Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review

Heart failure (HF) is a primary cause of morbidity and mortality worldwide. As the most widely studied and commonly applied natriuretic peptide (NP), B-type natriuretic peptide (BNP) has the effects of diuresis, natriuresis, vasodilation, anti-hypertrophy, and anti-fibrosis and it inhibits the renin-angiotensin-aldosterone and sympathetic nervous systems to maintain cardiorenal homeostasis and counteract the effects of HF. Both BNP and N-terminal pro B-type natriuretic peptide (NT-proBNP) are applied as diagnostic, managing, and prognostic tools for HF. However, due to the complexity of BNP system, the diversity of BNP forms and the heterogeneity of HF status, there are biochemical, analytical, and clinical issues on BNP not fully understood. Current immunoassays cross-react to varying degrees with pro B-type natriuretic peptide (proBNP), NT-proBNP and various BNP forms and cannot effectively differentiate between these forms. Moreover, current immunoassays have different results and may not accurately reflect cardiac function. It is essential to design assays that can recognize specific forms of BNP, NT-proBNP, and proBNP to obtain more clinical information. Not only the processing of proBNP (corin/furin) and BNP (neprilysin), but also the effects of glycosylation on proBNP processing and BNP assays, should be targeted in future studies to enhance their diagnostic, therapeutic, and prognostic values.

[1]  A. Mebazaa,et al.  Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure. , 2014, European heart journal.

[2]  P. Collinson,et al.  Heart failure biomarkers at point-of-care: current utilization and future potential , 2014, Expert review of molecular diagnostics.

[3]  A. Wu,et al.  The effect of class-specific protease inhibitors on the stabilization of B-type natriuretic peptide in human plasma. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[4]  S. Fu,et al.  Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure , 2018, Journal of Biological Engineering.

[5]  A. Houng,et al.  Corin Overexpression Improves Cardiac Function, Heart Failure, and Survival in Mice With Dilated Cardiomyopathy , 2013, Hypertension.

[6]  A. Lambeir,et al.  Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. , 2006, Clinical chemistry.

[7]  A. G. Semenov,et al.  Human pro-B-type natriuretic peptide is processed in the circulation in a rat model. , 2011, Clinical chemistry.

[8]  Akshay S. Desai,et al.  Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure , 2015, Circulation.

[9]  A. Lerman,et al.  Secretion of prohormone of B-type natriuretic peptide, proBNP1-108, is increased in heart failure. , 2013, JACC. Heart failure.

[10]  A. Jaffe,et al.  Natriuretic Peptides and Analytical Barriers. , 2017, Clinical chemistry.

[11]  A. G. Semenov,et al.  Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases. , 2010, Clinical chemistry.

[12]  Xue-Long Sun,et al.  Glycosylation and processing of pro-B-type natriuretic peptide in cardiomyocytes. , 2011, Biochemical and biophysical research communications.

[13]  A. Jaffe,et al.  Quality specifications for B-type natriuretic peptide assays. , 2005, Clinical chemistry.

[14]  Liang Dong,et al.  Localization of corin and atrial natriuretic peptide expression in human renal segments. , 2016, Clinical science.

[15]  U. Elkayam,et al.  Angiotensin Receptor–Neprilysin Inhibition , 2017, Journal of cardiovascular pharmacology and therapeutics.

[16]  D. Hodge,et al.  Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure , 2016, European journal of heart failure.

[17]  Malte Kelm,et al.  Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. , 2015, Annals of internal medicine.

[18]  A. Luchner,et al.  Equal performance of novel N-terminal proBNP (Cardiac proBNP®) and established BNP (Triage BNP®) point-of-care tests. , 2012, Biomarkers in medicine.

[19]  W. Dole,et al.  Hypertension in mice lacking the proatrial natriuretic peptide convertase corin. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Kevin Jiang,et al.  Comparability of Results between Point-of-Care and Automated Instruments to Measure B-type Natriuretic Peptide , 2010, The western journal of emergency medicine.

[21]  J. Januzzi,et al.  Are serial BNP measurements useful in heart failure management? Serial natriuretic peptide measurements are useful in heart failure management. , 2013, Circulation.

[22]  P. Casán,et al.  N‐terminal probrain natriuretic peptide (NT‐proBNP) in the emergency diagnosis and in‐hospital monitoring of patients with dyspnoea and ventricular dysfunction , 2004, European journal of heart failure.

[23]  Lei Shen,et al.  Reduced urinary corin levels in patients with chronic kidney disease. , 2013, Clinical science.

[24]  A. Richards,et al.  Development of a BNP1-32 Immunoassay That Does Not Cross-React with proBNP. , 2017, Clinical chemistry.

[25]  J. Kosowsky,et al.  Impact of point-of-care B-type natriuretic peptide (BNP) measurement on medical decision-making for older emergency department patients with dyspnea. , 2006, The Journal of emergency medicine.

[26]  M. Emdin,et al.  Cardiac biomarker testing in the clinical laboratory: where do we stand? General overview of the methodology with special emphasis on natriuretic peptides. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[27]  Faquan Liang,et al.  Evidence for functional heterogeneity of circulating B-type natriuretic peptide. , 2007, Journal of the American College of Cardiology.

[28]  A. Jaffe,et al.  Cross-reactivity of BNP, NT-proBNP, and proBNP in commercial BNP and NT-proBNP assays: preliminary observations from the IFCC Committee for Standardization of Markers of Cardiac Damage. , 2008, Clinical chemistry.

[29]  A. Houng,et al.  Corin is co-expressed with pro-ANP and localized on the cardiomyocyte surface in both zymogen and catalytically active forms. , 2008, Journal of molecular and cellular cardiology.

[30]  R. Leduc,et al.  Cell-surface Processing of Pro-ADAMTS9 by Furin* , 2006, Journal of Biological Chemistry.

[31]  A. G. Semenov,et al.  Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site. , 2009, Clinical chemistry.

[32]  T. Funke,et al.  Insulin-degrading Enzyme Modulates the Natriuretic Peptide-mediated Signaling Response* , 2010, The Journal of Biological Chemistry.

[33]  Z. Ortutay,et al.  Genetics of the First Seven Proprotein Convertase Enzymes in Health and Disease , 2013, Current genomics.

[34]  S. Palmer,et al.  First identification of circulating prepro-A-type natriuretic peptide (preproANP) signal peptide fragments in humans: initial assessment as cardiovascular biomarkers. , 2012, Clinical chemistry.

[35]  K. Bailey,et al.  Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction. , 2011, Journal of the American College of Cardiology.

[36]  Michael Böhm,et al.  Kommentar zu den ESC-Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 , 2008, European journal of heart failure.

[37]  Efficacy and safety of a modified dosage regimen of nesiritide in patients older than 75 years with acute heart failure , 2012, Aging Clinical and Experimental Research.

[38]  A. Høiseth,et al.  Influence of glycosylation on diagnostic and prognostic accuracy of N-terminal pro-B-type natriuretic peptide in acute dyspnea: data from the Akershus Cardiac Examination 2 Study. , 2015, Clinical chemistry.

[39]  Jingjing Jiang,et al.  Ectodomain Shedding and Autocleavage of the Cardiac Membrane Protease Corin* , 2010, The Journal of Biological Chemistry.

[40]  L. A. Bonet,et al.  ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 , 2012, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[41]  J. Rehfeld,et al.  Quantification of pro-B-type natriuretic peptide and its products in human plasma by use of an analysis independent of precursor processing. , 2002, Clinical Chemistry.

[42]  K. Kostner,et al.  Circulating fragments of N-terminal pro-B-type natriuretic peptides in plasma of heart failure patients. , 2013, Clinical chemistry.

[43]  M. Putt,et al.  Simultaneous Assessment of Unprocessed ProBNP1-108 in Addition to Processed BNP32 Improves Identification of High-Risk Ambulatory Patients With Heart Failure , 2010, Circulation. Heart failure.

[44]  Fred S Apple,et al.  Immunodetection of glycosylated NT-proBNP circulating in human blood. , 2008, Clinical chemistry.

[45]  Akshay S. Desai,et al.  Angiotensin-neprilysin inhibition versus enalapril in heart failure. , 2014, The New England journal of medicine.

[46]  Claudio Passino,et al.  State of the art of immunoassay methods for B-type natriuretic peptides: An update , 2015, Critical reviews in clinical laboratory sciences.

[47]  Mario Plebani,et al.  Recommendations for the use of natriuretic peptides in acute cardiac care: a position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. , 2012, European heart journal.

[48]  L. R. Potter,et al.  ProBNP(1-108) is resistant to degradation and activates guanylyl cyclase-A with reduced potency. , 2011, Clinical chemistry.

[49]  Barry Greenberg,et al.  Primary results of the HABIT Trial (heart failure assessment with BNP in the home). , 2013, Journal of the American College of Cardiology.

[50]  Pedro Lozano Natriuretic peptides. , 2020, The Journal of the Arkansas Medical Society.

[51]  N. S. Pollitt,et al.  The precursor to B-type natriuretic peptide is an O-linked glycoprotein. , 2006, Archives of biochemistry and biophysics.

[52]  L. R. Potter,et al.  Human B-type natriuretic peptide is not degraded by meprin A. , 2010, Biochemical pharmacology.

[53]  M. Emdin,et al.  Analytical performance and diagnostic accuracy of immunometric assays for the measurement of plasma B-type natriuretic peptide (BNP) and N-terminal proBNP. , 2005, Clinical chemistry.

[54]  A. G. Semenov,et al.  Different Susceptibility of B-Type Natriuretic Peptide (BNP) and BNP Precursor (proBNP) to Cleavage by Neprilysin: The N-Terminal Part Does Matter. , 2016, Clinical chemistry.

[55]  Perry M. Elliott,et al.  ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 , 2010, European journal of heart failure.

[56]  A. G. Semenov,et al.  The brain natriuretic peptide (BNP) precursor is the major immunoreactive form of BNP in patients with heart failure. , 2007, Clinical chemistry.

[57]  Chunyi Zhang,et al.  PCSK6-mediated corin activation is essential for normal blood pressure , 2015, Nature Medicine.

[58]  M. Plebani,et al.  State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[59]  Yiqing Zhou,et al.  Corin in clinical laboratory diagnostics. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[60]  A. Jaffe,et al.  Specificity of B-Type Natriuretic Peptide Assays: Cross-Reactivity with Different BNP, NT-proBNP, and proBNP Peptides. , 2017, Clinical chemistry.

[61]  Liam M. Heaney,et al.  Prognostic Role of Molecular Forms of B-Type Natriuretic Peptide in Acute Heart Failure. , 2017, Clinical chemistry.

[62]  C. Passino,et al.  Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones. , 2011, American journal of physiology. Heart and circulatory physiology.

[63]  A. Jaffe,et al.  Comparison of Mass Spectrometry and Clinical Assay Measurements of Circulating Fragments of B-Type Natriuretic Peptide in Patients With Chronic Heart Failure , 2011, Circulation. Heart failure.

[64]  P. Erne,et al.  Long-Term Results of Intensified, N-Terminal-Pro-B-Type Natriuretic Peptide–Guided Versus Symptom-Guided Treatment in Elderly Patients With Heart Failure: Five-Year Follow-Up From TIME-CHF , 2013, Circulation. Heart failure.

[65]  M. Volpe,et al.  Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides , 2011, Journal of Molecular Medicine.

[66]  C. Ronco,et al.  Optimizing fluid management in patients with acute decompensated heart failure (ADHF): the emerging role of combined measurement of body hydration status and brain natriuretic peptide (BNP) levels , 2011, Heart Failure Reviews.

[67]  A. Maisel,et al.  Recent advances in point-of-care testing for natriuretic peptides: potential impact on heart failure diagnosis and management , 2016, Expert review of molecular diagnostics.

[68]  C. Passino,et al.  Systematic differences between BNP immunoassays: comparison of methods using standard protocols and quality control materials. , 2013, Clinica chimica acta; international journal of clinical chemistry.

[69]  R Nuti,et al.  Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure , 2010, Vascular health and risk management.

[70]  M. Redfield,et al.  Immunoreactivity and Guanosine 3′,5′-Cyclic Monophosphate Activating Actions of Various Molecular Forms of Human B-Type Natriuretic Peptide , 2007, Hypertension.

[71]  J. Burnett,et al.  Corin is present in the normal human heart, kidney, and blood, with pro-B-type natriuretic peptide processing in the circulation. , 2011, Clinical chemistry.

[72]  M. Kurusz,et al.  Efficacy and safety , 2021, Perfusion.

[73]  A. G. Semenov,et al.  Novel immunoassay for quantification of brain natriuretic peptide and its precursor in human blood. , 2008, Clinical chemistry.

[74]  B. Sarg,et al.  Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure. , 2017, Clinical chemistry.

[75]  M. Volpe,et al.  Novel Insights Into the Mechanisms Regulating Pro-Atrial Natriuretic Peptide Cleavage in the Heart and Blood Pressure Regulation: Proprotein Convertase Subtilisin/Kexin 6 Is the Corin Activating Enzyme. , 2016, Circulation research.

[76]  A. Clerico,et al.  Recent advances on natriuretic peptide system: new promising therapeutic targets for the treatment of heart failure. , 2013, Pharmacological research.

[77]  H. Kurahashi,et al.  Increased levels of soluble corin in pre-eclampsia and fetal growth restriction. , 2016, Placenta.

[78]  M. Emdin,et al.  Natriuretic peptide assays revisited: do we need pro-B-type natriuretic peptide? , 2011, Journal of the American College of Cardiology.

[79]  T. Walther,et al.  Structural substrate conditions required for neutral endopeptidase-mediated natriuretic Peptide degradation. , 2009, Journal of molecular biology.

[80]  J. Qin,et al.  Corin Variant Associated With Hypertension and Cardiac Hypertrophy Exhibits Impaired Zymogen Activation and Natriuretic Peptide Processing Activity , 2008, Circulation research.

[81]  M. Emdin,et al.  Comparison between BNP values measured in capillary blood samples with a POCT method and those measured in plasma venous samples with an automated platform , 2015, Clinical Chemistry and Laboratory Medicine.