BNP Molecular Forms and Processing by the Cardiac Serine Protease Corin

The cardiac hormone, B-type natriuretic peptide (BNP), is one of human natriuretic peptides which possesses cardiorenal protective actions and is used as a therapeutic and a biomarker for heart failure (HF). Its prohormone, proBNP_1-108, is processed by the proNPs convertases, corin or furin, to inactive NT-proBNP_1-76 and active BNP_1-32. Paradoxically, circulating NT-proBNP and BNP are elevated in HF leading to the use of BNP as a sensitive and predictive marker of HF. This paradox may be explained by the "nonspecific" nature of conventional assays and/or a relative deficiency state of "active BNP" as characterized by an increase in inactive proBNP_1-108 and a decrease in active BNP_1-32. Therefore, understanding the regulation of proBNP_1-108 processing and the role of the convertase corin may be important in understanding the physiology of HF. Corin is expressed in heart and kidney and may play an important role in regulating blood pressure and remodeling of the heart. The processing of proBNP_1-108 by corin may be controlled by O-linked glycosylation of proBNP_1-108. A potential impairment of proBNP_1-108 processing in HF may be linked to dysregulation of the convertase corin, which may offer therapeutic opportunities to control proBNP_1-108 processing and its activation in HF.