Natriuretic peptides: degradation, circulating forms, dosages and new therapeutic approaches

Testing for natriuretic peptides (BNP, NT-proBNP or MR-proANP) is recommended by the European Society of Cardiology (ESC) since 2005 for the exclusion diagnosis of acute and chronic heart failure because of very high predictive values. Natriuretic peptides are produced by the heart in response to high transmural pressure and/or myocardial ischemia. These peptides circulate in blood of both healthy subjects and heart failure patients. Mass spectrometry methods allowed identifying a collection of circulating and degraded forms of BNP, NT-proBNP and proBNP. Glycosylated forms of NT-proBNP and proBNP have also been identified. Current immunoassays are lacking analytical specificity due to high cross-reactivities between circulating forms. Moreover, glycosylation has been found to interfere with the capacity of antibodies to bind correctly to analytes. These elements have been taken into account to propose strategies for the development of new standardized and improved immunoassays. More recently, the better understanding of the degradation pathways of natriuretic peptides allowed the raise of new therapeutic approaches for heart failure patients. All these elements are detailed in this review.