title: Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells.
abstract: The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next, autophagic activity was examined in AD mice model established by β-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD.
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Zhao
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Guan-Xin
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Su-Xuan
authors.initials: SX
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Song-Hua
authors.initials: SH
authors.lastname: Li
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Guo-Kun
authors.initials: GK
authors.lastname: Wang
authors.affiliation: Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China. Electronic address: dearwgk@163.com.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Xu
mesh_terms: D000629:Aminopropionitrile / Q000031:analogs & derivatives / Q000737:chemistry; D000784:Aortic Dissection / Q000473:pathology*; D000804:Angiotensin II / Q000737:chemistry; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004548:Elasticity; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010641:Phenotype; D015854:Up-Regulation
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D000804:Angiotensin II; C027243:beta-aminopropionitrile fumarate; D000629:Aminopropionitrile
keywords: Autophagy; Phenotype switch; Smooth muscle cells; Thoracic aortic dissection