Brain natriuretic peptide 32
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Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a
The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid
The physiologic actions of BNP are similar to those of ANP and include decrease in
Biosynthesis
BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 25-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked glycoprotein; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably furin or corin) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts.[6] Cleavage at other sites produces shorter BNP peptides with unknown biological activity.[7] Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.[8] The synthesis of BNP in cardiomyocytes is stimulated by pro-inflammatory cell factors, such as interleukin-1β, interleukin-6 and tumor necrosis factor-α.[9]
Physiologic effects
Renal
- Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases pressure in the glomerular capillaries, thus increasing the glomerular filtration rate (GFR), resulting in greater filter load of sodium and water.
- Increases blood flow through the vasa recta, which will wash the solutes (NaCl and urea) out of the medullary interstitium.[10] The lower osmolarity of the medullary interstitium leads to less reabsorption of tubular fluid and increased excretion.
- Decreases sodium reabsorption in the .
- Inhibits renin–angiotensin–aldosterone system.
Adrenal
- Reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex.
Vascular
Relaxes vascular smooth muscle in arterioles and venules by:
- Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
- Inhibition of the effects of catecholamines
Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension.[12]
Cardiac
- Inhibits maladaptive cardiac hypertrophy
- Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly[13]
- Re-expression of NPRA rescues the phenotype.
Adipose tissue
- Increases the release of free fatty acidsfrom adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
- Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
- Increases intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP-dependent protein kinase-I (cGK-I)
- Does not modulate cAMP production or PKA activity
Measurement
BNP and NT-proBNP are measured by immunoassay.[14]
Interpretation of BNP
- The main clinical utility of either BNP or NT-proBNP is that a normal level helps to rule out chronic heart failure in the emergency setting. An elevated BNP or NT-proBNP should never be used exclusively to "rule in" acute or chronic heart failure in the emergency setting due to lack of specificity [dubious ].[15]
- Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.[16]
- Increased NT-proBNP adjusted for age and sex and annual increase of NT-proBNP above 50% are associated with increased event rate in patients with non-severe aortic valve stenosis.[17]
- BNP and NT-proBNP are also typically increased in patients with left ventricular dysfunction, with or without symptoms (BNP accurately reflects current ventricular status, as its half-life is 20 minutes, as opposed to 1–2 hours for NT-proBNP).[18]
A preoperative BNP can be predictive of a risk of an acute cardiac event during vascular surgery. A
BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The achilles heel of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population.[20][21]
Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/mL
There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be an indicator of heart failure. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis.[22][23]
BNP has been suggested as a predictor for a variety of medical states, including cardiovascular mortality in diabetics[24] and cardiac impairment in cancer patients.[25][26]
BNP was found to have an important role in prognostication of heart surgery patients[27] and in the emergency department.[28] Bhalla et al. showed that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies.[29][30] Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and ESRD.[31][32][33]
The effect or race and gender on value of BNP and its utility in that context has been studied extensively.[34][35]
NYHA I | NYHA II | NYHA III | NYHA IV | |
---|---|---|---|---|
5th Percentile | 33 | 103 | 126 | 148 |
Mean | 1015 | 1666 | 3029 | 3465 |
95th Percentile | 3410 | 6567 | 10,449 | 12,188 |
The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive.[37] The BNP test is also used for the risk stratification of patients with acute coronary syndromes.[38][39]
When interpreting an elevated BNP level, values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.[40] Higher levels are seen in those with renal disease, in the absence of heart failure.
Therapeutic application
Recombinant BNP, nesiritide, has been suggested as a treatment for decompensated heart failure. However, a clinical trial failed to show a benefit of nesiritide in patients with acute decompensated heart failure.[41] Blockade of neprilysin, a protease known to degrade members of the natriuretic peptide family, has also been suggested as a possible treatment for heart failure. Dual administration of neprilysin inhibitors and angiotensin receptor blockers has been shown to be advantageous to ACE inhibitors, the current first-line therapy, in multiple settings.[42][43]
See also
- C-type natriuretic peptide – Protein-coding gene in the species Homo sapiens
References
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- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ "N-terminal-pro-BNP". LABORATORY SERVICES HANDBOOK. The University of Iowa (UIHC), Department of Pathology. 28 May 2020. Archived from the original on 2008-10-11. Showing 95th percentiles. Epic Lab Code: LAB649.
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Further reading
- Cosson S (September 2004). "Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus". Diabetes & Metabolism. 30 (4): 381–6. PMID 15525883.
- Cauliez B, Berthe MC, Lavoinne A (2005). "[Brain natriuretic peptide: physiological, biological and clinical aspects]". Annales de Biologie Clinique. 63 (1): 15–25. PMID 15689309.
- Buchner S, Riegger G, Luchner A (2005). "[Clinical utility of the cardiac markers BNP and NT-proBNP]". Acta Medica Austriaca. 31 (4): 144–51. PMID 15732251.
- LaPointe MC (June 2005). "Molecular regulation of the brain natriuretic peptide gene". Peptides. 26 (6): 944–56. S2CID 38061760.
- Hoffmann U, Borggrefe M, Brueckmann M (2006). "New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit". Critical Care. 10 (2): 134. PMID 16594987.
- Suga S, Nakao K, Hosoda K, Mukoyama M, Ogawa Y, Shirakami G, et al. (January 1992). "Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide". Endocrinology. 130 (1): 229–39. PMID 1309330.
- Kambayashi Y, Nakao K, Mukoyama M, Saito Y, Ogawa Y, Shiono S, et al. (January 1990). "Isolation and sequence determination of human brain natriuretic peptide in human atrium". FEBS Letters. 259 (2): 341–5. PMID 2136732.
- Hino J, Tateyama H, Minamino N, Kangawa K, Matsuo H (March 1990). "Isolation and identification of human brain natriuretic peptides in cardiac atrium". Biochemical and Biophysical Research Communications. 167 (2): 693–700. PMID 2138890.
- Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H (March 1989). "Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide". Biochemical and Biophysical Research Communications. 159 (3): 1427–34. PMID 2522777.
- Seilhamer JJ, Arfsten A, Miller JA, Lundquist P, Scarborough RM, Lewicki JA, et al. (December 1989). "Human and canine gene homologs of porcine brain natriuretic peptide". Biochemical and Biophysical Research Communications. 165 (2): 650–8. PMID 2597152.
- Arden KC, Viars CS, Weiss S, Argentin S, Nemer M (March 1995). "Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36". Genomics. 26 (2): 385–9. PMID 7601467.
- Weir ML, Pang SC, Flynn TG (September 1993). "Characterization of binding sites in rat for A, B and C-type natriuretic peptides". Regulatory Peptides. 47 (3): 291–305. S2CID 23098254.
- Totsune K, Takahashi K, Satoh F, Sone M, Ohneda M, Satoh C, et al. (July 1996). "Urinary immunoreactive brain natriuretic peptide in patients with renal disease". Regulatory Peptides. 63 (2–3): 141–7. S2CID 23508808.
- Totsune K, Takahashi K, Murakami O, Satoh F, Sone M, Ohneda M, et al. (September 1996). "Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors". European Journal of Endocrinology. 135 (3): 352–6. S2CID 8706854.
- Matsuo K, Nishikimi T, Yutani C, Kurita T, Shimizu W, Taguchi A, et al. (December 1998). "Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia". Circulation. 98 (22): 2433–40. PMID 9832489.
- Wiese S, Breyer T, Dragu A, Wakili R, Burkard T, Schmidt-Schweda S, et al. (December 2000). "Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length". Circulation. 102 (25): 3074–9. PMID 11120697.
- Shimizu H, Masuta K, Aono K, Asada H, Sasakura K, Tamaki M, et al. (February 2002). "Molecular forms of human brain natriuretic peptide in plasma". Clinica Chimica Acta; International Journal of Clinical Chemistry. 316 (1–2): 129–35. PMID 11750283.
- Ogawa K, Oida A, Sugimura H, Kaneko N, Nogi N, Hasumi M, et al. (February 2002). "Clinical significance of blood brain natriuretic peptide level measurement in the detection of heart disease in untreated outpatients: comparison of electrocardiography, chest radiography and echocardiography". Circulation Journal. 66 (2): 122–6. PMID 11999635.
- Asakawa H, Fukui T, Tokunaga K, Kawakami F (2002). "Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria". Journal of Diabetes and Its Complications. 16 (3): 209–13. PMID 12015190.
- Bordenave L, Georges A, Bareille R, Conrad V, Villars F, Amédée J (May 2002). "Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide". Peptides. 23 (5): 935–40. S2CID 43543051.
External links
- Brain+Natriuretic+Peptide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- BNP and NT-proBNP at Lab Tests Online
- Human NPPB genome location and NPPB gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P16860 (Natriuretic peptides B) at the PDBe-KB.
attribution: copied from