A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction

B-type natriuretic peptide (BNP) is a cardiac-derived peptide hormone that consists of a 17-AA ring structure created by a disulfide bond joining 2 cysteine residues with distinct N and C terminal extensions. BNP binds to its particulate guanylyl cyclase receptor (GC) -A to activate the second messenger, cyclic GMP. Studies have established widespread pleuripotent actions that result in natriuresis, vasorelaxation, inhibition of renin and aldosterone, enhanced myocardial relaxation, inhibition of fibrosis and hypertrophy, promotion of cell survival, angiogenesis, and inhibition of inflammation.1,2 The clinical therapeutic potential of BNP continues to emerge, with studies demonstrating that it protects against diabetic nephropathy when genetically overexpressed by gene transfer,3 lowers blood pressure when delivered orally in experimental hypertension,4 and is cardioprotective when administered to humans undergoing cardiopulmonary bypass surgery.5Article see p 255 Most recently, studies have focused on the processing of BNP from its production to its degradation. BNP is produced as a preprohormone that subsequently is processed into a prohormone by cleavage of an N-terminal signal peptide (see the Figure). Human preproBNP is a 134-AA peptide that is cleaved to the 108-AA proBNP.6 Processing of proBNP to mature BNP is mediated by corin, and a role for furin has also been implicated.7,8 Human BNP, a 32-AA peptide, is released from the myocardium in response to various physiological and pathophysiological stimuli such as myocardial wall stretch, with evidence that myocardial ischemia releases BNP.9 Once released, BNP is cleared by the natriuretic peptide clearance receptor, which is widely expressed.1 Importantly, BNP is degraded by neutral endopeptidase 24.1110 but also by dipeptidyl peptidase IV,11 the latter resulting in a novel BNP3-32, which possesses altered cardiorenal actions and may uniquely function at the tissue level as a locally acting BNP. Figure. PreproBNP amino acid sequences …