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Published in:

01-09-2010

CD-NP: An Innovative Designer Natriuretic Peptide Activator of Particulate Guanylyl Cyclase Receptors for Cardiorenal Disease

Authors: Paul M. McKie, S. Jeson Sangaralingham, John C. Burnett Jr.

Published in: Current Heart Failure Reports | Issue 3/2010

Abstract

The natriuretic peptide (NP) family consists of structurally similar, although physiologically distinct, peptides that play an important role in cardiorenal homeostasis. CD-NP is a novel chimeric natriuretic peptide developed by the Mayo Clinic, in which the 15-amino acid COOH-terminus of dendroaspis NP is fused to C-type NP. CD-NP is a dual activator of NP receptors A and B, and therefore, possesses the strong antiproliferative and antifibrotic properties of C-type NP with the potent natriuretic, diuretic, and aldosterone-inhibiting properties of dendroaspis NP. CD-NP has favorable cardiorenal properties when compared to recombinant B-type NP (nesiritide), including preservation of glomerular filtration rate with minimal blood pressure-lowering effects. Thus, CD-NP has emerged as an appealing novel therapeutic strategy for heart failure. The endogenous NP system, the development rationale for CD-NP, as well as in vitro, animal, and human studies and future directions will be reviewed.

•• Potter LR, Abbey-Hosch S, Dickey DM: Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev 2006, 27:47–72. This comprehensive review provides detailed and up-to-date information regarding the endogenous natriuretic peptides and their receptors. CrossRefPubMed

Sudoh T, Minamino N, Kangawa K, Matsuo H: C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun 1990, 168:863–870.CrossRefPubMed

Wei CM, Aarhus LL, Miller VM, Burnett JC Jr: Action of C-type natriuretic peptide in isolated canine arteries and veins. Am J Physiol 1993, 264:H71–H73.PubMed

Schweitz H, Vigne P, Moinier D, et al.: A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps). J Biol Chem 1992, 267:13928–13932.PubMed

Schirger JA, Heublein DM, Chen HH, et al.: Presence of Dendroaspis natriuretic peptide-like immunoreactivity in human plasma and its increase during human heart failure. Mayo Clin Proc 1999, 74:126–130.CrossRefPubMed

Lisy O, Jougasaki M, Heublein DM, et al.: Renal actions of synthetic dendroaspis natriuretic peptide. Kidney Int 1999, 56:502–508.CrossRefPubMed

Burnett JC Jr, Korinek J: The tumultuous journey of nesiritide: past, present, and future. Circ Heart Fail 2008, 1:6–8.CrossRefPubMed

Korinek J, Boerrigter G, Mohammed SF, Burnett JC Jr: Insights into natriuretic peptides in heart failure: an update. Curr Heart Fail Rep 2008, 5:97–104.CrossRefPubMed

Mohammed SF, Korinek J, Chen HH, et al.: Nesiritide in acute decompensated heart failure: current status and future perspectives. Rev Cardiovasc Med 2008, 9:151–158.PubMed

10.

Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K: Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 2005, 293:1900–1905.CrossRefPubMed

11.

Witteles RM, Kao D, Christopherson D, et al.: Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 2007, 50:1835–1840.CrossRefPubMed

12.

Yancy CW, Krum H, Massie BM, et al.: Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: results of the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Circ Heart Fail 2008, 1:9–16.CrossRefPubMed

13.

Chen HH, Sundt TM, Cook DJ, et al.: Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardiopulmonary-bypass surgery: a double-blind placebo-controlled pilot study. Circulation 2007, 116 (Suppl 11):I134–I138.PubMed

14.

Mentzer RM Jr, Oz MC, Sladen RN, et al.: Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA Trial. J Am Coll Cardiol 2007, 49:716–726.CrossRefPubMed

15.

Ross JS, Chen J, Lin Z, et al.: Recent national trends in readmission rates after heart failure hospitalization. Circ Heart Fail 2010, 3:97–103.CrossRefPubMed

16.

Lee CY, Chen HH, Lisy O, et al.: Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in-human clinical trial in healthy subjects. J Clin Pharmacol 2009, 49:668–673.CrossRefPubMed

17.

• Lisy O, Huntley BK, McCormick DJ, et al.: Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP. J Am Coll Cardiol 2008, 52:60–68. This article is the first published report of CD-NP and examines the in vivo actions of CD-NP with a comparison to BNP in normal canines. CrossRefPubMed

18.

• Dickey DM, Burnett JC Jr, Potter LR: Novel bifunctional natriuretic peptides as potential therapeutics. J Biol Chem 2008, 283:35003–35009. This article provides a comprehensive assessment of CD-NP binding affinity for the natriuretic peptide receptors. CrossRefPubMed

19.

Lee CY, Lieu H, Burnett JC Jr: Designer natriuretic peptides. J Investig Med 2009, 57:18–21.PubMed

20.

Honing ML, Smits P, Morrison PJ, et al.: C-type natriuretic peptide-induced vasodilation is dependent on hyperpolarization in human forearm resistance vessels. Hypertension 2001, 37:1179–1183.PubMed

21.

Wright RS, Wei CM, Kim CH, et al.: C-type natriuretic peptide-mediated coronary vasodilation: role of the coronary nitric oxide and particulate guanylate cyclase systems. J Am Coll Cardiol 1996, 28:1031–1038.CrossRefPubMed

22.

Clavell AL, Stingo AJ, Wei CM, et al.: C-type natriuretic peptide: a selective cardiovascular peptide. Am J Physiol 1993, 264:R290–R295.PubMed

23.

Stingo AJ, Clavell AL, Aarhus LL, Burnett JC Jr: Cardiovascular and renal actions of C-type natriuretic peptide. Am J Physiol 1992, 262:H308–H312.PubMed

24.

Lewko B, Endlich N, Kriz W, et al.: C-type natriuretic peptide as a podocyte hormone and modulation of its cGMP production by glucose and mechanical stress. Kidney Int 2004, 66:1001–1008.CrossRefPubMed

25.

Hobbs A, Foster P, Prescott C, et al.: Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation 2004, 110:1231–1235.CrossRefPubMed

26.

Rose RA, Giles WR: Natriuretic peptide C receptor signalling in the heart and vasculature. J Physiol 2008, 586:353–366.CrossRefPubMed

27.

Horio T, Tokudome T, Maki T, et al.: Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts. Endocrinology 2003, 144:2279–2284.CrossRefPubMed

28.

Soeki T, Kishimoto I, Okumura H, et al.: C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. J Am Coll Cardiol 2005, 45:608–616.CrossRefPubMed

29.

Scotland RS, Ahluwalia A, Hobbs AJ: C-type natriuretic peptide in vascular physiology and disease. Pharmacol Ther 2005, 105:85–93.CrossRefPubMed

30.

• Kalra PR, Clague JR, Coats AJ, et al.: C-type natriuretic peptide production by the human kidney is blunted in chronic heart failure. Clin Sci (Lond) 2009, 118:71–77. This study, performed in humans, demonstrates CNP production in the kidneys in patients with heart failure is blunted when compared to patients without heart failure. CrossRef

31.

Johns DG, Ao Z, Heidrich BJ, et al.: Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor. Biochem Biophys Res Commun 2007, 358:145–149.CrossRefPubMed

32.

Singh G, Kuc RE, Maguire JJ, et al.: Novel snake venom ligand dendroaspis natriuretic peptide is selective for natriuretic peptide receptor-A in human heart: downregulation of natriuretic peptide receptor-A in heart failure. Circ Res 2006, 99:183–190.CrossRefPubMed

33.

Chen HH, Lainchbury JG, Burnett JC Jr: Natriuretic peptide receptors and neutral endopeptidase in mediating the renal actions of a new therapeutic synthetic natriuretic peptide dendroaspis natriuretic peptide. J Am Coll Cardiol 2002, 40:1186–1191.CrossRefPubMed

34.

Lisy O, Lainchbury JG, Leskinen H, Burnett JC Jr: Therapeutic actions of a new synthetic vasoactive and natriuretic peptide, dendroaspis natriuretic peptide, in experimental severe congestive heart failure. Hypertension 2001, 37:1089–1094.PubMed

35.

Ichiki T, Huntley BK, Sangaralingham SJ, et al.: A novel designer natriuretic peptide CD-NP suppresses TGF-beta 1 induced collagen type I production in human cardiac fibroblasts. J Card Fail 2009, 15:S34.CrossRef

36.

Lisy O, Chen HH, Burnett J: Cardiorenal actions of new designer natriuretic peptide CD-NP in experimental heart failure. J Am Coll Cardiol 2009, 53:A149.CrossRef

37.

Martin FL, Sangaralingham SJ, McKie PM, et al.: Prevention of cardiorenal fibrosis and suppression of proteinuria and aldosterone activation following experimental myocardial infarction with the novel natriuretic peptide CD-NP. J Card Fail 2009,15:S3.CrossRef

38.

Lieu H, Goldsmith S, Neutal J, et al.: Initial observations of intravenous CD-NP, chimeric natriuretic peptide, on renal functions in chronic heart failure patients. J Card Fail 2009, 15:S77.CrossRef

Title: CD-NP: An Innovative Designer Natriuretic Peptide Activator of Particulate Guanylyl Cyclase Receptors for Cardiorenal Disease
Authors: Paul M. McKie
S. Jeson Sangaralingham
John C. Burnett Jr.
Publication date: 01-09-2010
Publisher: Current Science Inc.
Published in: Current Heart Failure Reports / Issue 3/2010
Print ISSN: 1546-9530
Electronic ISSN: 1546-9549
DOI: https://doi.org/10.1007/s11897-010-0016-6

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