Galectin-3 in Atrial Fibrillation: Mechanisms and Therapeutic Implications

Abstract

Maintenance of atrial fibrillation is a complex mechanism, including extensive electrical and structural remodeling of the atria which involves progressive fibrogenesis. Galectin-3 is a biomarker of fibrosis, and, thus, may be involved in atrial remodeling in atrial fibrillation patients. We review the role of galectin-3 in AF mechanisms and its potential therapeutic implications.

Keywords: ablation; atrial fibrillation; galectin-3.

Figure 1

Three-dimensional voltage map of the left atrium obtained during invasive electrophysiological mapping (anterior view). The amplitude of local electrical activity is color-coded: from grey for low voltage areas to mauve for high voltage areas. Local amplitude correlates to the underlying atrial myocardial thickness, so that fibrotic areas translate into low voltage heterogeneous (“patchy”) anisotropic areas, here localized on the inter-atrial septum and the anterior wall.

Figure 2

Structure of Galectin-3. (A) Galectin-3 protein structure consists of N terminal Domain (NTD), which has a N terminal Region of 12 amino acids (aa) and contains serine 6 (S) phosphorylation site. The carbohydrate recognition domain (CRD) 130 aa comprise the C-terminal and contains the NWGR motif; (B) Pentameric structure of Galectin-3.

Figure 3

“Atrial fibrillation begets atrial fibrillation”. Galectin-3 production, promoted by atrial remodeling in atrial fibrillation patients, induces extracellular matrix production, mainly through the TGF-β/SMAD signaling pathway. Atrial fibrosis in return is associated with atrial dilatation, tissue anisotropy with heterogeneous electrical properties, which in turn favor atrial fibrillation initiation and maintenance.