The role of Toll-like receptor 2 and hypoxia-induced transcription factor-1α in the atrial structural remodeling of non-valvular atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. It is associated with an increased risk of ischemic stroke [ [1] Go A.S. Hylex E.M. Phillips K.A. et al. Prevalence of diagnosed a atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001; 285: 2370-2375 Crossref PubMed Scopus (5058) Google Scholar ]. A growing evidence suggests a possible association between inflammation and atrial fibrillation (AF) [ 2 Aviles R.J. Martin D.O. Apperson-Hansen C. et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003; 108: 3006-3010 Crossref PubMed Scopus (1118) Google Scholar , 3 Chung M.K. Martin D.O. Sprecher D. et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001; 104: 2886-2891 Crossref PubMed Scopus (1123) Google Scholar ]. Atrial biopsies of non-valvular AF patients also have provided the evidence that inflammation may participate in the pathogenesis of AF [ [4] Sekiguchi A. Yamashita T. Iwasaki Y. et al. Innate and adaptive immune reactions during progression of atrial fibrillation in humans. Jpn Circ J. 2008; 72: S514 Google Scholar ]. Recently, studies have demonstrated the changes in expression of gap junctions and activity of MMPs cause structural changes in the atrium that contribute to the pathogenesis of sustained AF. MMP-9 plays an important role in the degradation and remodeling of damaged tissues, including that of the heart [ 5 Polontchouk L. Haefliger J.A. Ebelt B. et al. Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria. J Am Coll Cardiol. 2001; 38: 883-891 Crossref PubMed Scopus (228) Google Scholar , 6 Arndt M. Lendeckel U. Röcken C. et al. Altered expression of ADAMs (a disintegrin and metalloproteinase) in fibrillating human atria. Circulation. 2002; 105: 720-725 Crossref PubMed Scopus (78) Google Scholar , 7 Nakano Y. Niida S. Dote K. et al. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation. J Am Coll Cardiol. 2004; 43: 818-825 Crossref PubMed Scopus (124) Google Scholar ]. However, the role of Toll-like receptor 2 (TLR2) and hypoxia-induced transcription factor-1α (HIF-1α) as immunological and inflammatory factor in atria structural remodeling of non-valvular AF has not been clarified [ 8 Pons J. Sauleda J. Regueiro V. et al. Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease. Respir Res. 2006; 7: 64 Crossref PubMed Scopus (68) Google Scholar , 9 Harter L. Mica L. Stocker R. et al. Increased expression of toll-like receptor-2 and -4 on leukocytes from patients with sepsis. Shock. 2004; 22: 403-409 Crossref PubMed Scopus (106) Google Scholar , 10 Thijssen V.L. van der Velden H.M. van Ankeren E.P. et al. Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovasc Res. 2002; 54: 427-437 Crossref PubMed Scopus (38) Google Scholar ].