[1]贾春森 李磊 李劲平 谭宏伟 周伟 聂永梅 于风旭.AngⅡ通过抑制人心房成纤维细胞BKCa通道诱导心房纤维化[J].心血管病学进展,2023,(11):1047.[doi:10.16806/j.cnki.issn.1004-3934.2023.11.020]
　JIA Chunsen,LI Lei,LI Jinping,et al.Ang Induces Atrial Fibrosis by Inhibiting BKCa Channel in Human Atrial Fibroblast[J].Advances in Cardiovascular Diseases,2023,(11):1047.[doi:10.16806/j.cnki.issn.1004-3934.2023.11.020]
点击复制

AngⅡ通过抑制人心房成纤维细胞BKCa通道诱导心房纤维化()
分享到：

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2023年11期
页码:
1047
栏目:
论著
出版日期:
2023-11-25

文章信息/Info

Title:
Ang Induces Atrial Fibrosis by Inhibiting BKCa Channel in Human Atrial Fibroblast
作者:
贾春森 李磊 李劲平 谭宏伟 周伟 聂永梅 于风旭
(西南医科大学附属医院心脏大血管外科,四川 泸州 646000)
Author(s):
JIA Chunsen; LI Lei;  LI Jinping; TAN Hongwei; ZHOU Wei; NIE Yongmei; YU Fengxu
(Department of Cardiovascular Surgery,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan,China )
关键词:
心房纤维化; 血管紧张素 Ⅱ; 人心房成纤维细胞; 大电导钙激活钾通道
Keywords:
Atrial fibrosis; Angiotensin Ⅱ; Human atrial fibroblast; Large conductance calcium-activated potassium channel
DOI:
10.16806/j.cnki.issn.1004-3934.2023.11.020
摘要:
目的 探讨在血管紧张素Ⅱ（AngⅡ）诱导心房纤维化的过程中，大电导钙激活钾通道（BKCa通道）的作用及机制。方法 通过组织块贴壁法获取原代人心房成纤维细胞，使用免疫荧光染色进行鉴定。用浓度为500 nmol/L 的AngⅡ处理人心房成纤维细胞24 h，实时荧光定量PCR与蛋白质印迹法用于检测处理前后纤维化标志基因α-SMA、CollagenⅠ和CollagenⅢ，以及BKCa通道 的α与β亚基的mRNA和蛋白表达水平，全细胞膜片钳技术检测Ang Ⅱ处理前后的BKCa通道的电流变化。结果 （1）人心房成纤维细胞经AngⅡ处理后，α-SMA、CollagenⅠ和CollagenⅢ的mRNA和蛋白表达水平升高；（2）经过AngⅡ处理后，BKCa通道α及β亚基mRNA和蛋白表达水平降低；（3）人心房成纤维细胞存在功能正常的BKCa通道，具有电压依赖性；（4）人心房成纤维细胞BKCa 通道的宏观电流幅度在经AngⅡ处理后降低；（5）在人心房成纤维细胞上过表达BKCa通道α亚基后，纤维化标志物α-SMA、CollagenⅠ和CollagenⅢ的表达受到了明显抑制。结论 AngⅡ可能通过抑制人成纤维细胞BKCa通道的表达和功能来诱导人心房成纤维细胞的纤维化，并最终导致心房纤维化。
Abstract:
Objective To investigate the mechanism of large conductance calcium-activated potassium channel (BKCa) in angiotensinⅡ (AngⅡ)-induced atrial fibrosis. Methods Primary human atrial fibroblasts were obtained by tissue block attachment method and identified by immunofluorescence staining. Human atrial fibroblasts were treated with Ang Ⅱ with concentration of 500 nmol /L for 24 h. Real-time fluorescent quantitative PCR and western blot were used to detect the mRNA and protein expression levels of fibrosis marker genes α-SMA,Collagen Ⅰ and Collagen III,as well as α and β subunits of BKCa channels before and after treatment. And whole cell patch clamp technique were used to detect the current changes of BKCa channels before and after AngⅡ treatment. Results (1) After Ang Ⅱ treatment of human atrial fibroblasts,the mRNA and protein expression levels of α-SMA, Collagen Ⅰ and Collagen Ⅲ increased;(2) After Ang Ⅱ treatment,the mRNA and protein expression of BKCa channel α and β subunits decreased;(3) Human atrial fibroblasts exist normal functioning BKCa channels, which are voltage dependent;(4) Macro current amplitude of BKCa channel in human atrial fibroblasts decreased after Ang Ⅱ treatment;(5) After overexpression of BKCa channel α subunit on human atrial fibroblasts,the mRNA and protein expression levels of fibrosis marker α-SMA,Collagen Ⅰ and Collagen Ⅲ decreased significantly. Conclusion AngⅡ may induce fibrosis in human atrial fibroblasts by inhibiting the expression and function of BKCa channels in human fibroblasts,and finally induce atrial fibrosis.

参考文献/References:

[1] Zimetbaum P. Atrial fibrillation[J]. Ann Intern Med,2017,166(5):ITC33-ITC48.
[2] Akhtar H,Al Sudani H,Hussein M,et al. Effects of renin-angiotensin-aldosterone system inhibition on left ventricular hypertrophy,diastolic function,and functional status in patients with hypertrophic cardiomyopathy:a systematic review[J]. Cureus,2022,14(7)：e26642.
[3] Koniari I,Artopoulou E,Mplani V,et al. Atrial fibrillation in heart failure patients:an update on renin-angiotensin-aldosterone system pathway blockade as a therapeutic and prevention target[J]. Cardiol J,2023,30(2):312-326.
[4] 周子默,周驰,杨雅元,等. 心肌纤维化的发病及治疗研究进展[J]. 湖北科技学院学报(医学版),2022,36(05):452-456.
[5] Wang X,Tu J,Jiang J,et al. Angiotensin Ⅱ type 2 receptor modulates synovial macrophage polarization by inhibiting GRK2 membrane translocation in a rat model of collagen-induced arthritis[J]. J Immunol,2020,205(11):3141-3153.
[6] Wen J,Li P,Cheng J,et al. Downregulation of AT2R decreases the responsiveness of BKCa channels to angiotensin Ⅱ in patients with hypertension[J]. J Mol Cell Cardiol,2019,131:20-28.
[7] Kampa RP,Flori L,S?k A,et al. Luteolin-induced activation of mitochondrial BKCa channels:undisclosed mechanism of cytoprotection[J]. Antioxidants(Basel),2022,11 (10):1892.
[8] Jo H,Bae EJ,Lee N,et al. Discovery and characterization of a potent activator of the BKCa channel that relives overactive bladder syndrome in rats[J]. Eur J Pharmacol,2022,927: 175055.
[9] Pavithra S,Kishor Kumar DG,Ramesh G,et al. Fat augments leptin-induced uterine contractions by decreasing JAK2 and BKCa channel expressions in late pregnant rats[J]. Cytokine,2022,157:155966.
[10] Wu Z,Yin W,Sun M,et al. BKCa mediates dysfunction in high glucose induced mesangial cell injury via TGF-β1/Smad2/3 signaling pathways[J]. Int J Endocrinol,2020,2020: 3260728.
[11] Szteyn,K,Singh H. BKCa channels as targets for cardioprotection[J]. Antioxidants(Basel),2020,9(8):760.
[12] Jakob D,Klesen A,Allegrini B,et al. Piezo1 and BKCa channels in human atrial fibroblasts:interplay and remodelling in atrial fibrillation[J]. J Mol Cell Cardiol,2021,158: 49-62.
[13] 陈瑞华,赵自刚,牛春雨,等.大鼠肺微血管内皮细胞的培养[J]. 中国微循环,2007,(01):16-19.
[14] Si Y,Wu Z,Gu L,et al. Changes of BKCA current and vascular reactivity in vascular smooth muscle of thoracic aorta and mesenteric artery in type 2 diabetic rats[J]. Pharmazie,2022,77(1):21-26.
[15] Li GR,Sun HY,Chen JB,et al. Characterization of multiple ion channels in cultured human cardiac fibroblasts[J]. PloS one,2009,4 (10),e7307.
[16] Wen JY,Zhang J,Chen S,et al. Endothelium-derived hydrogen sulfide acts as a hyperpolarizing factor and exerts neuroprotective effects via activation of large-conductance Ca2+-activated K+ channels[J]. Br J Pharmacol,2021,178(20):4155-4175.
[17] Naik JS,Walker BR. Endothelial-dependent dilation following chronic hypoxia involves TRPV4-mediated activation of endothelial BK channels[J]. Pflugers Arch,2018,470(4):633-648.
[18] Xie MJ,Ma YG,Gao F,et al. Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats[J]. Am J Physiol Cell Physiol,2010,298(6):C1489-C1500.
[19] Kim SE,Yin MZ,Kim HJ,et al. Decreased inward rectifier and voltage-gated K+ currents of the right septal coronary artery smooth muscle cells in pulmonary arterial hypertensive rats[J]. Korean J Physiol Pharmacol,2020,24(1):111-119.
[20] Gambade A,Zreika S,Guéguinou M,et al. Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells[J]. Oncotarget,2016,7(17):23785-23800.
[21] Schickling BM,England SK,Aykin-Burns N,et al. BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway[J]. Oncol Rep,2015,33(2):533-538.
[22] Roger S,Potier M,Vandier C,et al. Description and role in proliferation of iberiotoxin-sensitive currents in different human mammary epithelial normal and cancerous cells[J]. Biochim Biophys Acta,2004,1667(2):190-199.
[23] Sheng J,Shim W,Wei H,et al. Hydrogen sulphide suppresses human atrial fibroblast proliferation and transformation to myofibroblasts[J]. J Cell Mol Med,2013,17(10):1345-1354.

相似文献/References:

[1]吴亦融 徐健.心房颤动患者心房传导速度研究进展[J].心血管病学进展,2019,(9):1212.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.007]
　WU Yirong,XU Jian.Atrial Conduction Velocity in Patients with Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2019,(11):1212.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.007]
[2]张佳圩 黄从新.预防心房纤维化对心房颤动患者射频消融术后复发的影响[J].心血管病学进展,2020,(1):89.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.024]
　ZhANG Jiawei,HUANG Congxin.Prevention of Atrial Fibrosis Affects Atrial Fibrillation Recurrence after Radiofrequency Ablation[J].Advances in Cardiovascular Diseases,2020,(11):89.[doi:10.16806/j.cnki.issn.1004-3934.2020.01.024]
[3]王海星,尹德春,曲秀芬.病态窦房结综合征的心房纤维化血清学指标研究进展[J].心血管病学进展,2020,(3):310.[doi:10.16806/j.cnki. issn.1004-3934.2020.03.023]
　WANG Haixing,YIN Dechun,QU Xiufen.Serological Indicators of Atrial Fibrosis for Sick Sinus Syndrome[J].Advances in Cardiovascular Diseases,2020,(11):310.[doi:10.16806/j.cnki. issn.1004-3934.2020.03.023]

备注/Memo

备注/Memo:
收稿日期：2023-04-27基金项目:泸州市人民政府西南医科大学科技战略合作项目（2021LZXNYD-Z07,2021LZXNYD-J26）
更新日期/Last Update: 2023-12-13