Brain natriuretic peptides

from Wikipedia, the free encyclopedia
Natriuretic peptide type B
Natriuretic peptide type B
BNP with ANP receptor according to PDB  1YK1
Properties of human protein
Mass / length primary structure 32 amino acids; 3.47 kDa
Precursor preproBNP (134 amino acids; 14.7 kDa)
Identifier
Gene names NPPB  ; BNP-32
External IDs
Drug information
ATC code C01 DX19
DrugBank DB04899
Drug class hormone
Occurrence
Parent taxon Eutheria ( Euteleostomi )
Orthologue
human Beef
Entrez 4879 508734
Ensemble ENSG00000120937
UniProt P16860 P13204
Refseq (mRNA) NM_002521
Refseq (protein) NP_002512 XP_585559
Gene locus Chr 1: 11.84 - 11.84 Mb
PubMed search 4879 508734

The brain natriuretic peptides ( BNP ) (also B-type natriuretic peptide or natriuretic peptide type B is called), a hormone that formed upon stretching of the ventricles of the heart muscle cells and secreted ( secreted ) is. BNP is used as a diagnostic marker and for the treatment of heart failure (heart muscle weakness). The term “brain” goes back to the fact that BNP was detected in the brain of pigs and in small amounts also in the human brain .

Biochemistry and physiology

BNP is a 32 amino acid protein synthesized primarily in the myocardium. It is derived from an inactive precursor protein ( proBNP ) comprising 108 amino acids . This is split intracellularly into 2 fragments, BNP and NTproBNP ( N-terminal pro-B-type natriuretic peptide ) comprising 76 amino acids . There are many indications that NT-proBNP in the blood and both by thoracentesis recoverable pleural effusion is a diagnostically even more sensitive marker for acute heart failure.

BNP is a vasodilatory messenger substance. The physiological effect of BNP is mediated via the A receptor, which functions as a membrane-bound guanylyl cyclase . Its activation leads to increased formation of cGMP and, via the downstream signaling pathways, to a decrease in the intracellular calcium concentration. This leads to the relaxation of the smooth muscles and a reduction in preload and afterload. The natriuretic peptides thus represent an antagonist to the vasoconstrictive angiotensin II . BNP also acts in the kidneys , where it promotes sodium and urine excretion ( natriuretic and diuretic ). The degradation of BNP takes place via the enzyme neutral endopeptidase (NEP) and via the C receptor.

Diagnosis

The level of the BNP concentration in the blood correlates well with the severity of the heart failure. BNP and NT-proBNP can be detected in the blood using different measurement methods. Rapid tests for clinical use are now also available. The European Society for Cardiology gives normal values ​​for BNP <100 pg / ml and for NT-proBNP values ​​of <63 to <738 pg / ml, which are strongly dependent on age and sex.

Basically, the BNP increases with age in both sexes, but newborns also have significantly higher values. The measurement of the BNP for the differential diagnosis of heart failure has been incorporated into the guidelines of the European and German Society for Cardiology and the German Society for Pediatric Cardiology.

NYHA classification BNP (median in ng / l) NT-proBNP (median in ng / l)
NYHA stage I. 150 340
NYHA stage II 340 950
NYHA stage III 590 1570
NYHA stage IV 950 1710

pharmacology

Nesiritide is a recombinant human BNP with an identical structure and a similar mechanism of action as the endogenous BNP. It leads cell receptor-mediated via activation of guanylate cyclase to an increase of intracellular cGMP with consecutive diuresis and vasodilation. Nesiritide is approved in the USA under the trade name Natrecor® for the relief of shortness of breath in patients with acute heart failure. The clinical significance of recombinant BNP therapy for decompensated heart failure cannot, however, be conclusively assessed in view of the latest study results.

Fat metabolism

NPR-A receptors for natriuretic peptides and NPR-C receptors, which have a peptide-eliminating effect, are also found on fat cells . There they stimulate lipolysis . Overexpression of BNP protects mice from obesity and glucose intolerance , even with high fat food. Likewise show knockout mice , which the abbauinitiierende receptor NPR-C is missing, thus resulting increase in BNP levels comprise a reduced fat mass and an increased expression of genes typical of brown fat cells are, in turn, to an increased energy requirement and thermogenesis responsible are. If mice were treated with BNP infusions, this led to an activation of brown adipose tissue, but also to a new expression of “brown” adipose cell genes in white adipose cells, which is known as browning . This in turn resulted in an increased need for oxygen and increased energy consumption. An increased BNP release with corresponding thermogenesis and increased energy consumption was also observed during weight loss, muscular exercise and exposure to cold. Several studies show lower BNP levels in overweight patients who are insulin resistant.

Thus, in addition to its classic effect as a natriuretic, diuretic and vasodilator, at least in animal experiments, BNP also leads to increased energy consumption and increased thermogenesis via lipolysis, activation of brown fat cells and browning white fat cells. Possibly the BNP is the molecular mediator of positive metabolic effects when changing habits ( lifestyle modification ).

literature

Individual evidence

  1. ↑ Q. Zhou, ZJ Ye et al. a .: Diagnostic value of N-terminal pro-brain natriuretic peptide for pleural effusion due to heart failure: a meta-analysis. In: Heart . Volume 96, Number 15, August 2010, pp. 1207-1211. doi: 10.1136 / hrt.2009.188474 . PMID 20511623 . (Review).
  2. ↑ S. Janda, J. Swiston: Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin: a systematic review and meta-analysis. In: BMC pulmonary medicine. Volume 10, 2010, p. 58, ISSN  1471-2466 . doi: 10.1186 / 1471-2466-10-58 . PMID 21092122 . PMC 2994800 (free full text). (Review).
  3. ↑ a b Yasue et al .: Localization and Mechanism of Secretion of B-Type Natriuretic Peptide in Comparison With Those of A-Type Natriuretic Peptide in Normal Subjects and Patients With Heart Failure . In: Circulation . 1994, 90, pp. 195-203.
  4. ↑ Weil, Schunkert: Pathophysiology of chronic heart failure . In: Clinical Research in Cardiology , Suppl 4, 2006, 95, pp. 1-17
  5. ↑ a b Dickstein et al .: ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008 . In: European Heart Journal , 2008, 29, pp. 2388-2442
  6. ↑ Prof. Dr. med. J. Blessing, et al .: NT-proBNP - a valuable parameter for diagnosis and monitoring of the progression of heart failure . Ed .: Laborärzte Singen. ( labor-blessing.de [PDF]).
  7. ↑ Mir et al .: Pediatrics , 2003 Oct, 112, pp. 896-899
  8. ↑ Mir et al .: Pediatr Cardiol. , 2006 Jan-Feb, 27 (1), pp. 73-77
  9. ^ German Society for Cardiology: Guidelines for the Therapy of Chronic Heart Failure . (PDF) In: Journal of Cardiology . 94, No. 8, 2005, pp. 488-509. Retrieved April 9, 2009.
  10. ↑ Andreas Luchner, Stephan Holmer, Heribert Schunkert, Günter A. Riegger: Significance of the heart failure markers BNP and NT-proBNP for the clinic . Deutsches Ärzteblatt, vol. 100, issue 50, December 12, 2003, A3314 - A3321
  11. ↑ a b N Gassanov et al .: Natriuretic peptides in the therapy of acute decompensated heart failure . In: Dtsch Med Wochenschr . 2011 Aug, 136 (34-35), pp. 1738-1743, PMID 21877307
  12. ↑ Natig Gassanov, Esther Biesenbach, Evren Caglayan, Amir Nia, Uwe Fuhr, Fikret Er: Natriuretic peptides in therapy for decompensated heart failure . In: European Journal of Clinical Pharmacology , Volume 68, Number 3, 2012, pp. 223-230
  13. ↑ Thomas J. Wang: The Natriuretic Peptides and Fat Metabolism . In: The New England Journal of Medicine , 2012, 367, pp. 377-378