title: ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.
abstract: BACKGROUND
  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: 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.
authors: Yue Hui
authors: YH
authors: Zhang
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China Departmentof Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Qing Qing
authors: QQ
authors: Hao
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Xiao Yu
authors: XY
authors: Wang
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Xu
authors: X
authors: Chen
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Nan
authors: N
authors: Wang
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Li
authors: L
authors: Zhu
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Shu Ying
authors: SY
authors: Li
authors: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Qing Tao
authors: QT
authors: Yu
authors: 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.
authors: Bo
authors: B
authors: Dong
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; D048049:Extracellular Signal-Regulated MAP Kinases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D019808:Losartan
keywords: Ang-(1-7); Atherosclerotic plaque; angiotensin-converting enzyme 2; losartan; signaling pathway