Yue Hui Zhang1, Qing Qing Hao2, Xiao Yu Wang3, Xu Chen3, Nan Wang3, Li Zhu3, Shu Ying Li3, Qing Tao Yu3, Bo Dong4. 1. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China Department of critical care Medicine, the Affiliated baoan Hospital of Nanfang Medical University, Shenzhen. 2. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China Departmentof Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China. 3. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. 4. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China Department of critical care Medicine, the Affiliated baoan Hospital of Nanfang Medical University, Shenzhen Departmentof Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China dongbo1@medmail.com.cn.
Abstract
INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. METHODS: Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. RESULTS: Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. CONCLUSIONS: The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway.
INTRODUCTION:Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. METHODS:Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. RESULTS:Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. CONCLUSIONS: The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway.
Authors: Fernanda B Fusco; Diego J Gomes; Kely C S Bispo; Veronica P Toledo; Denise F Barbeiro; Vera L Capelozzi; Luzia N S Furukawa; Ana P P Velosa; Walcy R Teodoro; Joel C Heimann; Eder C R Quintao; Marisa Passarelli; Edna R Nakandakare; Sergio Catanozi Journal: PLoS One Date: 2017-05-08 Impact factor: 3.240
Authors: Anastasia V Poznyak; Evgeny E Bezsonov; Ali H Eid; Tatyana V Popkova; Ludmila V Nedosugova; Antonina V Starodubova; Alexander N Orekhov Journal: Int J Mol Sci Date: 2021-04-29 Impact factor: 5.923
Authors: Anastasia V Poznyak; Dwaipayan Bharadwaj; Gauri Prasad; Andrey V Grechko; Margarita A Sazonova; Alexander N Orekhov Journal: Int J Mol Sci Date: 2021-06-22 Impact factor: 5.923
Authors: Hajira Dambha-Miller; Ali Albasri; Sam Hodgson; Christopher R Wilcox; Shareen Khan; Nazrul Islam; Paul Little; Simon J Griffin Journal: BMJ Open Date: 2020-09-14 Impact factor: 2.692