Endothelin 1 regulates SOCC/TGF-βand involved in atrial fibrosis in rats with atrial fibrillation
10.19405/j.cnki.issn1000-1492.2024.03.010
- Author:
Zhuoran Jia
1
;
Manyu Dai
1
;
Shichu Liang
2
;
Jian Wu
1
;
Yangcheng Xue
1
;
Dingxin Zhang
1
;
Bing Shen
3
;
Ren Zhao
1
Author Information
1. Dept of Cardiology , The First Afiliated Hospital of Anhui Medical University , Hefei 230022
2. Dept of Cardiology , West China Hospital , Sichuan University , Chengdu 610041
3. Dept of Physiology , School of Basic Medical Science , Anhui Medical University , Hefei 230032
- Publication Type:Journal Article
- Keywords:
endothelin-1;
atrial fibrillation;
atrial fibrosis;
Orai1;
STIM1;
TGF-β;
HL-1 cell
- From:
Acta Universitatis Medicinalis Anhui
2024;59(3):429-435
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the effect and mechanism of endothelin-1 (ET-1) on atrial fibrosis in Atrial fibrillation (AF) rats .
Methods : Fourteen adult male SD rats were randomly divided into normal control ( NC) group and Atrial fibrillation (AF) group . The rat model of Atrial fibrillation was established by inj ecting 0.1 ml/ 100g CaCl2 Ach mixture into the tail vein once a day for one week . The control group was inj ected with the same dose of normal saline . An electrocardiogram of normal or atrial fibrillation was recorded on the first day and the eighth day in each group , and echocardiography was used to monitor atrial size and cardiac function . The fibrosis of atrial was ob served using Masson and HE staining. The expression of endothelin-1 ( ET-1) , collagen-I ( Col-I) , transforming growth factor-β(TGF-β) and the store operated calcium channel (SOCC) protein Orai1 , stromal in teraction molecule 1 (STIM1) in atrial tissue were detected by Western blot. HL-1 cells were cultured and treated with gradient concentration of ET-1 for 24 hours . Western blot was used to ob serve changes in the expression of TGF-β, Orai1 and STIM1 proteins in ET-1 /SOCC/TGF βsignaling pathway of HL-1 cells . Small interfering RNA ( siRNA) transfection method was used to knock down the expression of Orai1 in HL-1 cells , then the cells were treated with appropriate concentrations of ET-1 for 24 hours , and the expression of TGF-β protein in HL-1 cells was detected by Western blot.
Results :Compared with the control group , echocardiography showed a significant in crease in left atrial diameter (LAD) of the heart in atrial fibrillation rats (P < 0.05) . The HE and Masson staining results showed significant fibrosis in the myocardial tissue of AF group rats (P < 0.05) , and the Western blot re sults indicated the expression of ET-1 , Orai1 , STIM1 , TGF-β and COL-Ⅰ in the myocardial tissue of AF group significantly increased compared to the NC group (P < 0.05) . After ET 1 treatment of HL-1 cells , the protein ex pression of Orai1 , STIM1 and TGF βincreased (P < 0.05) , while knocking down Orai1 in HL-1 cells , ET-1 treat ment no longer caused the expression of TGF-β a significant upregulation .
Conclusion :AF caused by atrial fibril lation results in a significant increase in ET-1 expression in atrial tissue , and ET-1 /SOCC/TGF-β signal pathway promotes atrial fibrillation and fibrosis .
- Full text:2024062611303934835内皮素-1调控SOCC_T...参与房颤大鼠发生心房纤维化_贾卓然.pdf
