title: Inactivation of Semicarbazide-Sensitive Amine Oxidase Stabilizes the Established Atherosclerotic Lesions via Inducing the Phenotypic Switch of Smooth Muscle Cells.
abstract: Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO) activity is associated with the severity of carotid atherosclerosis in clinic, the current study aims to investigate whether SSAO inactivation by semicarbazide is beneficial for established atherosclerotic lesions in LDLr knockout mice on a high-fat/high- cholesterol Western-type diet or after dietary lipid lowering. Despite no impact on plasma total cholesterol levels, the infiltration of circulating monocytes into peripheral tissues, and the size of atherosclerotic lesions, abrogation of SSAO activity resulted in the stabilization of established lesions as evidenced by the increased collagen contents under both conditions. Moreover, SSAO inactivation decreased Ly6Chigh monocytosis and lesion macrophage contents in hypercholesterolemic mice, while no effect was observed in mice after normalization of hypercholesterolemia by dietary lipid lowering. Strikingly, abrogation of SSAO activity significantly increased not only the absolute numbers of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic phenotype in established lesions of mice regardless of plasma cholesterol levels. Overall, our data indicate that SSAO inactivation in vivo stabilizes the established plaques mainly via inducing the switch of SMCs from a contractile to a synthetic phenotype. Targeting SSAO activity thus may represent a potential treatment for patients with atherosclerosis.
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Changzhou, Soochow University, Changzhou, 213003, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Soochow University, Suzhou, 215123, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Changzhou, Soochow University, Changzhou, 213003, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Niu
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Changzhou, Soochow University, Changzhou, 213003, China.
authors.forename: Mengya
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Changzhou, Soochow University, Changzhou, 213003, China.|Modern Medical Research Center, The First People's Hospital of Changzhou, Soochow University, Changzhou, 213003, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Soochow University, Suzhou, 215123, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D004041:Dietary Fats; D011973:Receptors, LDL; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse