Ya-Wen Hsiao1, Yung-Nan Tsai2, Yu-Ting Huang1, Shuen-Hsin Liu3, Yenn-Jiang Lin1,4, Li-Wei Lo1,4, Yu-Feng Hu1,4, Fa-Po Chung1,4, Shien-Fong Lin5, Shih-Lin Chang6,7, Satoshi Higa8, Shih-Ann Chen1,4. 1. Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201 Sec- 2, Shih-Pai Road, Taipei, Taiwan. 2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan. 4. Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. 5. Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan. 6. Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201 Sec- 2, Shih-Pai Road, Taipei, Taiwan. ep.slchang@msa.hinet.net. 7. Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. ep.slchang@msa.hinet.net. 8. Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa, Japan.
Abstract
PURPOSE: Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. METHODS: Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. RESULTS: After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. CONCLUSIONS: RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.
PURPOSE: Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. METHODS: Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. RESULTS: After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. CONCLUSIONS: RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.
Authors: Danesh Soltani; Bayan Azizi; Roja Rahimi; Azita H Talasaz; Hossein Rezaeizadeh; Ali Vasheghani-Farahani Journal: Front Cardiovasc Med Date: 2022-09-29