patients (12), others represent a mixture of STEMI and NSTEMI (10,11), or acute coronary syndrome patients (9). Given the difference in severity of coronary artery occlusion and infarct size among these groups (17), we would predict significant differences in circulating corin levels, particularly if corin is released as result of cardiomyocyte injury or necrotic death, after MI.

How can we reconcile the observations of high soluble corin levels in acute MI, with the finding that low soluble corin levels are associated with poor longer term outcomes? In HF patients, circulating blood levels of corin are significantly lower than healthy controls (2,4,18). Experimental studies and analyses of explanted hearts show that corin transcript and protein levels are significantly reduced in HF (19-21). Indeed, there is a strong positive correlation between corin expression and left ventricular systolic function, with higher cardiac corin levels linked to higher ejection fractions (21). If corin blood levels reflect endogenous cardiac corin expression, it is logical that soluble corin levels will be suppressed in patients with underlying chronic ischemic cardiomyopathies. Nevertheless, during acute MI, there should be transient release of corin from ischemic and/or necrotic cardiomyocytes. The magnitude of rise in blood corin levels over time should reflect the amount of acute myocardial injury. However, in the chronic phase after acute MI, corin levels would be predicted to be lower, reflecting the severity of ischemic cardiomyopathy. In this way, corin may prove to have unique value as a biomarker, reflecting acute MI with rises in soluble levels and, in the chronic post-MI phase, as an indicator of the severity of ischemic cardiomyopathy. This study by Zhou et al., together with other recent studies, have suggested that soluble corin may have unique prognostic value, but clinical studies will be necessary to compare corin to other established biomarkers. In addition, experimental studies are needed to better understand the mechanisms and pathophysiologic significance of changes in soluble corin levels in acute and chronic ischemic heart disease.


Funding: This work was supported by American Heart Association grant (14SDG20510068 to D Wang) and NIH grants (HL092750, NS089707 to GL Reed).


Conflicts of Interest: Dr. Reed is a founder of Translational Sciences.


  1. Armaly Z, Assady S, Abassi Z. Corin: a new player in the regulation of salt-water balance and blood pressure. Curr Opin Nephrol Hypertens 2013;22:713-22. [Crossref] [PubMed]
  2. Ibebuogu UN, Gladysheva IP, Houng AK, et al. Decompensated heart failure is associated with reduced corin levels and decreased cleavage of pro-atrial natriuretic peptide. Circ Heart Fail 2011;4:114-20. [Crossref] [PubMed]
  3. Barnet CS, Liu X, Body SC, et al. Plasma corin decreases after coronary artery bypass graft surgery and is associated with postoperative heart failure: a pilot study. J Cardiothorac Vasc Anesth 2015;29:374-81. [Crossref] [PubMed]
  4. Dong N, Chen S, Yang J, et al. Plasma soluble corin in patients with heart failure. Circ Heart Fail 2010;3:207-11. [Crossref] [PubMed]
  5. Peng H, Zhu F, Shi J, et al. Serum Soluble Corin is Decreased in Stroke. Stroke 2015;46:1758-63. [Crossref] [PubMed]
  6. Fathy SA, Hamid FF, Zabut BM, et al. Diagnostic utility of BNP, corin and furin as biomarkers for cardiovascular complications in type 2 diabetes mellitus patients. Biomarkers 2015;20:460-9. [Crossref] [PubMed]
  7. Peng H, Zhang Q, Cai XQ, et al. Association Between High Serum Soluble Corin and Hypertension: A Cross-Sectional Study in a General Population of China. Am J Hypertens 2015;28:1141-9. [Crossref] [PubMed]
  8. Rame JE, Tam SW, McNamara D, 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. [Crossref] [PubMed]
  9. Peleg A, Ghanim D, Vered S, et al. 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. [Crossref] [PubMed]
  10. Zhang SM, Shen JX, Li H, et al. Association between serum corin levels and risk of acute myocardial infarction. Clin Chim Acta 2016;452:134-7. [Crossref] [PubMed]
  11. Zhou X, Chen J, Zhang Q, et al. Prognostic Value of Plasma Soluble Corin in Patients With Acute Myocardial Infarction. J Am Coll Cardiol 2016;67:2008-14. [Crossref] [PubMed]
  12. Feistritzer HJ, Klug G, Reinstadler SJ, et al. Circulating corin concentrations are related to infarct size in patients after ST-segment elevation myocardial infarction. Int J Cardiol 2015;192:22-3. [Crossref] [PubMed]
  13. Di Stefano R, Di Bello V, Barsotti MC, et al. Inflammatory markers and cardiac function in acute coronary syndrome: difference in ST-segment elevation myocardial infarction (STEMI) and in non-STEMI models. Biomed Pharmacother 2009;63:773-80. [Crossref] [PubMed]
  14. Bolli R, Cannon RO, Speir E, et al. Role of cellular proteinases in acute myocardial infarction. I. Proteolysis in nonischemic and ischemic rat myocardium and the effects of antipain, leupeptin, pepstatin and chymostatin administered in vivo. J Am Coll Cardiol 1983;2:671-80. [Crossref] [PubMed]
  15. Jordan JE, Zhao ZQ, Vinten-Johansen J. The role of neutrophils in myocardial ischemia-reperfusion injury. Cardiovasc Res 1999;43:860-78. [Crossref] [PubMed]
  16. Phatharajaree W, Phrommintikul A, Chattipakorn N. Matrix metalloproteinases and myocardial infarction. Can J Cardiol 2007;23:727-33. [Crossref] [PubMed]
  17. de Winter RJ, Tijssen JGP. Non-ST-Segment Elevation Myocardial Infarction Revascularization for Everyone? JACC-Cardiovascular Interventions 2012;5:903-5. [Crossref] [PubMed]
  18. Zhou X, Chen JC, Liu Y, et al. Plasma Corin as a Predictor of Cardiovascular Events in Patients With Chronic Heart Failure. JACC Heart Fail 2016;4:664-9. [Crossref] [PubMed]
  19. Ichiki T, Boerrigter G, Huntley BK, et al. Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis. Am J Physiol Regul Integr Comp Physiol 2013;304:R102-9. [Crossref] [PubMed]
  20. Lee R, Xu B, Rame JE, et al. Regulated inositol-requiring protein 1-dependent decay as a mechanism of corin RNA and protein deficiency in advanced human systolic heart failure. J Am Heart Assoc 2014;3:e001104. [Crossref] [PubMed]
  21. Tripathi R, Wang D, Sullivan R, et al. Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development. Hypertension 2016;67:362-7. [PubMed]
doi: 10.21037/jlpm.2017.05.10
Cite this article as: Wang D, Reed GL. Potential value of circulating corin levels in acute and chronic myocardial infarction. J Lab Precis Med 2017;2:26.