Yonghong Li1, Junjie Guo2, Haichu Yu2, Jingwei Zhou3, Xianming Chu2, Bo Hou2, Junhua Ge2, Tingting Li2, Shuo Duan2, Hui Xu2, Xi Yang2. 1. Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266003,China. Electronic address: li.yonghong@yandex.ru. 2. Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266003,China. 3. Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266003,China.
Abstract
PURPOSE: Restenosis is the main complication after percutaneous coronary intervention. The proliferation of new intima contributes to the process. In this study, we aimed to explore the effect of olmesartan on intimal thickening after balloon injury and possible mechanism. METHODS: Aortic endothelial denudation model was made by a 2F balloon catheter. Thirty-six rats were randomly allocated into three groups: Control (n = 12) Surgery (n = 12, received vascular balloon injury) and Olmesartan (n = 12, received 3 mg.kg-1.d-1olmesartan after injury). Fourteen and 28 days after injury, HE staining was used to assess the aortic endothelial injury. Radioimmunological method was used to examine the level of angiotensin II (Ang II). Western blotting and reverse transcription polymerse chain reaction (RT-PCR) were employed to detect the protein and mRNA level of Apelin/APJ. RESULTS: After vascular balloon injury, the proliferation of vascular smooth muscle cells and the intimal thickening were increased. The mRNA and protein level of Ang II, AT1, Apelin and APJ mRNA were promoted by vascular balloon injury. Olmesartan decreased the proliferation of vascular smooth muscle cells and the intimal thickening. Olmesartan decreased the expression of Ang II and AT1, but further increased the expression of Apelin and APJ. Balloon injury also induced the activation of Extracellular signal-regulated kinase (ERK) signaling and olmesartan decreased the effect. CONCLUSION: Olmesartan inhibits the intimal thickening through activating Apelin/APJ and inhibiting AngII-AT1 and ERK pathway.
PURPOSE: Restenosis is the main complication after percutaneous coronary intervention. The proliferation of new intima contributes to the process. In this study, we aimed to explore the effect of olmesartan on intimal thickening after balloon injury and possible mechanism. METHODS: Aortic endothelial denudation model was made by a 2F balloon catheter. Thirty-six rats were randomly allocated into three groups: Control (n = 12) Surgery (n = 12, received vascular balloon injury) and Olmesartan (n = 12, received 3 mg.kg-1.d-1olmesartan after injury). Fourteen and 28 days after injury, HE staining was used to assess the aortic endothelial injury. Radioimmunological method was used to examine the level of angiotensin II (Ang II). Western blotting and reverse transcription polymerse chain reaction (RT-PCR) were employed to detect the protein and mRNA level of Apelin/APJ. RESULTS: After vascular balloon injury, the proliferation of vascular smooth muscle cells and the intimal thickening were increased. The mRNA and protein level of Ang II, AT1, Apelin and APJ mRNA were promoted by vascular balloon injury. Olmesartan decreased the proliferation of vascular smooth muscle cells and the intimal thickening. Olmesartan decreased the expression of Ang II and AT1, but further increased the expression of Apelin and APJ. Balloon injury also induced the activation of Extracellular signal-regulated kinase (ERK) signaling and olmesartan decreased the effect. CONCLUSION:Olmesartan inhibits the intimal thickening through activating Apelin/APJ and inhibiting AngII-AT1 and ERK pathway.
Authors: Jochen Dutzmann; Lena Marie Bode; Katrin Kalies; Laura Korte; Kai Knöpp; Frederik Julius Kloss; Mirja Sirisko; Claudia Pilowski; Susanne Koch; Heiko Schenk; Jan-Marcus Daniel; Johann Bauersachs; Daniel G Sedding Journal: Front Cardiovasc Med Date: 2022-08-09