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论文题目: Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension
英文论文题目: Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension
第一作者: Ruan, CC; Ma, Y; Ge, Q; Li, Y; Zhu, LM; Zhang, Y; Kong, LR; Wu, QH; Li, FH; Cheng, LX; Zhao, AZ; Zhu, DL; Gao, PJ
英文第一作者: Ruan, CC; Ma, Y; Ge, Q; Li, Y; Zhu, LM; Zhang, Y; Kong, LR; Wu, QH; Li, FH; Cheng, LX; Zhao, AZ; Zhu, DL; Gao, PJ
联系作者: Gao, PJ (reprint author), Shanghai Jiao Tong Univ, Sch Med, Dept Hypertens, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China.
英文联系作者: Gao, PJ (reprint author), Shanghai Jiao Tong Univ, Sch Med, Dept Hypertens, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China.
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发表年度: 2017
卷: 31
期: 3
页码: 1120-+
摘要: 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-alpha secretion from macrophages is required for inhibiting APN expression in adipocytes. Macrophage depletion reversed C5a agonist peptide-induced TNF-alpha 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.
英文摘要: 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-alpha secretion from macrophages is required for inhibiting APN expression in adipocytes. Macrophage depletion reversed C5a agonist peptide-induced TNF-alpha 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.
刊物名称: FASEB JOURNAL
英文刊物名称: FASEB JOURNAL
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学科: Biochemistry & Molecular Biology; Biology; Cell Biology
英文学科: Biochemistry & Molecular Biology; Biology; Cell Biology
影响因子: 5.498
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论文类别: Article
英文论文类别: Article
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