NPPB

NPPB Full Name

Natriuretic peptide B

NPPB Introduction

NPPB is the gene for natriuretic peptide B(BNP). BNP is a cardiac hormone. They are produced in the form of preproBNP, which is cleaved to form proBNP. proBNP was then cleaved to release BNP and inactive NT-proBNP fragments. BNP and NT-proBNP peptides appear in the circulatory system within minutes of elevated ventricular wall tension, excessive pressure load or myocardial injury. Therefore, NPPB is considered to be the main molecular mediator of the heart's adaptive response to hemodynamic stress.

Figure 1. Proposed intracellular transport and secretion of natriuretic peptides in cardiomyocytes.(Source: Goetze JP, et al.; 2020)

Mechanistically, BNP acts almost entirely through natriuretic peptide receptor A (NPR-A) to increase intracellular cGMP and cause vasodilation, natriuresis and diuresis, and inhibition of the renin–angiotensin–aldosterone system. This results in lower blood pressure, cardiac preload and afterload, and direct antifibrotic and antihypertrophic effects on the myocardium. This suggests that it may have a more physiologic role in systemic unloading independent of acute heart failure. Transcription of NPPB is tightly regulated by mechanical stretch, neurohormonal, and inflammatory mediators.

Clinically, NPPB dysregulation has been most strongly linked to cardiovascular disease. BNP and NT-proBNP are gold-standard, well-validated biomarkers for diagnosing and prognosing heart failure, acute coronary syndromes and structural heart disease. Elevated blood levels of BNP and NT-proBNP result from ventricular stretch. They have been demonstrated to have a strong correlation with disease severity and the risk of hospitalization or death. Altered BNP levels have also been linked to conditions outside of the realm of cardiology including renal dysfunction, pulmonary hypertension, sepsis and metabolic disorders. Polymorphisms in NPPB have been associated with blood pressure regulation and predisposition to hypertension. NPPB thus plays a role in the biology of cardiovascular risk factors and is a target for natriuretic peptide–based drug development.

• 1. Goetze JP, et al.; Cardiac natriuretic peptides. Nat Rev Cardiol. 2020, 17(11):698-717.