Brain natriuretic peptide

Natriuretic peptide B
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsNPPB ; BNP
External IDsOMIM: 600295 HomoloGene: 81698 GeneCards: NPPB Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez4879n/a
EnsemblENSG00000120937n/a
UniProtP16860n/a
RefSeq (mRNA)NM_002521n/a
RefSeq (protein)NP_002512n/a
Location (UCSC)Chr 1:
11.92 – 11.92 Mb		n/a
PubMed searchn/a

Brain natriuretic peptide (BNP), now known as B-type natriuretic peptide or Ventricular Natriuretic Peptide (still BNP), is a 32-amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes). The release of BNP is modulated by calcium ions.[1] BNP is named as such because it was originally identified in extracts of porcine brain, although in humans it is produced mainly in the cardiac ventricles.

BNP is secreted along with a 76-amino acid N-terminal fragment (NT-proBNP) that is biologically inactive. BNP binds to and activates the atrial natriuretic factor receptors NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.

The physiologic actions of BNP are similar to those of ANP and include decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. Thus, the net effect of BNP and ANP is a decrease in blood volume, which lowers systemic blood pressure and afterload, yielding an increase in cardiac output, partly due to a higher ejection fraction.

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.[2] Cleavage at other sites produces shorter BNP peptides with unknown biological activity.[3] Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.[4]

Clinical significance

BNP can be elevated in renal failure. 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.[8][9]

Measurement

BNP and NT-proBNP are measured by immunoassay.[10]

BNP less than 100 pg per milliliter

BNP less than 50 pg per milliliter

The effect or race and gender on value of BNP and its utility in that context has been studied extensively.[21][22]

NT-proBNP levels (in pg/mL) by NYHA functional class [23]
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.[24] The BNP test is also used for the risk stratification of patients with acute coronary syndromes.[25][26]

When interpreting an elevated BNP level, it is useful to remember that values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.[27] Higher levels are seen in those with renal disease, in the absence of heart failure.

Therapeutic application

Recombinant BNP, nesiritide, is used to treat decompensated heart failure. However, a recent clinical trial[28] failed to show a benefit of nesiritide in patients with acute decompensated heart failure, and the authors could not recommend its use.

See also

References

  1. ↑ Ziskoven D, Forssmann WG, Holthausen U, Menz G, Addicks K, Rippegater G (1989). "Calcium Calmodulin antagonists Influences the release of Cardiodilatin/ANP from Atrial Cardiocytes". In Kaufmann W, Wambach G. Handbook Endocrinology of the Heart. Berlin: Verlag: Springer. pp. 233–4. ISBN 978-3-540-51409-1.
  2. ↑ Schellenberger U, O'Rear J, Guzzetta A, Jue RA, Protter AA, Pollitt NS (July 2006). "The precursor to B-type natriuretic peptide is an O-linked glycoprotein". Arch. Biochem. Biophys. 451 (2): 160–6. doi:10.1016/j.abb.2006.03.028. PMID 16750161.
  3. ↑ Niederkofler EE, Kiernan UA, O'Rear J, Menon S, Saghir S, Protter AA, Nelson RW, Schellenberger U (November 2008). "Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure". Circ Heart Fail 1 (4): 258–64. doi:10.1161/CIRCHEARTFAILURE.108.790774. PMID 19808300.
  4. ↑ Semenov AG, Postnikov AB, Tamm NN, Seferian KR, Karpova NS, Bloshchitsyna MN, Koshkina EV, Krasnoselsky MI, Serebryanaya DV, Katrukha AG (March 2009). "Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site". Clin. Chem. 55 (3): 489–98. doi:10.1373/clinchem.2008.113373. PMID 19168558.
  5. ↑ Maisel A, Krishnaswamy P, Nowak R, McCord J, Hollander J, Duc P, Omland T, Storrow A, Abraham W, Wu A, Clopton P, Steg P, Westheim A, Knudsen C, Perez A, Kazanegra R, Herrmann H, McCullough P (2002). "Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure". N Engl J Med 347 (3): 161–7. doi:10.1056/NEJMoa020233. PMID 12124404.
  6. ↑ Bhalla V, Willis S, Maisel AS (2004). "B-type natriuretic peptide: the level and the drug--partners in the diagnosis of heart failure". Congest Heart Fail 10 (1 Suppl 1): 3–27. doi:10.1111/j.1527-5299.2004.03310.x. PMID 14872150.
  7. ↑ Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS (September 2004). "A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction". Am. Heart J. 148 (3): 518–23. doi:10.1016/j.ahj.2004.03.014. PMID 15389242.
  8. ↑ Austin WJ, Bhalla V, Hernandez-Arce I, Isakson SR, Beede J, Clopton P, Maisel AS, Fitzgerald RL (October 2006). "Correlation and prognostic utility of B-type natriuretic peptide and its amino-terminal fragment in patients with chronic kidney disease". Am. J. Clin. Pathol. 126 (4): 506–12. doi:10.1309/M7AAXA0J1THMNCDF. PMID 16938661.
  9. ↑ Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Maisel AS (May 2006). "How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study". Am. Heart J. 151 (5): 999–1005. doi:10.1016/j.ahj.2005.10.011. PMID 16644321.
  10. ↑ Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, Zucchelli GC, Plebani M (December 2012). "State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study". Clin. Chim. Acta 414: 112–9. doi:10.1016/j.cca.2012.07.017. PMID 22910582.
  11. ↑ Strunk A, Bhalla V, Clopton P, Nowak RM, McCord J, Hollander JE, Duc P, Storrow AB, Abraham WT, Wu AH, Steg G, Perez A, Kazanegra R, Herrmann HC, Aumont MC, McCullough PA, Maisel A (January 2006). "Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study". Am. J. Med. 119 (1): 69.e1–11. doi:10.1016/j.amjmed.2005.04.029. PMID 16431187.
  12. ↑ Brenden CK, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R, Maisel AS (May 2006). "Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study". Am. Heart J. 151 (5): 1006–11. doi:10.1016/j.ahj.2005.10.017. PMID 16644322.
  13. ↑ Bhalla MA, Chiang A, Epshteyn VA, Kazanegra R, Bhalla V, Clopton P, Krishnaswamy P, Morrison LK, Chiu A, Gardetto N, Mudaliar S, Edelman SV, Henry RR, Maisel AS (September 2004). "Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus". J. Am. Coll. Cardiol. 44 (5): 1047–52. doi:10.1016/j.jacc.2004.05.071. PMID 15337217.
  14. ↑ Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS (May 2004). "Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery". J. Am. Coll. Cardiol. 43 (10): 1873–9. doi:10.1016/j.jacc.2003.12.048. PMID 15145114.
  15. ↑ Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R (September 2004). "Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath". J. Am. Coll. Cardiol. 44 (6): 1328–33. doi:10.1016/j.jacc.2004.06.015. PMID 15364340.
  16. ↑ Bhalla V, Isakson S, Bhalla MA, Lin JP, Clopton P, Gardetto N, Maisel AS (February 2005). "Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients". Am. J. Hypertens. 18 (2 Pt 2): 73S–81S. doi:10.1016/j.amjhyper.2004.11.044. PMID 15752936.
  17. ↑ Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS (February 2009). "B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events". J. Card. Fail. 15 (1): 41–7. doi:10.1016/j.cardfail.2008.09.003. PMID 19181293.
  18. ↑ Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A (August 2005). "Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women". Am. J. Obstet. Gynecol. 193 (2): 450–4. doi:10.1016/j.ajog.2004.12.006. PMID 16098869.
  19. ↑ Bhalla V, Bhalla MA, Maisel AS (August 2004). "Evolution of B-type natriuretic peptide in evaluation of intensive care unit shock". Crit. Care Med. 32 (8): 1787–9. doi:10.1097/01.CCM.0000135748.75590.54. PMID 15286561.
  20. ↑ Sheen V, Bhalla V, Tulua-Tata A, Bhalla MA, Weiss D, Chiu A, Abdeen O, Mullaney S, Maisel A (February 2007). "The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease". Am. Heart J. 153 (2): 244.e1–5. doi:10.1016/j.ahj.2006.10.041. PMID 17239684.
  21. ↑ Maisel AS, Clopton P, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg G, Westheim A, Knudsen CW, Perez A, Kazanegra R, Bhalla V, Herrmann HC, Aumont MC, McCullough PA (June 2004). "Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study". Am. Heart J. 147 (6): 1078–84. doi:10.1016/j.ahj.2004.01.013. PMID 15199359.
  22. ↑ Daniels LB, Bhalla V, Clopton P, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Jesse R, Maisel A (May 2006). "B-type natriuretic peptide (BNP) levels and ethnic disparities in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision making in patients presenting with shortness of breath". J. Card. Fail. 12 (4): 281–5. doi:10.1016/j.cardfail.2006.01.008. PMID 16679261.
  23. ↑ "N-terminal pro-BNP".
  24. ↑ Lam LL, Cameron PA, Schneider HG, Abramson MJ, Müller C, Krum H (December 2010). "Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting". Ann. Intern. Med. 153 (11): 728–35. doi:10.7326/0003-4819-153-11-201012070-00006. PMID 21135296.
  25. ↑ Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA (January 2007). "N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease". JAMA 297 (2): 169–76. doi:10.1001/jama.297.2.169. PMC 2848442. PMID 17213400.
  26. ↑ Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, Maisel AS (September 2005). "Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure". Am. Heart J. 150 (3): 471–7. doi:10.1016/j.ahj.2004.11.021. PMID 16169326.
  27. ↑ Wang TJ, Larson MG, Levy D et al. (2004). "Impact of obesity on plasma natriuretic peptide levels". Circulation. 109 (5): 594–600. doi:10.1161/01.CIR.0000112582.16683.EA. PMID 14769680.
  28. ↑ O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ et al. (July 2011). "Effect of nesiritide in patients with acute decompensated heart failure". N. Engl. J. Med. 365 (1): 32–43. doi:10.1056/NEJMoa1100171. PMID 21732835.

Further reading

  • Cosson S (2004). "Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus". Diabetes Metab. 30 (4): 381–6. doi:10.1016/S1262-3636(07)70132-5. PMID 15525883.
  • Cauliez B, Berthe MC, Lavoinne A (2005). "[Brain natriuretic peptide: physiological, biological and clinical aspects]". Ann. Biol. Clin. (Paris) 63 (1): 15–25. PMID 15689309.
  • Buchner S, Riegger G, Luchner A (2005). "[Clinical utility of the cardiac markers BNP and NT-proBNP]". Acta Med. Austriaca 31 (4): 144–51. PMID 15732251.
  • LaPointe MC (2005). "Molecular regulation of the brain natriuretic peptide gene". Peptides 26 (6): 944–56. doi:10.1016/j.peptides.2004.08.028. PMID 15911064.
  • 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 (London, England) 10 (2): 134. doi:10.1186/cc4883. PMC 1550883. PMID 16594987.
  • Suga S, Nakao K, Hosoda K et al. (1992). "Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide". Endocrinology 130 (1): 229–39. doi:10.1210/en.130.1.229. PMID 1309330.
  • Kambayashi Y, Nakao K, Mukoyama M et al. (1990). "Isolation and sequence determination of human brain natriuretic peptide in human atrium". FEBS Lett. 259 (2): 341–5. doi:10.1016/0014-5793(90)80043-I. PMID 2136732.
  • Hino J, Tateyama H, Minamino N et al. (1990). "Isolation and identification of human brain natriuretic peptides in cardiac atrium". Biochem. Biophys. Res. Commun. 167 (2): 693–700. doi:10.1016/0006-291X(90)92081-A. PMID 2138890.
  • Sudoh T, Maekawa K, Kojima M et al. (1989). "Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide". Biochem. Biophys. Res. Commun. 159 (3): 1427–34. doi:10.1016/0006-291X(89)92269-9. PMID 2522777.
  • Seilhamer JJ, Arfsten A, Miller JA et al. (1990). "Human and canine gene homologs of porcine brain natriuretic peptide". Biochem. Biophys. Res. Commun. 165 (2): 650–8. doi:10.1016/S0006-291X(89)80015-4. PMID 2597152.
  • Arden KC, Viars CS, Weiss S et al. (1995). "Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36". Genomics 26 (2): 385–9. doi:10.1016/0888-7543(95)80225-B. PMID 7601467.
  • Weir ML, Pang SC, Flynn TG (1993). "Characterization of binding sites in rat for A, B and C-type natriuretic peptides". Regul. Pept. 47 (3): 291–305. doi:10.1016/0167-0115(93)90396-P. PMID 7901875.
  • Totsune K, Takahashi K, Satoh F et al. (1996). "Urinary immunoreactive brain natriuretic peptide in patients with renal disease". Regul. Pept. 63 (2–3): 141–7. doi:10.1016/0167-0115(96)00035-3. PMID 8837222.
  • Totsune K, Takahashi K, Murakami O et al. (1996). "Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors". Eur. J. Endocrinol. 135 (3): 352–6. doi:10.1530/eje.0.1350352. PMID 8890728.
  • Matsuo K, Nishikimi T, Yutani C et al. (1999). "Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia". Circulation 98 (22): 2433–40. doi:10.1161/01.CIR.98.22.2433. PMID 9832489.
  • Wiese S, Breyer T, Dragu A et al. (2001). "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. doi:10.1161/01.CIR.102.25.3074. PMID 11120697.
  • Shimizu H, Masuta K, Aono K et al. (2002). "Molecular forms of human brain natriuretic peptide in plasma". Clin. Chim. Acta 316 (1–2): 129–35. doi:10.1016/S0009-8981(01)00745-8. PMID 11750283.
  • Ogawa K, Oida A, Sugimura H et al. (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". Circ. J. 66 (2): 122–6. doi:10.1253/circj.66.122. 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". J. Diabetes Complicat. 16 (3): 209–13. doi:10.1016/S1056-8727(01)00173-8. PMID 12015190.
  • Bordenave L, Georges A, Bareille R et al. (2003). "Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide". Peptides 23 (5): 935–40. doi:10.1016/S0196-9781(02)00004-9. PMID 12084525.

External links