LAUSR

T he discovery of natriuretic peptides in the 1980s revolutionized the perspective of biochemical biomarkers in the diagnosis, monitoring, and treatment of cardiac diseases. Atrial natriuretic peptide (ANP) was first identified, followed by B-type natriuretic peptide (BNP), whose roles in cardiovascular physiology and pathophysiology were promptly discovered. BNP is synthesized in the heart, both in atria and in the ventricle’s myocytes and fibroblasts, from the prohormone B-type natriuretic peptide (proBNP), which is split upon secretion into the biologically active BNP and the biologically inactive N-terminal pro–B-type natriuretic peptide (NT-proBNP) through the action of the proteolytic enzymes furin and corin (1). Myocardial stretch signal is the key stimulant for BNP synthesis through activation of the proBNP gene, but catecholamines, angiotensin II, endothelin, hypoxia, inflammation, and fibrosis are also factors known to stimulate BNP release, as observed in both animal and human studies. Upon release, BNP binds to the specific guanylyl cyclase A membrane receptor, activating the second messenger 3’,5’-cyclic guanosine monophosphate. Although NT-proBNP is biologically inactive, BNP induces pleiotropic effects, namely increased diuresis and vasodilation, reduced activity of the renin-angiotensin-aldosterone axis, suppression of cardiac hypertrophy, myocardial fibrosis, and apoptosis, as well as a number of metabolic protective effects (1). In terms of fibrosis, BNP regulates a number of key elements, such as