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01.06.2011 | Main topic/CME

Neuregulin in heart failure

Reverse translation from cancer cardiotoxicity to new heart failure therapy

verfasst von: Dr. C.A. Geisberg, MD, MSCI, D.J. Lenihan, MD

Erschienen in: Herz | Ausgabe 4/2011

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Abstract

Trastuzumab is a monoclonal antibody to the ErbB2 (Her2nue) receptor over-expressed in Her2⁺ breast cancer. Trastuzumab-related cardiotoxicity has revealed the importance of ErbB2 signaling in the heart. Neuregulin (NRG-1) is an important stress-mediated paracrine growth factor that signals through the family of ErbB receptors to promote cardioprotection (myocyte cell survival, proliferation, differentiation, hypertrophy, and angiogenesis). Animal models with disrupted NRG/ErbB signaling fail to develop normally or result in impaired cardiac function post-natally. Pre-clinical animal studies and early-phase human studies suggest that recombinant NRG-1 holds promise as a new therapy for the treatment of various forms of heart failure. Much work is needed to further understand the exact mechanisms of cardiac repair and to find a safe mode of application for recombinant NRG-1 in heart failure.

Klapper LN, Glathe S, Vaisman N et al (1999) The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A 96(9):4995–5000PubMedCrossRef

Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792PubMedCrossRef

Feldman AM, Lorell BH, Reis SE (2000) Trastuzumab in the treatment of metastatic breast cancer: anticancer therapy versus cardiotoxicity. Circulation 102(3):272–274PubMed

Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2(2):127–137PubMedCrossRef

Falls DL (2003) Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 284(1):14–30PubMedCrossRef

Cote GM, Miller TA, Lebrasseur NK et al (2005) Neuregulin-1alpha and beta isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro. Exp Cell Res 311(1):135–146PubMedCrossRef

Chan R, Hardy WR, Laing MA et al (2002) The catalytic activity of the ErbB-2 receptor tyrosine kinase is essential for embryonic development. Mol Cell Biol 22(4):1073–1078PubMedCrossRef

Liu X, Hwang H, Cao L et al (1998) Domain-specific gene disruption reveals critical regulation of neuregulin signaling by its cytoplasmic tail. Proc Natl Acad Sci U S A 95(22):13024–13029PubMedCrossRef

Crone SA, Zhao YY, Fan L et al (2002) ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8(5):459–465PubMedCrossRef

10.

Lemmens K, Segers VF, Demolder M, De Keulenaer GW (2006) Role of neuregulin-1/ErbB2 signaling in endothelium-cardiomyocyte cross-talk. J Biol Chem 281(28):19469–19477PubMedCrossRef

11.

Zhao YY, Sawyer DR, Baliga RR et al (1998) Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem 273(17):10261–10269PubMedCrossRef

12.

Baliga RR, Pimental DR, Zhao YY et al (1999) NRG-1-induced cardiomyocyte hypertrophy. Role of PI-3-kinase, p70(S6 K), and MEK-MAPK-RSK. Am J Physiol 277(5 Pt 2):H2026–H2037PubMed

13.

Sawyer DB, Zuppinger C, Miller TA et al (2002) Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity. Circulation 105(13):1551–1554PubMedCrossRef

14.

Fukazawa R, Miller TA, Kuramochi Y et al (2003) Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt. J Mol Cell Cardiol 35(12):1473–1479PubMedCrossRef

15.

Russell KS, Stern DF, Polverini PJ, Bender JR (1999) Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol 277(6 Pt 2):H2205–H2211PubMed

16.

Rohrbach S, Niemann B, Silber RE, Holtz J (2005) Neuregulin receptors erbB2 and erbB4 in failing human myocardium – depressed expression and attenuated activation. Basic Res Cardiol 100(3):240–249PubMedCrossRef

17.

Uray IP, Connelly JH, Thomazy V et al (2002) Left ventricular unloading alters receptor tyrosine kinase expression in the failing human heart. J Heart Lung Transplant 21(7):771–782PubMedCrossRef

18.

Ky B, Kimmel SE, Safa RN et al (2009) Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure. Circulation 120(4):310–317PubMedCrossRef

19.

Geisberg C, Veerkamp B, Wang G et al (eds) (2010) Difference in neuregulin levels and severity of coronary artery diease. J Am Coll Cardiol Georgia World Congress Center

20.

Jabbour A, Hayward CS, Keogh AM et al (2011) Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail 13(1):83–92PubMedCrossRef

21.

Gao R, Zhang J, Cheng L et al (2010) A phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. J Am Coll Cardiol 55(18):1907–1914PubMedCrossRef

22.

Lüers C, Schmidt A, Wachter R et al (2010) Serial NT-proBNP measurements for risk stratification of patients with decompensated heart failure. Herz 35(7):488–495PubMedCrossRef

Titel: Neuregulin in heart failure
Reverse translation from cancer cardiotoxicity to new heart failure therapy
verfasst von: Dr. C.A. Geisberg, MD, MSCI
D.J. Lenihan, MD
Publikationsdatum: 01.06.2011
Verlag: Urban and Vogel
Erschienen in: Herz / Ausgabe 4/2011
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI: https://doi.org/10.1007/s00059-011-3472-1

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