title: Inactivation of semicarbazide-sensitive amine oxidase induces the phenotypic switch of smooth muscle cells and aggravates the development of atherosclerotic lesions.
abstract: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis.
  
  
  
  Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo.
  
  
  
  Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p = 0.0043) and advanced (1.8-fold, p = 0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ∼0.74-fold, p = 0.0002(early)/0.0016(advanced); SMC: ∼1.55-fold, p = 0.0003(early)/0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6C(high) monocytes (0.7-fold, p = 0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo.
  
  
  
  SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.
authors.affiliation: Department of Pathophysiology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhi
authors.affiliation: Department of Pathophysiology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Niu
authors.affiliation: Department of Pathophysiology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Mengya
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institutes of Biology & Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institutes of Biology & Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Institutes of Biology & Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institutes of Biology & Medical Sciences, Soochow University, Suzhou 215123, China. Electronic address: jwang79@suda.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China. Electronic address: yzhao@suda.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010641:Phenotype; D012663:Semicarbazides / Q000494:pharmacology*
chemical_list: D000950:Antigens, Ly; D004791:Enzyme Inhibitors; C494192:Ly-6C antigen, mouse; D012663:Semicarbazides; C010059:carbamylhydrazine; D002784:Cholesterol; D006631:Amine Oxidase (Copper-Containing)
keywords: Atherosclerosis; Phenotype switch; SSAO/VAP-1; Semicarbazide; VSMC