Snail1 is positively correlated with atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease

Abstract

The present study investigated the association between Snail1 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) and to determine the possible mechanism underlying this interrelation. A total of 19 patients were included in the current study and were divided into two groups: A sinus rhythm (SR) group (n=9) and an AF group (n=10). All patients underwent heart valve replacement surgery, during which ~200 mg right atrium tissue was obtained. Hematoxylin and eosin and Masson's trichrome-stained sections were used to evaluate the morphological changes of cardiomyocytes and the level of fibrosis. Immunohistochemistry was applied to observe the location and expression of Snail1. Reverse transcription-quantitative polymerase chain reaction was used to measure Snail1 mRNA levels. Western blotting was used to determine changes in the expression of Snail1, as well as in the expression of proteins involved in the Wnt pathway, including Wnt1, Wnt 3a, Wnt8a, Wnt5a and Wnt11. Compared with the SR group, expanded cardiomyocytes and higher collagen deposition was detected in the atrial tissue of the AF group. The expression of Snail1 mRNA and protein was significantly higher in the AF group than in the SR group (P<0.05). Additionally, the expression of Wnt1, 3a and 8a in the canonical Wnt signaling pathway, and Wnt5a and 11 in the noncanonical Wnt signaling pathway were significantly increased in the AF group. Furthermore, the phosphorylation level of glycogen synthase kinase 3β (GSK3β) and the levels of β-catenin and GSK3β were significantly increased in the AF group compared with the SR group (P<0.05). Snail1 may be involved in the development and maintenance of atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease and may be developed as a novel biomarker to evaluate myocardial fibrosis in the future. Additionally, the current study suggests that the Wnt signaling pathway may participate in the process of increased Snail1 expression and atrial fibrosis in patients with AF and RHD.

WNT signaling in atrial fibrillation

“…42 Mechanistically, AF-dependent atrial fibrosis has been linked to elevated atrial expression levels of Snail1 that were found to be associated with increased expression of canonical Wnt 1, Wnt3A, and Wnt8A and the non-canonical family members Wnt5A and Wnt11. 43 Adenoviral overexpression of miR-27b-3p in rats reduced the duration and incidence of induced AF episodes and, notably, this was accompanied by reduced atrial fibrosis and fibrotic gene expression and diminished phospho-β-catenin and Wnt3A levels. 44 A similar decrease in profibrotic gene expression and fibrosis could be observed in primary rat fibroblasts upon over-expression of DACT2, which in HL-1 cells also reduced the phosphorylation of β-catenin.…”

Signalling pathways implicated in the pathogenesis of rheumatic heart disease (Review)

“…The Wnt signalling pathway involves multiple signal molecule-mediated transduction pathways, and the activation of this pathway is observed in several cardiovascular pathologies ( 28 ). This study ( 27 ) extended the prevalence of the Wnt signalling pathway in cardiovascular disease to RHD and highlighted Snail1. The Wnt signalling pathway and Snail1 are implicated in the EMT process.…”

“…Wnt signalling pathway and RHD. Guo et al (27) found that the Wnt signalling pathway increased the expression of Snail1 and participated in the process of RHD-induced atrial fibrosis. The method they used was similar to the three studies on MAPK mentioned above, i.e., comparison of the SR and AF groups of patients with RHD.…”

Insight on the Genetics of Atrial Fibrillation in Puerto Rican Hispanics

“…Secondly, the rs 2040862, nearest to the WNT8a gene, was associated with AF in our PRH cohort. WNT8a is part of the Wnt signaling pathway, and its expression is linked to increased collagen deposition and fibrosis around atrial cardiomyocytes, which is essential for providing a substrate for AF to develop [ 30 ]. Table 6 organizes each relevant SNP and the closest gene of association.…”