NT-ProBNP: the mechanism behind the marker.
Brain natriuretic peptide (BNP) was isolated originally from porcine brain extracts but was soon defined as a cardiac natriuretic hormone. Together with the highly homologous atrial natriuretic peptide, it forms a dual natriuretic peptide system of the heart. The main stimulus for proBNP synthesis and secretion from cardiac myocytes is myocyte stretch. On secretion, the propeptide is split into the biologically active BNP and the remaining part of the prohormone N-terminal proBNP (NT-proBNP). In heart failure increased wall stretch, neurohormonal activation and hypoxia stimulate BNP secretion. The recently demonstrated production of BNP by stimulated cardiac fibroblasts is of uncertain pathophysiologic importance. In contrast to atrial natriuretic peptide, BNP is a constitutively secreted hormone with relatively little intracellular storage of mature peptide. In the normal state, the atrium is the main cardiac production site, but as heart failure develops, there is a profound activation of ventricular NT-proBNP synthesis. BNP acts on distant tissues and causes diuresis, vasodilatation, and decreased renin and aldosterone secretion. Known mechanisms of BNP clearance from plasma include binding to the natriuretic peptide clearance receptor type-C and proteolysis by peptidase NEP 24.11. NT-proBNP has a longer half-life and thus higher plasma concentration than BNP. It probably is cleared from plasma by renal excretion and possibly other unknown pathways.
Hall
Christian
C
Department of Medicine, Akershus University Hospital, Lørenskog, Norway.
D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis* / Q000502:physiology*; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000502:physiology
D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain