title: Cartilage oligomeric matrix protein prevents vascular aging and vascular smooth muscle cells senescence.
abstract: Aging-related vascular dysfunction contributes to cardiovascular morbidity and mortality. Cartilage oligomeric matrix protein (COMP), a vascular extracellular matrix protein, has been described as a negative regulatory factor for the vascular aging-related processes including atherosclerosis and vascular calcification. However, whether COMP is implicated in the process of vascular aging remains unclear. Here, we identified a novel function of COMP in preventing vascular aging and vascular smooth muscle cells (VSMCs) senescence. Firstly, vascular COMP expression was decreased in three different senescence-accelerated mouse models and was also declining with age. COMP(-/-) mice displayed elevated senescence-associated markers expression, including p53, p21 and p16, in the aortas compared with their wild type (WT) littermates. In accordance, COMP deficiency induced aging-related vascular dysfunction as evidenced by the significantly reduced phenylephrine-induced contraction and increased vascular stiffness as evaluated by pulse wave velocity. The aortic wall of COMP(-/-) mice was susceptible to senescence by displaying senescence-associated β-galactosidase (SA β-gal) activity induced by periadventitial application of CaCl2 to the abdominal aorta. In vitro, COMP knockdown by small interfering (si) RNA led to the elevation of p53, p21 and p16 as well as SA β-gal activity in VSMCs after H2O2 stimulation. VSMCs isolated from COMP(-/-) mice showed elevated senescence-associated markers expression and supplement of COMP adenovirus to COMP-deficient VSMCs greatly rescued cellular senescence. Taken together, these findings revealed the essential role of COMP in retarding the development of vascular aging and VSMC senescence.
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors: Meili
authors: M
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors: Yi
authors: Y
authors: Fu
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors: Cheng
authors: C
authors: Gao
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors: Yiting
authors: Y
authors: Jia
authors: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors: Yaqian
authors: Y
authors: Huang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Limei
authors: L
authors: Liu
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors: Xian
authors: X
authors: Wang
authors: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Wengong
authors: W
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China. Electronic address: kongw@bjmu.edu.cn.
authors: Wei
authors: W
authors: Kong
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism* / Q000503:physiopathology; D064236:Cartilage Oligomeric Matrix Protein / Q000172:deficiency / Q000378:metabolism*; D016922:Cellular Senescence; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D051381:Rats
chemical_list: D064236:Cartilage Oligomeric Matrix Protein
keywords: COMP; VSMC senescence; Vascular aging; Vascular extracellular matrix protein