Comparison of Ca2+, F4/80, and PARP-1/NF-κB Pathway Expression in Atrial Myocardium of Patients with Sinus Rhythm and Atrial Fibrillation in Rheumatic Heart Valve Disease

Abstract

Abstract Background：Atrial fibrillation (AF) is more likely in those with rheumatic valvular heart fisease (RHD). The role of atrial remodeling in the onset and progression of AF is critical. Objective: In this work, we examined the morphological changes and molecular biological variations in atrial tissue in rheumatic valvular heart disease patients with sinus rhythm, paroxysmal AF, and persistent AF respectively. Methods: Twelve patients with RHD who had prosthetic heart valve replacement were included in this study, with four in the sinus rhythm (SR) group, four in the paroxysmal atrial fibrillation (par-AF) group, and four in the persistent AF(per-AF) group. Before surgery, all of the patients had a transthoracic echocardiogram and the appropriate clinical data was obtained. The contents of Ca2+ and macrophage marker F4/80 in atrial myocardial tissue were measured by flow cytometry, and PARP-1/NF-κB was determined by PCR and Western blot, respectively. The morphological changes of atrial tissue were observed by HE and Masson staining, and the contents of Ca2+ and macrophage marker F4/80 in atrial myocardial tissue were measured by flow cytometry, and PARP-1/ PCR and Western blot were used to assess the expression of PARP-1/NF-κB pathway mRNA and protein in atrial myocardial tissues. Results: Compared with the SR patients, the left atrial internal diameter was not significantly enlarged in the AF patients (P > 0.05), but combined with more comorbidities and a higher degree of fibrosis; In the AF patients, there was a substantial rise in Ca2+ and F4/80-positive macrophage concentration in the left atrial tissue(P < 0.05); The expression of PARP-1/NF-κB pathway mRNA was considerably higher in the AF patients' left atrial tissue. In the AF groups, much more PARP-1/NF-B pathway protein was expressed than in the SR group; Furthermore, these variables differed significantly in both the paroxysmal and persistent AF groups (P < 0.05). Conclusion: Increased expression of the PARP-1/NF-κB pathway as well as elevated Ca2+ and F4/80-positive macrophage content in atrial myocardial tissue of RHD suggest that Ca2+-handling abnormalities, macrophage infiltration, and inflammatory activation may be involved in and mediate the atrial remodeling process in AF.