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High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines

Author:
Li, Xin, Xue, Yu-Mei, Guo, Hui-Ming, Deng, Chun-Yu, Peng, De-Wei, Yang, Hui, Wei, Wei, Liu, Yang, Liu, Fang-Zhou, Wang, Zhao-Yu, Zhang, Meng-Zhen, Rao, Fang, Wu, Shu-Lin
Source:
Life sciences 2020 v.242 pp. 117209
ISSN:
0024-3205
Subject:
action potentials, animal disease models, appendages, atorvastatin, atrial fibrillation, calcium channels, high pressure treatment, hydrostatic pressure, hypertension, inflammation, patients, potassium, risk factors, tumor necrosis factor-alpha
Abstract:
Hypertension is an independent risk factor for atrial fibrillation (AF). However, the direct effect of hydrostatic pressure on atrial electrical remodeling is unclear. The present study investigated whether hydrostatic pressure is responsible for atrial electrical remodeling and addressed a potential role of inflammation in this pathology.Whole-cell patch-clamp recordings and biochemical assays were used to study the regulation and expression of ion channels in left atrial appendages in patients with AF, spontaneously hypertensive rats (SHRs), and atrium-derived cells (HL-1 cells) exposed to standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure.Both TNF-α and MIF were highly expressed in patients with AF and SHRs. AF inducibility in SHRs was higher after atrial burst pacing, accompanied by a decrease in the L-type calcium current (ICₐ,L), an increase in the transient outward K⁺ current (Iₜₒ) and ultra-rapid delayed rectifier K⁺ current (IKᵤᵣ), and a shortened action potential duration (APD), which could be inhibited by atorvastatin. Furthermore, exposure to elevated pressure was associated with electrical remodeling of the HL-1 cells. The peak current density of ICₐ,L was reduced, while Iₜₒ and IKᵤᵣ were increased. Moreover, the expression levels of Kv4.3, Kv1.5, TNF-α, and MIF were upregulated, while the expression of Cav1.2 was downregulated in HL-1 cells after treatment with high hydrostatic pressure (40 mmHg). Atorvastatin alleviated the electrical remodeling and increased inflammatory markers in HL-1 cells induced by high hydrostatic pressure.Elevated hydrostatic pressure led to atrial electrical remodeling and increased AF susceptibility by upregulating inflammation.
Agid:
6795738