TY  - JOUR
T1  - Mechanistic Insights into Atrial Fibrillation in Dialysis Patients with End-Stage Renal Disease: The Roles of Rho Kinase Activity and Connexin 40
A1  - Domenico Prisa
A1  - Bianca Santo
A1  - Pamela D Moore
A1  - Anna Antonacci
JF  - Bulletin of Pioneering Researches of Medical and Clinical Science
JO  - Bull Pioneer Res Med Clin Sci
SN  - 3006-2659
Y1  - 2022
VL  - 1
IS  - 1
DO  - 10.51847/WASt5SnpzT
SP  - 24
EP  - 31
N2  - The underlying cellular and molecular mechanisms that trigger atrial fibrillation (AF) remain poorly understood. Previous studies have identified increased Rho kinase (ROCK) expression and elevated phosphorylation of myosin-phosphatase-target subunit-1 (MYPT-1), a marker of ROCK activity, in AF patients. These changes are linked to higher levels of connexin 40 (Cx40), a gap junction protein critical for fast electrical signal propagation in the heart. AF is particularly common in dialysis patients, who also show increased MYPT-1 phosphorylation correlating with left ventricular (LV) hypertrophy. Considering ROCK’s known role in cardiovascular and renal remodeling, which may compromise intercellular electrical coupling and promote AF onset, we assessed MYPT-1 phosphorylation, Cx40 expression, and their interrelationship in dialysis patients with AF. Mononuclear cells from dialysis patients with AF (DPAFs), dialysis patients with normal sinus rhythm (DPs), and healthy controls (C) were analyzed using western blotting, and M-mode echocardiography measured LV mass and left atrial systolic volume. Phospho-MYPT-1 was markedly elevated in DPAFs compared to DPs and controls (1.57 ± 0.17 vs. 0.69 ± 0.04 vs. 0.51 ± 0.05, p < 0.0001), while DPs also showed higher levels than controls (p = 0.009). Similarly, Cx40 expression was highest in DPAFs (1.23 ± 0.12) relative to DPs (0.74 ± 0.03) and controls (0.69 ± 0.03, p < 0.0001). In DPAFs, phospho-MYPT-1 positively correlated with Cx40 expression (p < 0.001), left atrial volume (p = 0.013), and LV mass (p = 0.014). Treatment with the ROCK inhibitor fasudil reduced both MYPT-1 phosphorylation (p < 0.01) and Cx40 levels (p = 0.03). These results implicate ROCK signaling and Cx40 in the pathogenesis of AF in dialysis patients, suggesting that targeting the ROCK pathway could provide novel mechanistic insights and potential therapeutic avenues.
UR  - https://bprmcs.com/article/mechanistic-insights-into-atrial-fibrillation-in-dialysis-patients-with-end-stage-renal-disease-the-zsvzmlszyzc1cdm
ER  -