Histological and Biochemical Comparisons between Right Atrium and Left Atrium in Patients with Mitral Valvular Atrial Fibrillation

Background and Objectives: It has been known that the dominant driver of atrial fibrillation (AF) exists in the left atrium (LA) and the incidence of systemic thromboembolism is higher than that of pulmonary thromboembolism in patients with AF. Therefore, we hypothesized that histological and biochemical characteristics of the LA and the right atrium (RA) are different in patients with mitral valvular AF. Subjects and Methods: We analyzed the histology and messenger ribonucleic acid (mRNA) or protein expression associated with endothelial function and thrombogenesis in 33 human atrial appendage tissues (20 LA tissues, 13 RA tissues) taken from 25 patients {$57.7{\pm}11.3$ years old, 44% males, AF: sinus rhythm (SR)=17:8} with mitral valve disease. We also performed whole mRNA quantification in 8 tissues (both LA and RA tissues from 4 patients) by using next generation sequencing (NGS). Results: 1) The degree of fibrosis (p=0.001) and subendocardial smooth muscle thickness (p=0.004) were significantly greater in the LA than in the RA. 2) More advanced matrix fibrosis was found in the LA of patients with AF than in the LA of patients with SR (p=0.046), but not in the RA. 3) There was no LA-RA difference in protein (Western blot) and mRNA {quantitative real-time polymerase chain reaction (qRT-PCR)} expressions of $NF-{\kappa}B$, 3-NT, CD31, E-selectin, inducible NO synthase, stromal cell-derived $factor-1{\alpha}$, Endothelin-1, platelet-derived growth factor, myeloperoxidase, or NCX, except for higher mRNA expression of HCN4 in the RA (qRT-PCR, p=0.026) and that of KCNN1 in the LA (NGS, p=0.016). Conclusion: More advanced matrix and subendocardial remodeling were noticed in the LA than in the RA in patients with mitral valvular AF. However, the expressions of tissue factors associated with thrombogenesis were not significantly different between the RA and the LA.