High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines
High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines
复制标题
高静水压通过炎症细胞因子的上调诱导心房电重塑。
DOI：
10.1016/j.lfs.2019.117209
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发表时间：
2020-02-01
期刊：
影响因子：
6.1
通讯作者：
Wu, Shu-Lin
中科院分区：
文献类型：
--
作者：
Li, Xin;Xue, Yu-Mei;Wu, Shu-Lin
目的：高血压是房颤（AF）的独立危险因素。然而，静水压对心房电重构的直接影响尚不清楚。本研究调查了静水压力是否是心房电重构的原因，并探讨了炎症在这种病理学中的潜在作用。主要方法：采用全细胞膜片钳技术和生化分析方法，研究了房颤患者、自发性高血压大鼠（SHR）、和心房源性细胞（HL-1细胞）暴露于标准（0 mmHg）和升高（20，40 mmHg）的流体静压。心房短阵起搏后，SHR的AF诱发率增高，伴有L型钙电流（I-Ca，I-L）降低，瞬时外向钾电流（I-to）和超快速延迟整流钾电流（I-Kur）增加，动作电位时程（APD）缩短，阿托伐他汀可抑制上述变化。此外，暴露于高压与电重构的HL-1细胞。I-Ca、I-L峰电流密度降低，I-to、I-Kur峰电流密度升高。此外，高静水压（40 mmHg）处理后，HL-1细胞中Kv4.3、Kv1.5、TNF-α和MIF的表达水平上调，而Cav1.2的表达下调。阿托伐他汀可减轻高静水压诱导的HL-1细胞电重构，并增加细胞内炎性标志物的含量。意义：高静水压通过上调炎症反应导致心房电重构，增加AF易感性。
Aims: 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.Main methods: 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.Key findings: Both TNF-alpha 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 (I-Ca,I-L), an increase in the transient outward K+ current (I-to) and ultra-rapid delayed rectifier K+ current (I-Kur), 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 I-Ca,I-L was reduced, while I-to and I-Kur were increased. Moreover, the expression levels of Kv4.3, Kv1.5, TNF-alpha, 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.Significance: Elevated hydrostatic pressure led to atrial electrical remodeling and increased AF susceptibility by upregulating inflammation.