Renin-anglotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation
Renin-anglotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation
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DOI：
10.1097/hjh.0b013e3282f34a4a
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
Lin, Jiunn-Lee
中科院分区：
文献类型：
--
作者：
Tsai, Chia-Ti;Lai, Ling-Ping;Lin, Jiunn-Lee
目的心房颤动(房颤)患者心房局部组织血管紧张素II(AngII)水平升高，但其机制尚不清楚。我们假设心房肌细胞表达肾素-血管紧张素系统(RAS)的所有成分，并研究快速去极化是否足以通过上调RAS成分的表达来增加旁分泌Angii的产生。方法在HL-1心房细胞系中，以1.0V/cm和600/min(10 Hz)的快速场电刺激(RES)诱导HL-1细胞的快速去极化。结果在心房肌细胞中，Res诱导细胞内钙离子浓度持续升高，血管紧张素转换酶(ACE)、糜酶和血管紧张素原表达上调，导致血管紧张素Ⅱ的生成增加。依那普利[血管紧张素转换酶抑制剂(ACEI)]和糜抑素(糜酶抑制剂)可减弱RES诱导的血管紧张素Ⅱ的生成。Res刺激的心房肌细胞的条件培养液增加了心房肌细胞的[H-3]亮氨酸摄取和心钠素的表达，增加了心房成纤维细胞的[~3H]Pro摄取和I型胶原α1的表达。两者均通过与血管紧张素转换酶1型受体阻滞剂(ARB)共同孵育而减弱。结论心房肌细胞表达所有RAS组分，仅快速去极化就足以上调RAS组分，增加旁分泌血管紧张素Ⅱ的生成，并诱导心房结构改变，而ACEI、ARB和糜酶抑制剂可减弱这一作用。
Objectives Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression.Methods In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison.Results In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [H-3]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [3H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs.Conclusions Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.