Cardiac natriuretic peptides: from basic discovery to clinical practice

Discoveries of the cardiac natriuretic peptides ANP, BNP, and CNP along with studies of their function and regulation in health and disease, have led to breakthroughs in the understanding and clinical management of heart failure. Analysis of the ANP and BNP promoters and patterns of expression uncovered a set of key regulators and pathways that converge onto these sensitive markers of early myocyte differentiation and cardiac stress. Among the most studied are the transcription factors GATA4, TBX5, and NKX2-5, which are central to cardiac development and mutations of which are associated with congenital heart disease. In clinical practice, plasma natriuretic peptides levels have been used as quantitative biomarkers of heart failure and proved to be highly effective for the diagnosis of heart failure, for risk-stratification of patients and guided therapy, as well as for screening for subclinical cardiac stress. Emerging studies are revealing the cardioprotective attributes of these peptides and may offer new therapeutic venues for myocardial infarction and heart failure. Clinical trials have documented the benefits and risks of the use of synthetic ANP (Anaritide) and BNP (Nesiritide) for treating heart failure, renal failure, and hypertension. This review summarizes the function and regulation of cardiac natriuretic peptides and the translation of the basic biochemical discoveries into clinical practice both at the diagnostic and therapeutic level.