# NPPB

## Overview
The NPPB gene encodes the precursor to B-type natriuretic peptide (BNP), a hormone that plays a pivotal role in cardiovascular physiology. BNP is primarily synthesized in the cardiac ventricles and is involved in the regulation of blood pressure and fluid balance through its vasodilatory, natriuretic, and diuretic effects. As a member of the natriuretic peptide family, BNP exerts its biological functions by interacting with specific receptors, notably the natriuretic peptide receptor type A (NPR-A), leading to increased levels of cyclic guanosine monophosphate (cGMP) and subsequent activation of downstream signaling pathways (Pandey2021Molecular; Giovou2024The). Additionally, BNP has antifibrotic properties, contributing to the inhibition of cardiac remodeling and fibrosis, which are critical for maintaining cardiac function and structure (Giovou2024The). Due to its longer half-life compared to other natriuretic peptides, BNP serves as a valuable biomarker for heart failure diagnosis and management (Giovou2024The).

## Function
The NPPB gene encodes the precursor to B-type natriuretic peptide (BNP), a hormone primarily produced in the ventricles of the heart. BNP plays a critical role in cardiovascular homeostasis by promoting vasodilation, natriuresis, and diuresis, which collectively help to reduce blood pressure and blood volume (Giovou2024The). In healthy human cells, BNP exerts its effects through the natriuretic peptide receptor type A (NPR-A), which increases intracellular cyclic guanosine monophosphate (cGMP) levels. This activation leads to downstream signaling cascades involving cGMP-dependent protein kinases, cGMP-gated ion channels, and cGMP-regulated cyclic nucleotide phosphodiesterases, contributing to the regulation of blood pressure and fluid balance (Giovou2024The).

BNP also plays a role in inhibiting cardiac remodeling and fibrosis by suppressing collagen synthesis and upregulating matrix metalloproteinases (MMPs), which are essential for extracellular matrix degradation. This action helps to reduce fibrosis and maintain cardiac function (Giovou2024The). The longer half-life of BNP in plasma compared to atrial natriuretic peptide (ANP) makes it a more effective biomarker for heart failure (Giovou2024The). Overall, BNP is crucial for maintaining cardiovascular function and homeostasis in healthy human cells.

## Clinical Significance
Mutations or alterations in the expression of the NPPB gene, which encodes B-type natriuretic peptide (BNP), are associated with several cardiovascular diseases. BNP plays a crucial role in regulating blood pressure and cardiac function. Deficiency in BNP, as observed in Nppb knockout models, leads to progressive hypertension, cardiac remodeling, and renal damage, ultimately reducing survival. These models serve as a representation of human hypertension, highlighting BNP's role in preventing cardiac fibrosis and hypertrophy (Holditch2015BType).

Increased expression of fibrosis-associated genes and hypertrophic signaling pathways in the absence of BNP suggests that BNP insufficiency preactivates these pathways, contributing to cardiac fibrosis and hypertrophic cardiomyopathy (Tamura2000Cardiac; Holditch2015BType). BNP's antifibrotic properties are crucial in maintaining cardiac structure, and its absence can lead to multifocal fibrotic lesions and ventricular remodeling (Tamura2000Cardiac).

Epigenetic regulation of NPPB expression is also significant, as dysregulation can lead to cardiac fibrosis and other pathological conditions. Understanding these regulatory mechanisms is essential for identifying therapeutic targets for cardiovascular diseases (Rubattu2020Epigenetic).

## Interactions
NPPB, or natriuretic peptide B, primarily interacts with natriuretic peptide receptors, particularly NPRA (natriuretic peptide receptor A), to mediate its physiological effects. The binding of NPPB to NPRA induces a conformational change in the receptor, activating its guanylyl cyclase catalytic region, which leads to the production of the second messenger cGMP. This signaling pathway is crucial for regulating cardiovascular functions such as vasorelaxation, natriuresis, and diuresis (Pandey2021Molecular).

NPPB also interacts with NPRC (natriuretic peptide receptor C), which acts as a clearance receptor, binding all three natriuretic peptides (ANP, BNP, and CNP) to regulate their levels in circulation (Pandey2021Molecular). Additionally, NPPB has been shown to activate TRPA1 channels in a concentration-dependent manner, specifically increasing the Ca2+ response in cells expressing these channels. This interaction is specific to TRPA1, as NPPB does not affect TRPV1 channels, and is inhibited by the TRPA1 channel blocker ruthenium red (Liu2010NPPB). These interactions highlight the diverse roles of NPPB in cardiovascular and other physiological processes.


## References


[1. (Giovou2024The) Alexandra E. Giovou, Monika M. Gladka, and Vincent M. Christoffels. The impact of natriuretic peptides on heart development, homeostasis, and disease. Cells, 13(11):931, May 2024. URL: http://dx.doi.org/10.3390/cells13110931, doi:10.3390/cells13110931. This article has 1 citations and is from a peer-reviewed journal.](https://doi.org/10.3390/cells13110931)

[2. (Holditch2015BType) Sara J. Holditch, Claire A. Schreiber, Ryan Nini, Jason M. Tonne, Kah-Whye Peng, Aron Geurts, Howard J. Jacob, John C. Burnett, Alessandro Cataliotti, and Yasuhiro Ikeda. B-type natriuretic peptide deletion leads to progressive hypertension, associated organ damage, and reduced survival: novel model for human hypertension. Hypertension, 66(1):199–210, July 2015. URL: http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05610, doi:10.1161/hypertensionaha.115.05610. This article has 0 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1161/HYPERTENSIONAHA.115.05610)

[3. (Tamura2000Cardiac) Naohisa Tamura, Yoshihiro Ogawa, Hideki Chusho, Kenji Nakamura, Kazuki Nakao, Michio Suda, Masato Kasahara, Ryuju Hashimoto, Goro Katsuura, Masashi Mukoyama, Hiroshi Itoh, Yoshihiko Saito, Issei Tanaka, Hiroki Otani, Motoya Katsuki, and Kazuwa Nakao. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proceedings of the National Academy of Sciences, 97(8):4239–4244, March 2000. URL: http://dx.doi.org/10.1073/pnas.070371497, doi:10.1073/pnas.070371497. This article has 473 citations.](https://doi.org/10.1073/pnas.070371497)

[4. (Rubattu2020Epigenetic) Speranza Rubattu, Rosita Stanzione, Maria Cotugno, Franca Bianchi, Simona Marchitti, and Maurizio Forte. Epigenetic control of natriuretic peptides: implications for health and disease. Cellular and Molecular Life Sciences, 77(24):5121–5130, June 2020. URL: http://dx.doi.org/10.1007/s00018-020-03573-0, doi:10.1007/s00018-020-03573-0. This article has 13 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1007/s00018-020-03573-0)

[5. (Liu2010NPPB) Kun Liu, Manoj Samuel, Melisa Ho, Richard K. Harrison, and Jeff W. Paslay. Nppb structure-specifically activates trpa1 channels. Biochemical Pharmacology, 80(1):113–121, July 2010. URL: http://dx.doi.org/10.1016/j.bcp.2010.03.005, doi:10.1016/j.bcp.2010.03.005. This article has 21 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1016/j.bcp.2010.03.005)

[6. (Pandey2021Molecular) Kailash N. Pandey. Molecular signaling mechanisms and function of natriuretic peptide receptor-a in the pathophysiology of cardiovascular homeostasis. Frontiers in Physiology, August 2021. URL: http://dx.doi.org/10.3389/fphys.2021.693099, doi:10.3389/fphys.2021.693099. This article has 24 citations and is from a peer-reviewed journal.](https://doi.org/10.3389/fphys.2021.693099)