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Current Heart Failure Reports

Erschienen in:

01.06.2014 | Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors (SD Katz, Section Editor)

Neuregulin-1 Signaling in the Pathogenesis of Chemotherapy-Induced Heart Failure

verfasst von: Carrie Geisberg Lenneman

Erschienen in: Current Heart Failure Reports | Ausgabe 2/2014

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Abstract

The National Cancer Institute estimates that approximately 13.7 million Americans with a history of cancer were alive on January 1, 2012. With the rising number of cancer survivors, there is an increased focus on how chemotherapy agents modulate the cardiovascular biology and cause chemotherapy-related heart failure in certain patients. Neuregulin-1 (NRG-1) is an important cardiac growth factor that is essential for normal myocardial development and maintenance. Certain chemotherapy agents perturb the normal NRG-1 signaling in the cardiovascular system and cause cardiac dysfunction and, in some cases, symptomatic heart failure. As researchers have learned the critical importance of NRG-1 within the cardiovascular system, more attention has been focused on the potential use of NRG-1 as biomarker and therapy for the treatment of heart failure. This review will highlight the biology of NRG-1 within the cardiovascular system, its role in chemotherapy-induced heart failure, and the translational potential of NRG-1 as treatment for heart failure.

Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.PubMedCrossRef

Pentassuglia L, Sawyer DB. The role of Neuregulin-1 beta/ErbB signaling in the heart. Exp Cell Res. 2009;315:627–37.PubMedCentralPubMedCrossRef

Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature. 1995;378:386–90.PubMedCrossRef

Lee KF, Simon H, Chen H, Bates B, Hung MC, Hauser C. Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature. 1995;378:394–8.PubMedCrossRef

Fuller SJ, Sivarajah K, Sugden PH. ErbB receptors, their ligands, and the consequences of their activation and inhibition in the myocardium. J Mol Cell Cardiol. 2008;44:831–54.PubMedCrossRef

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

Gassmann M, Casagranda F, Orioli D, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378:390–4.PubMedCrossRef

Rentschler S, Zander J, Meyers K, et al. Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U S A. 2002;99:10464–9.PubMedCentralPubMedCrossRef

Crone SA, Zhao YY, Fan L, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8:459–65.PubMedCrossRef

10.

Sawyer DB, Zuppinger C, Miller TA, Eppenberger HM, Suter TM. Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity. Circulation. 2002;105:1551–4.PubMedCrossRef

11.

Kuramochi Y, Cote GM, Guo XX, et al. Cardiac endothelial cells regulate reactive oxygen species-induced cardiomyocyte apoptosis through neuregulin-1 beta/erbB4 signaling. J Biol Chem. 2004;279:51141–7.PubMedCrossRef

12.

Lebrasseur NK, Cote GM, Miller TA, Fielding RA, Sawyer DB. Regulation of neuregulin/ErbB signaling by contractile activity in skeletal muscle. Am J Physiol Cell Physiol. 2003;284:C1149–55.PubMedCrossRef

13.

Russell KS, Stern DF, Polverini PJ, Bender JR. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol. 1999;277:H2205–11.PubMed

14.

Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature. 2002;416:279–80.PubMedCrossRef

15.

Lange T, Nentwich MF, Luth M, Yekebas E, Schumacher U. Trastuzumab has anti-metastatic and anti-angiogenic activity in a spontaneous metastasis xenograft model of esophageal adenocarcinoma. Cancer Lett. 2011;308:54–61.PubMedCrossRef

16.

Moondra V, Sarma S, Buxton T, et al. Serum Neuregulin-1beta as a Biomarker of Cardiovascular Fitness. Open Biomark J. 2009;2:1–5.PubMedCentralPubMedCrossRef

17.

Ky B, Kimmel SE, Safa R, et al. Circulating Neuregulin-1 beta in Human Heart Failure. Circulation. 2009;119:E312–3.

18.•

Geisberg CA, Wang G, Safa RN, et al. Circulating neuregulin-1beta levels vary according to the angiographic severity of coronary artery disease and ischemia. Coron Artery Dis. 2011;22:577–82. This small retrospective observational cohort study discovered that plasma NRG-1 inversely correlated with severity of coronary artery disease and that NRG-1 was statisitcally higher in patients with stress tests that were positive for ischemia. The study has led to other work examining the role of NRG-1 as a biomarker of cardiovascular health.PubMedCentralPubMedCrossRef

19.

Chen B, Peng X, Pentassuglia L, Lim CC, Sawyer DB. Molecular and cellular mechanisms of anthracycline cardiotoxicity. Cardiovasc Toxicol. 2007;7:114–21.PubMedCrossRef

20.

De Angelis A, Piegari E, Cappetta D, et al. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation. 2010;121:276–92.PubMedCentralPubMedCrossRef

21.

Peng XY, Chen B, Lim CC, Sawyer DB. The cardiotoxicology of anthracycline chemotherapeutics: Translating molecular mechanism into preventative medicine. Mol Interv. 2005;5:163–71.PubMedCrossRef

22.

Fukazawa R, Miller TA, Kuramochi Y, et al. Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt. J Mol Cell Cardiol. 2003;35:1473–9.PubMedCrossRef

23.

Liu X, Gu X, Li Z, et al. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. J Am Coll Cardiol. 2006;48:1438–47.PubMedCrossRef

24.•

Jabbour A, Hayward CS, Keogh AM, et al. 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. 2011;13:83–92. This was a small single-arm phase I study investigating the safety, tolerability, and hemodynamic effect of a 12-hour infusion of recombinant NRG-1 in stable chronic heart failure patients. The study reveled that this form of recombinant NRG-1 was well-tolerated and produced favorable acute and chronic hemodynamic effects in patients with stable CHF.PubMedCrossRef

25.•

Gao R, Zhang J, Cheng L, et al. 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. 2010;55:1907–14. This study demonstrated that in a small randomized control trial of recombinant NRG-1 that a 12 hour infusion for 10-days slightly improved left ventricular ejection fraction and significantly improved ventricular volumes at 90-days suggesting that short-term treatment with rhNRG-1 results in a long-term reversal of remodeling.PubMedCrossRef

26.•

Lenihan D, Geisberg C, Caggiano A et al. Safety And Tolerability Of Glial Growth Factor 2 In Patients With Chronic Heart Failure: A Phase I Single Dose Escalation Study. JACC 2013;61. This was a phase I single-dose escalation study investigating the safety and tolerability of a 20-minute infusion of a different form of recombinant NRG-1 (Glial Growth Factor, GGF2). The study showed that this form of recombinant NRG-1 was safe and well-tolerated, and showed a trend toward improvement in ventricular ejection fraction at four weeks. Further development of GGF2 as a treatment for systolic heart failure is warranted

27.•

Geisberg CA, Abdallah WM, da Silva M, et al. This was a small prospective study of breast cancer patients who underwent serial measurement of cardiac function and biomarkers. More than 20% of women experienced cardiac dysfunction, detected by decline in LVEF, and were reclassified as stage B or C HF. Plasma NRG-1 levels were reduced after exposure to cardiotoxic chemotherapy, suggesting a loss in cardioprotective growth factor. Higher baseline NRG levels were observed in those with the greatest decline in LVEF, supporting the continued investigation of NRG as a potential prognostic marker in early-stage HF. J Card Fail. 2013;19:10–5.PubMedCentralPubMedCrossRef

28.

Pentassuglia L, Graf M, Lane H, et al. Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes. Exp Cell Res. 2009;315:1302–12.PubMedCrossRef

Titel: Neuregulin-1 Signaling in the Pathogenesis of Chemotherapy-Induced Heart Failure
verfasst von: Carrie Geisberg Lenneman
Publikationsdatum: 01.06.2014
Verlag: Springer US
Erschienen in: Current Heart Failure Reports / Ausgabe 2/2014
Print ISSN: 1546-9530
Elektronische ISSN: 1546-9549
DOI: https://doi.org/10.1007/s11897-014-0193-9

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