Brain natriuretic peptide and N-terminal B-type natriuretic peptideogen

Brain natriuretic peptide (BNP) is mainly synthesized and secreted by ventricular myocytes and is increased during ventricular overload or dilatation, and thus can be used to reflect altered ventricular function. It is the only natural renin-angiotensin-aldosterone receptor antagonist in the body and is a specific and sensitive indicator of ventricular dysfunction. The gene encoding human BNP, NPPB, is located on chromosome 1, 1p36.2.When cardiomyocytes receive a tugging stimulus, they first secrete pre-proBNP, which is followed by the formation of proBNP, the precursor form consisting of 108 amino acids.proBNP proBNP is cleaved by endonuclease into the active cyclic polypeptide BNP of 32 amino acids, which is pro-sodium, diuretic, and vasodilator, and the biologically inactive 76 amino acids, which is NT-proBNP (N-terminal B-type lipopeptide) and is released into the circulation. bNP is mainly degraded by endonuclease in the lungs and kidneys, or cleared by endoreceptors in the blood vessels, whereas NT-proBNP is mainly excreted via the kidneys. BNP has a shorter half-life and can respond to changes in a patient's condition; NT-proBNP has a longer, more stable half-life.BNP and NT-proBNP (i.e., the biologically inactive N-terminal portion of the prohormone) are rapid and sensitive biomarkers for the diagnosis of heart failure.BNP and NT-proBNP can be measured simultaneously in the blood and the bloodstream.BNP and NT-proBNP can be measured in the blood and the bloodstream. Simultaneous measurement of BNP or NT-proBNP levels in the blood pressure allows for the diagnosis and evaluation of heart failure.

Formation of BNP and NT-proBNP

Brain natriuretic peptide (BNP), a member of the family of three natriuretic peptides secreted mainly by the heart, has a common ring structure consisting of 17 amino acids linked by disulfide bonds, regulates the self-stabilizing balance of blood pressure and blood volume, and has diuretic effects. Most BNP is present in cardiomyocytes as BNP-32 and is secreted in the body of patients who develop heart failure, renal failure, some forms of secondary hypertension, and liver disease.

Pre-Pro-BNP is originally a complex structure of 134 amino acids. The amino-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) is a single peptide with a straight-chain structure that is secreted by the ventricles and has an overall straight-chain structure of 76 amino acids. The predominant form of BNP is the cyclic structure containing a specific The main form of BNP is a 32-peptide containing a specific cyclic structure in which the 7th and 23rd residues at the amino-terminal end are formed by disulfide bonds to form a cyclic structure; the synthesis pathway of BNP and NT-proBNP is as follows: high expression of the BNP gene is rapidly stimulated only when ventricular wall tension is increased, and ventricular myocytes synthesize a large amount of BNP and secrete it into the bloodstream. Pro-natriuretic peptide B-primary enters the rough endoplasmic reticulum and is transformed into pro-natriuretic peptide B-primary (proBNP) by glycosylation and enzymatic excision of the leading peptide. proBNP, after it enters into the bloodstream, is further degraded into biologically active BNP (C-terminal fragment of 32 amino acids) and inactive dNT-proBNP (N-terminal fragment of 76 amino acids).

Distribution and clearance of BNP

BNP is widely distributed in the brain, spinal cord, heart, lungs, and other tissues, with the heart being the most abundant. BNP is mainly found in the left and right atria, with the right atrium containing more than three times the amount of the left atrium, and the ventricle containing less than 1/20 the amount of the atrium.BNP is cleared from the bloodstream by two mechanisms, one of which is through C-type BNP. One is through C-type BNP receptor-mediated cellular uptake followed by degradation in lysosomes; the other pathway is degradation by neutral endopeptidases on the cell membrane surface. NT-proBNP, the precursor terminus of brain natriuretic peptide, is almost unaffected by neutral endopeptidase. Therefore, in patients taking drugs that inhibit neutral endopeptidase activity, NT-proBNP is a more objective indicator of cardiovascular function than BNP.

Protein characteristics: NT-proBNP is encoded by the NPPB gene on chromosome 1 and is synthesized and secreted extracellularly by ventricular myocytes. 134 amino acid pro-natriuretic peptide B proteins are transcribed from the NPPB gene. 8600 Da; 3-108aa is proBNP (B-type natriuretic peptide proximate), with a relative molecular mass of about 12000 Da; and 103-134aa is BNP (brain natriuretic peptide), with a relative molecular mass of about 3200 Da.

Figure 1 The process of BNP formation                   Figure 2 Schematic diagram of

BNP molecular structure

Biological functions of BNP and NT-proBNP

Brain natriuretic peptide (BNP) and N-terminal B-type natriuretic peptide (NT-proBNP) are both commonly used diagnostic markers for heart failure. Although both are synthesized and secreted by cardiomyocytes, their physiological functions are very different.

BNP has important biological significance, it can promote sodium excretion, urinary excretion, strong vasodilatory effect, can counteract the vasoconstrictor effect of the renin-angiotensin-aldosterone system (RAAS), and is a major endocrine system in the human body to resist volume overload and hypertension, as is ANP.

{C}(1) {C}BNP affects circulatory blood pressure by different mechanisms, antagonizing the action of the renin-angiotensin-aldosterone system as well as feedback regulating the activity of cardiovascular centers in the brain, lowering the threshold of vagal efferent impulses thereby inhibiting the tachycardia reflex and vasoconstriction, and increasing coronary and renal blood flow.

{C}(2) {C}B increases glomerular filtration rate and promotes urination by inhibiting the release of renin from dense plaques in the periglomerular apparatus of the glomerular entry arterioles and inhibiting the synthesis and release of aldosterone from the cells of the globular zona glomerulosa of the adrenal cortex. Its natriuretic and diuretic effects are further enhanced by increased water and sodium excretion from renal distal tubules and decreased reabsorption of water and sodium from collecting ducts. When heart failure, renal failure, cirrhosis ascites, and other excessive absorption of body fluids or salts produce edematous disorders resulting in increased atrial or ventricular volume load and increased lateral wall pressure, natriuretic peptide hormone release increases.

{C}(3) {C}Lowering systemic and pulmonary vascular resistance and systemic and pulmonary vascular blood pressure (preload), lowering venous return flow (afterload), lowering atrial and ventricular end-diastolic pressure, etc., increasing cardiac output, and improving diastolic function.

(4) Regulate the process of cardiovascular cell proliferation and hypertrophy. Blocking ANP, BNP gene expression, or binding of ANP, BNP to its receptor leads to increased blood pressure and myocardial hypertrophy with impaired renal responsiveness to volume loading.BNP is also considered to be an anti-fibrotic factor derived from cardiomyocytes.

Advantages of NT-proBNP as a marker of heart failure:

NT-proBNPN-terminal B-type natriuretic peptide proteins (NT-proBNP) have an overall straight-chain structure, are biologically inactive, and are stretched by cardiomyocytes to enter the blood cells and are cleared by the kidneys. The half-life is 90-120 min, and it is stable in vitro; it is cleared slowly in the blood and can accumulate higher concentrations, and the concentration in the blood is positively correlated with the degree of cardiac dysfunction; the level of NT-proBNP is not affected by factors such as body position and daily activities, and there is no intra- or inter-day fluctuation, and it has good reproducibility. Therefore, NT-proBNP is the gold standard among heart failure markers. Compared with BNP, NT-proBNP, has a long half-life, high blood concentration, stability and anti-interference.

The inventory of reagents associated with terminal B-type natriuretic peptide pro (NT-proBNP) that KMD Bioscience can offer:

KMD Bioscience, as a supplier of in vitro diagnostic raw materials, is committed to the rapid development and large-scale production of proteins and antibodies for in vitro diagnostics. KMD Bioscience has successfully developed many recombinant proteins, antibodies, antibody-drug target proteins, industrial enzymes, diagnostic raw materials, and other related reagents for scientific research and drug discovery. KMD Bioscience adheres to independent innovation, constantly breaks through key technologies, has obtained national patent pilot units and laboratories ISO9001:2015 quality management system certification and adhere to continuous optimization, effectively ensuring the quality stability of products in the production process and final delivery.