Corin Is Present in the Normal Human Heart, Kidney, and Blood, with Pro–B-Type Natriuretic Peptide Processing in the Circulation

Abstract

BACKGROUND B-type natriuretic peptide (BNP), which is activated in heart failure (HF), is processed to an active form by corin. The corin gene is expressed in the human heart and kidney, but corin protein expression in the heart, kidney, and circulation, along with whether proBNP is processed by circulating corin, remains unknown. METHODS We examined corin protein expression by immunostaining and Western blot in human heart and kidney, and we assessed the circulating corin concentration by ELISA. We examined histidine-tagged (His-tag) proBNP1–108 processing in serum and plasma by immunoprecipitation and Western blot and sequenced the processed form. RESULTS Normal human heart and kidney displayed the presence of corin, especially in cells around the vasculature. Both corin and proBNP1–108 were present in the plasma of healthy human subjects, with circulating corin significantly higher in men than women (P < 0.0001) and a positive correlation of corin to age (P = 0.0497, r = 0.27). In fresh normal plasma and serum, His-tag proBNP1–108 was processed to a lower molecular weight form confirmed to be BNP. Processed BNP was higher in men than women (P = 0.041) and was positively correlated to plasma corin concentrations (P = 0.041, r = 0.65). CONCLUSIONS Our results support the concept that proBNP1–108 may be processed outside of the heart in the circulation where the proprotein convertase is present. Moreover, sex may impact this process, since corin concentrations are higher in men. These findings may have important physiologic and pathophysiologic implications for the proBNP/corin system in the human.

Corin Mutation R539C from Hypertensive Patients Impairs Zymogen Activation and Generates an Inactive Alternative Ectodomain Fragment

“…Cleaved corin fragments may enter the circulation. Corin antigen and activity have been detected in human blood (43)(44)(45)(46). Studies indicate that the levels of plasma soluble corin and activity are significantly lower in patients with hypertension and heart failure (43,47,48), suggesting that the reduced corin activity may contribute to hypertensive disease.…”

Processed B-Type Natriuretic Peptide Is a Biomarker of Postinterventional Restenosis in Ischemic Heart Disease

“…ProBNP(1-108) is cleaved to a biologically inactive amino-terminal NT-proBNP(1-76) and active BNP(1-32) (13 ). A cardiac transmembrane serine protease, corin, and a ubiquitous serine protease, furin, are currently proposed as possible convertases (16,28,29 ). Recently, other processed forms of BNP, including BNP(3-32), BNP(4 -32), and BNP(5-32), have been detected in plasma from heart failure patients in the presence of protease inhibitors benzamidine (as a trypsin, plasmin, thrombin inhibitor) and 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (as an inhibitor for serine protease such as DPP-IV) to minimize the effect of protease degradation (15 ).…”

Innovative Strategy in Therapy of Cardiac Insufficiency

“…Триггером для синтеза CНУП клетками эндотелия является выброс цитокинов и эндотелий-зависимых аго-нистов (ацетилхолин) [17][18][19][20]. Для CНУП также характер-ны выраженные кардиовазальные эффекты: снижение сердечного выброса, уменьшение давления наполнения левого желудочка, вазодилатация.…”