title: Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.
abstract: Perivascular adipose tissue (PVAT)-derived adiponectin (APN) is a secreted adipokine that protects against hypertension-related cardiovascular injury. However, the regulation of APN expression in hypertension remains to be explored. In this study, we demonstrated that down-regulation of APN was associated with complement activation in the PVAT of desoxycorticosterone acetate (DOCA)-salt hypertensive mice. Complement 3-deficient hypertensive mice were protected from ANP decrease in the PVAT. APN deficiency blockaded the protective effects of complement inhibition against hypertensive vascular injury. Mechanistically, complement 5a (C5a)-induced TNF-α secretion from macrophages is required for inhibiting APN expression in adipocytes. Macrophage depletion reversed C5a agonist peptide-induced TNF-α up-regulation and APN down-regulation in the PVAT of DOCA mice. Moreover, we detected increased macrophage infiltration and C5a expression associated with decreased APN expression in adipose tissue from patients with aldosterone-producing adenoma. These results identify a novel interaction between macrophages and adipocytes in the PVAT, where complement-mediated inhibition of APN acts as a potential risk factor for hypertensive vascular inflammation.-Ruan, C.-C., Ma, Y., Ge, Q., Li, Y., Zhu, L.-M., Zhang, Y., Kong, L.-R., Wu, Q-H., Li, F., Cheng, L., Zhao, A. Z., Zhu, D.-L., Gao, P.-J. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.
authors.affiliation: State Key Laboratory of Medical Genomics, gaopingjin@sibs.ac.cn.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Cheng-Chao
authors.initials: CC
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Medical Genomics, gaopingjin@sibs.ac.cn.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Genomics.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Department of Cardiology, Ruijin Hospital-Luwan Branch, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genomics.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genomics.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ling-Ran
authors.initials: LR
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Medical Genomics.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Wu
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, China.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Li
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Cheng
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, China.
authors.forename: Allan Z
authors.initials: AZ
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Genomics.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ding-Liang
authors.initials: DL
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genomics, gaopingjin@sibs.ac.cn.|Shanghai Key Laboratory of Hypertension, Ruijin Hospital, and.|Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003176:Complement C3 / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: D052242:Adiponectin; D003176:Complement C3; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a
keywords: adipocyte; macrophage; perivascular adipose tissue