Circulating serum levels of growth differentiation factor-15 and neuregulin-1 in patients with paroxysmal non-valvular atrial fibrillation

Growth differentiation factor-15 (GDF-15) is a stress-responsive member of the transforming growth factor-β superfamily that was originally cloned as a macrophage-inhibitory cytokine [ [1] Bootcov M.R. Bauskin A.R. Valenzuela S.M. et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci U S A. 1997; 94: 11514-11519 Crossref PubMed Scopus (927) Google Scholar ]. It rapidly increases following myocardial stretch, volume overload, oxidative stress and inflammatory state [ 2 Wollert K.C. Kempf T. Growth differentiation factor 15 in heart failure: an update. Curr Heart Fail Rep. 2012; 9: 337-345 Crossref PubMed Scopus (93) Google Scholar , 3 Lind L. Wallentin L. Kempf T. et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eur Heart J. 2009; 30: 2346-2353 Crossref PubMed Scopus (196) Google Scholar ]. In recent years, it is emerging as a novel biomarker to predict mortality and adverse events in patients with heart failure (HF) [ 4 Kempf T. von Haehling S. Peter T. et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol. 2007; 50: 1054-1060 Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar , 5 Foley P.W. Stegemann B. Ng K. et al. Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy. Eur Heart J. 2009; 30: 2749-2757 Crossref PubMed Scopus (47) Google Scholar , 6 Anand I.S. Kempf T. Rector T.S. et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the valsartan heart failure trial. Circulation. 2010; 122: 1387-1395 Crossref PubMed Scopus (251) Google Scholar , 7 Richter B. Koller L. Hohensinner P.J. et al. A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol. 2013; 168: 1251-1257 Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar ], acute coronary syndrome (ACS) [ 8 Khan S.Q. Ng K. Dhillon O. et al. Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J. 2009; 30: 1057-1065 Crossref PubMed Scopus (171) Google Scholar , 9 Eitel I. Blase P. Adams V. et al. Growth-differentiation factor 15 as predictor of mortality in acute reperfused ST-elevation myocardial infarction: insights from cardiovascular magnetic resonance. Heart. 2011; 97: 632-640 Crossref PubMed Scopus (53) Google Scholar , 10 Widera C. Pencina M.J. Meisner A. et al. Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome. Eur Heart J. 2012; 33: 1095-1104 Crossref PubMed Scopus (80) Google Scholar ] and acute pulmonary embolism [ [11] Lankeit M. Kempf T. Dellas C. et al. Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J Respir Crit Care Med. 2008; 177: 1018-1025 Crossref PubMed Scopus (151) Google Scholar ]. Neuregulin-1 (NRG-1) is a member of the epidermal growth factor (EGF) family [ [12] Mendes-Ferreira P. De Keulenaer G.W. Leite-Moreira A.F. Bras-Silva C. Therapeutic potential of neuregulin-1 in cardiovascular disease. Drug Discov Today. 2013; 18: 836-842 Crossref PubMed Scopus (50) Google Scholar ] and plays a critical role in cardiovascular development, cell survival, growth, and metabolism [ 13 Odiete O. Hill M.F. Sawyer D.B. Neuregulin in cardiovascular development and disease. Circ Res. 2012; 111: 1376-1385 Crossref PubMed Scopus (201) Google Scholar , 14 Pentassuglia L. Sawyer D.B. The role of Neuregulin-1beta/ErbB signaling in the heart. Exp Cell Res. 2009; 315: 627-637 Crossref PubMed Scopus (127) Google Scholar ]. Recently, NRG-1 was shown to be a stress-related cardiac growth and angiogenic biomarker [ 15 Moondra V. Sarma S. Buxton T. et al. Serum neuregulin-1beta as a biomarker of cardiovascular fitness. Open Biomark J. 2009; 2: 1-5 Crossref PubMed Scopus (20) Google Scholar , 16 Geisberg C.A. Wang G. Safa R.N. et al. Circulating neuregulin-1beta levels vary according to the angiographic severity of coronary artery disease and ischemia. Coron Artery Dis. 2011; 22: 577-582 Crossref PubMed Scopus (39) Google Scholar ].