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• W2154855464 abstract "HomeCirculationVol. 122, No. 3A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBA New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial InfarctionWhat Does It Mean for B-Type Natriuretic Peptide and Innovative Diagnostics? Tomoko Ichiki, MD, PhD and John C. BurnettJr, MD Tomoko IchikiTomoko Ichiki From the Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn. Search for more papers by this author and John C. BurnettJrJohn C. BurnettJr From the Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn. Search for more papers by this author Originally published6 Jul 2010https://doi.org/10.1161/CIRCULATIONAHA.110.966358Circulation. 2010;122:229–232Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 6, 2010: Previous Version 1 B-type natriuretic peptide (BNP) is a cardiac-derived peptide hormone that consists of a 17-AA ring structure created by a disulfide bond joining 2 cysteine residues with distinct N and C terminal extensions. BNP binds to its particulate guanylyl cyclase receptor (GC) -A to activate the second messenger, cyclic GMP. Studies have established widespread pleuripotent actions that result in natriuresis, vasorelaxation, inhibition of renin and aldosterone, enhanced myocardial relaxation, inhibition of fibrosis and hypertrophy, promotion of cell survival, angiogenesis, and inhibition of inflammation.1,2 The clinical therapeutic potential of BNP continues to emerge, with studies demonstrating that it protects against diabetic nephropathy when genetically overexpressed by gene transfer,3 lowers blood pressure when delivered orally in experimental hypertension,4 and is cardioprotective when administered to humans undergoing cardiopulmonary bypass surgery.5Article see p 255Most recently, studies have focused on the processing of BNP from its production to its degradation. BNP is produced as a preprohormone that subsequently is processed into a prohormone by cleavage of an N-terminal signal peptide (see the Figure). Human preproBNP is a 134-AA peptide that is cleaved to the 108-AA proBNP.6 Processing of proBNP to mature BNP is mediated by corin, and a role for furin has also been implicated.7,8 Human BNP, a 32-AA peptide, is released from the myocardium in response to various physiological and pathophysiological stimuli such as myocardial wall stretch, with evidence that myocardial ischemia releases BNP.9 Once released, BNP is cleared by the natriuretic peptide clearance receptor, which is widely expressed.1 Importantly, BNP is degraded by neutral endopeptidase 24.1110 but also by dipeptidyl peptidase IV,11 the latter resulting in a novel BNP3-32, which possesses altered cardiorenal actions and may uniquely function at the tissue level as a locally acting BNP. Download figureDownload PowerPointFigure. PreproBNP amino acid sequences and processing. This figure illustrates the cleavage of BNP signal peptide reported by Siriwardena et al,19 proBNP processing into mature BNP 1–32, and its degradation to BNP3-32.Today, BNP is a widely used worldwide as a biomarker for heart failure (HF). When state-of-the-art Fourier transform ion cyclotron resonance mass spectrometry is used in human HF, much of plasma BNP immunoreactivity measured by commonly used assays is due to altered circulating molecular forms with reduced cyclic GMP–activating properties.12 We now know that BNP circulates in various forms—as its precursor proBNP1-108, as mature BNP1-32, as N-terminal peptide proBNP, and as BNP3-32. Importantly, in vitro analysis has reported that only BNP1-32 and BNP3-32 could stimulate cyclic GMP production in human cardiac fibroblasts and cardiomyocytes.13 Thus, patients with HF have low circulating “functional” BNP1-32 levels whereas other nonfunctional BNP levels, including proBNP levels, are higher than in normal subjects.12,14 This functional deficiency state of active BNP may affect the progression of HF and the remodeling process. The utility of BNP (especially proBNP1-108, mature BNP1-32 and N-terminal proBNP [NT-proBNP]) continues to grow with its use now as a prognostic biomarker for future adverse cardiovascular outcomes,15 as a guide for therapy in HF,16 and as a biomarker for myocardial injury.17,18Of great interest is the report by Siriwardena et al in the current issue of Circulation,19 which advances our knowledge of the biology of BNP as well as of its role as a biomarker for cardiovascular disease. These investigators explored the novel idea that the signal peptide of BNP (BNPsp) is secreted by the human heart and circulates in normal human subjects. They further tested the hypothesis that BNPsp would be a cardiac biomarker for the diagnosis of myocardial ischemia and injury. As noted in the Figure, BNPsp is the N-terminal 26 amino acid sequence of preproBNP1-134. As stated above, proBNP1-108 or other BNP molecular forms, with the exception of BNPsp, have been reported to circulate in humans. In the current report, the authors had the innovative thought that BNPsp is also cleaved into a C-terminal 10 amino acid BNPsp17-26 by proteolysis as signal peptides in general are degraded by a signal peptide peptidase in the endoplasmic reticulum membrane as reported previously for other preprohormones.21 They next generated a specific radioimmunoassay with their own specific antibody, which would recognize human BNPsp17-26. It is also possible that their antibody also recognizes the complete intact 26 amino acid BNPsp, a possibility that will require further studies including peptide isolation and sequence analysis.In a most comprehensive approach, Siriwardena and coworkers performed a series of studies in human myocardial tissue, in normal human subjects, and in humans with cardiovascular and renal disease. They first demonstrated that they could detect BNPsp17-26 in the extracts from human heart tissue specifically in both atrial and ventricular myocardium, and they showed that, like mature BNP1-32, BNPsp17-26 was higher in atrial myocardium. The authors then reported that BNPsp17-26 is present in the circulation in normal humans and is secreted from the normal human heart. But surprisingly, they also reported that BNPsp17-26 is secreted from the head, kidney, and lower limbs and is cleared by the liver. This observation is in stark contrast to their data in the article, which included no evidence, as determined with their NT-proBNP assay, for the secretion of mature BNP outside the heart.The meaning of these data is unclear at the moment and will require further studies. However, the data change our thinking about BNP, especially relative to its processing and possibly to where it may be produced. First, to our surprise, BNP’s signal peptide (BNPsp17-26) is secreted into the circulation. Conventional wisdom is that a signal peptide functions only intracellularly to translocate a preprohormone from site of production into the endoplasmic reticulum for processing to its prohormone and then ultimately to its release from the cell. Importantly, with rare exceptions, the signal peptide remains in the cell and is degraded and then resynthesized and used. The current article changes our thinking and suggests that a signal peptide like BNPsp17-26 is actually released and circulates. At this point, one can conclude that this secretion/release could be a nonspecific cellular release or overflow of this peptide with no specific biological meaning. Alternatively, one could ask the speculative question of where BNPsp or BNPsp17-26 has an intrinsic function. The second part of this biological BNP conundrum from the current human studies is now the possibility that BNP is synthesized outside of the heart on the basis of a step up of BNPsp17-26 levels across the head, kidney, and lower limbs in addition to the heart. This touches on the compelling concept recently advanced by Kuhn et al that BNP may be synthesized locally in ischemic tissue outside of the heart in satellite cells to induce local angiogenesis.20 Studies clearly are needed to explore possible production of BNP in these important regions of the body outside the heart and to address the new BNP biology that is provided by the findings of this important article by Siriwardena and colleagues.Most relevant from a clinical perspective is the report in the current article of circulating BNPsp17-26 levels in human ST-elevation myocardial infarction (STEMI). Specifically, the level of BNPsp17-26 is increased in human STEMI. Further, this elevation is highly specific in terms of when BNPsp17-26 levels increase relative to the phase of STEMI. The authors have found that the level of BNPsp17-26 increases only during the acute phase of STEMI (4 to 6 hours), after which it normalizes, whereas the level of NT-proBNP does not increase during this initial acute phase but only after 12 hours. Furthermore, the BNPsp17-26 level is increased before either myoglobin C or troponin I. Indeed, receiver-operating-characteristic analysis of BNPsp17-26 at 5 hours gave high sensitivity and specificity equivalent to Troponin I. The authors concluded that BNPsp17-26 might be a new and robust biomarker for early-stage myocardial infarction.Again, these most interesting observations of BNPsp17-26 in STEMI raise important questions. Why did the BNPsp17-26 level increase so rapidly with the onset of myocardial injury, preceding even other well-established biomarkers for injury such as troponin? One could speculate that BNPsp and/or BNPsp17-26 is abundant in the cardiomyocyte and with any leakiness in the cell membrane BNPsp17-26 is leaked and then normalizes as it is depleted. A more risky speculation to explain the current findings is that ischemia induces a novel secretory pathway. It should be noted that BNPsp17-26 was not elevated when first measured in patients with STEMI but increased at 4 hours after STEMI elevation, so one still cannot say that BNPsp17-26 is acutely released at the very onset of myocardial ischemia and/or injury.From the clinical perspective of biomarkers for STEMI, the current findings lay the foundation for more extensive human trials. As the authors emphasize, the current studies, with only 25 subjects, are small. A larger trial of STEMI and also acute coronary syndrome is required. Not only do we need reconfirmation of the early activation of BNPsp17-26 but we also need to define its relationship to reperfusion, to infarct size, to outcomes, and to mature BNP, NT-proBNP, proBNP, and other cardiac biomarkers. If the current findings are confirmed, then BNPsp17-26 may significantly increase our armamentarium of cardiac biomarkers for myocardial ischemia and injury.It should be stated that, surprisingly, BNPsp17-26 was not increased in the circulation in HF in contrast to NT-proBNP, BNP, or proBNP. Again, such an observation has biological and clinical relevance as well as implications for BNPsp17-26 as a biomarker. The lack of increase suggests the absence of regulated release and/or depletion of BNPsp17-26 with high rates of BNP synthesis. This lack of increase therefore excludes BNPsp17-26 as a biomarker for HF, but more studies are needed in terms of the pathogenesis of HF (ischemic versus nonischemic), severity of HF, and systolic versus diastolic HF. The elevation of plasma BNPsp17-26 in chronic kidney disease requires one statement, which is that the mechanism could be related to decreased renal clearance or more intriguingly increased renal production. Again, further studies are needed to address this interesting issue.The authors are to be congratulated for such a comprehensive study from biology to biomarkers, which significantly advances the fields of BNP and cardiac biomarkers. Conventionally, preproproteins including signal peptides, are first synthesized, and the signal peptide is recognized and deciphered by cellular sorting and translocation machinery. Preproproteins are then transported to numerous destinations, such as the nucleus, the endoplasmic reticulum, the Golgi apparatus, and the plasma membrane. Once the signal peptide is recognized, it is removed by specialized signal peptidases, and the mature part of the protein is thereby released and the divided signal peptide is then degraded by signal peptide peptidases.21 Siriwardena and coworkers provide evidence that this may not be entirely the case for preproBNP. Specifically in humans, BNPsp (or BNP17-26), the signal peptide for human preproBNP, is released from the cardiomyocyte (presumably both atrial and ventricular) and circulates. The full biological significance of this seminal observation (ie, regulation and function) remains to be defined. Of most clinical relevance is the plasma elevation of BNPsp17-26, with the acute phase of STEMI preceding standard biomarkers of myocardial injury. This key observation offers a rare opportunity for a new and novel biomarker for myocardial injury, which has the potential to enhance the care of patients with STEMI and reduce the burden of human cardiovascular disease. Thus, once again, the field of natriuretic peptides has just gotten more interesting.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Sources of FundingThis work was supported by National Institutes of Health grants PO1 HL76611 and RO1 HL36634.DisclosuresNone.FootnotesCorrespondence to John C. Burnett, Jr, MD, Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, 200 1st St SW, Rochester, MN 55905. E-mail [email protected] References 1 Potter LR, Abbey-Hosch S, Dickey DM. Natriuretic peptides, their receptors, and cyclic guanosine monophosphate–dependent signaling functions. Endocr Rev. 2006; 27: 47–72.CrossrefMedlineGoogle Scholar2 Garbers DL, Chrisman TD, Wiegn P, Katafuchi T, Albanesi JP, Bielinski V, Barylko B, Redfield MM, Burnett JC Jr. Membrane guanylyl cyclase receptors: an update. Trends Endocrinol Metab. 2006; 17: 251–258.CrossrefMedlineGoogle Scholar3 Makino H, Mukoyama M, Mori K, Suganami T, Kasahara M, Yahata K, Nagae T, Yokoi H, Sawai K, Ogawa Y, Suga S, Yoshimasa Y, Sugawara A, Tanaka I, Nakao K. Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice. Diabetologia. 2006; 49: 2514–2524.CrossrefMedlineGoogle Scholar4 Cataliotti A, Chen HH, Schirger JA, Martin FL, Boerrigter G, Costello-Boerrigter LC, James KD, Polowy K, Miller MA, Malkar NB, Bailey KR, Burnett JC Jr. Chronic actions of a novel oral B-type natriuretic peptide conjugate in normal dogs and acute actions in angiotensin II–mediated hypertension. Circulation. 2008; 118: 1729–1736.LinkGoogle Scholar5 Mentzer RM Jr, Oz MC, Sladen RN, Graeve AH, Hebeler RF Jr, Luber JM Jr, Smedira NG. Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA trial. J Am Coll Cardiol. 2007; 49: 716–726.CrossrefMedlineGoogle Scholar6 Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988; 332: 78–81.CrossrefMedlineGoogle Scholar7 Yan W, Wu F, Morser J, Wu Q. Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide–converting enzyme. Proc Natl Acad Sci U S A. 2000; 97: 8525–8529.CrossrefMedlineGoogle Scholar8 Sawada Y, Inoue M, Kanda T, Sakamaki T, Tanaka S, Minamino N, Nagai R, Takeuchi T. Co-elevation of brain natriuretic peptide and proprotein-processing endoprotease furin after myocardial infarction in rats. FEBS Lett. 1997; 400: 177–182.CrossrefMedlineGoogle Scholar9 Goetze JP, Christoffersen C, Perko M, Arendrup H, Rehfeld JF, Kastrup J, Nielsen LB. Increased cardiac BNP expression associated with myocardial ischemia. Faseb J. 2003; 17: 1105–1107.CrossrefMedlineGoogle Scholar10 Kenny AJ, Bourne A, Ingram J. Hydrolysis of human and pig brain natriuretic peptides, urodilatin, C-type natriuretic peptide and some C-receptor ligands by endopeptidase-24.11. Biochem J. 1993; 291 (Pt 1): 83–88.CrossrefMedlineGoogle Scholar11 Boerrigter G, Costello-Boerrigter LC, Harty GJ, Lapp H, Burnett JC Jr. Des-serine-proline brain natriuretic peptide 3–32 in cardiorenal regulation. Am J Physiol Regul Integr Comp Physiol. 2007; 292: R897–R901.CrossrefMedlineGoogle Scholar12 Hawkridge AM, Heublein DM, Bergen HR III, Cataliotti A, Burnett JC Jr, Muddiman DC. Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure. Proc Natl Acad Sci U S A. 2005; 102: 17442–17447.CrossrefMedlineGoogle Scholar13 Heublein DM, Huntley BK, Boerrigter G, Cataliotti A, Sandberg SM, Redfield MM, Burnett JC Jr. Immunoreactivity and guanosine 3′,5′-cyclic monophosphate activating actions of various molecular forms of human B-type natriuretic peptide. Hypertension. 2007; 49: 1114–1119.LinkGoogle Scholar14 Liang F, O'Rear J, Schellenberger U, Tai L, Lasecki M, Schreiner GF, Apple FS, Maisel AS, Pollitt NS, Protter AA. Evidence for functional heterogeneity of circulating B-type natriuretic peptide. J Am Coll Cardiol. 2007; 49: 1071–1078.CrossrefMedlineGoogle Scholar15 McKie PM, Cataliotti A, Lahr BD, Martin FL, Redfield MM, Bailey KR, Rodeheffer RJ, Burnett JC Jr. The prognostic value of N-terminal pro-B-type natriuretic peptide for death and cardiovascular events in healthy normal and stage A/B heart failure subjects. J Am Coll Cardiol. 2010; 55: 2140–2147.CrossrefMedlineGoogle Scholar16 Lainchbury JG, Troughton RW, Strangman KM, Frampton CM, Pilbrow A, Yandle TG, Hamid AK, Nicholls MG, Richards AM. N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) trial. J Am Coll Cardiol. 2009; 55: 53–60.CrossrefMedlineGoogle Scholar17 Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008; 358: 2148–2159.CrossrefMedlineGoogle Scholar18 Mukoyama M, Nakao K, Obata K, Jougasaki M, Yoshimura M, Morita E, Hosoda K, Suga S, Ogawa Y, Yasue H. Augmented secretion of brain natriuretic peptide in acute myocardial infarction. Biochem Biophys Res Commun. 1991; 180: 431–436.CrossrefMedlineGoogle Scholar19 Siriwardena M, Kleffmann T, Ruygrok P, Cameron VA, Yandle TG, Nicholls MG, Richards AM, Pemberton CJ. B-Type Natriuretic Peptide Signal Peptide Circulates in Human Blood: Evaluation as a Potential Biomarker of Cardiac Ischemia. Circulation. 2010; 122: 255–264.LinkGoogle Scholar20 Kuhn M, Volker K, Schwarz K, Carbajo-Lozoya J, Flogel U, Jacoby C, Stypmann J, van Eickels M, Gambaryan S, Hartmann M, Werner M, Wieland T, Schrader J, Baba HA. The natriuretic peptide/guanylyl cyclase–a system functions as a stress-responsive regulator of angiogenesis in mice. J Clin Invest. 2009; 119: 2019–2030.CrossrefMedlineGoogle Scholar21 Tjalsma H, Bolhuis A, Jongbloed JD, Bron S, van Dijl JM. Signal peptide–dependent protein transport in Bacillus subtilis: a genome-based survey of the secretome. Microbiol Mol Biol Rev. 2000; 64: 515–547.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Zyryanov S and Ushkalova E (2020) Comparative pharmacoeconomic analysis of medication for patients after acute decompensated heart failure, Russian Journal of Cardiology, 10.15829/1560-4071-2020-1-3690, 25:1, (65-71) Kavsak P, Hill S and Worster A (2011) Letter by Kavsak et al Regarding Article, “B-Type Natriuretic Peptide Signal Peptide Circulates in Human Blood: Evaluation as a Potential Biomarker of Cardiac Ischemia”, Circulation, 123:6, (e233-e233), Online publication date: 15-Feb-2011. July 20, 2010Vol 122, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.110.966358PMID: 20606114 Originally publishedJuly 6, 2010 KeywordsbrainEditorialsnatriuretic peptidebiological markersmyocardial infarctionPDF download Advertisement" @default.
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• W2154855464 title "A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction" @default.
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