Depletion of dendritic cells in perivascular adipose tissue improves arterial relaxation responses in type 2 diabetic mice.
Depletion of dendritic cells in perivascular adipose tissue improves arterial relaxation responses in type 2 diabetic mice.
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DOI：
10.1016/j.metabol.2018.03.002
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Hill MA
中科院分区：
文献类型：
--
作者：
Qiu T;Li M;Tanner MA;Yang Y;Sowers JR;Korthuis RJ;Hill MA
血管周围脂肪组织 (PVAT) 中多种亚型免疫细胞的积累被认为会导致 2 型糖尿病 (T2DM) 的血管炎症和功能障碍。本研究旨在探讨 PVAT 中树突状细胞在 T2DM 血管炎症发展和 PVAT 介导的血管舒张受损中的具体作用。研究使用 db/db 小鼠（T2DM 模型）及其 Db 杂合子 (DbHET)、瘦小鼠和血糖正常对照进行。通过将 DbHet 与 Flt3l−/−（FMS 激酶酪氨酸激酶配体无效）小鼠杂交来进行树突细胞去除。使用 PCR，发现大多数树突状细胞 (CD11c+) 位于 PVAT 中而不是血管壁中。流式细胞术同样显示，与 DbHET 对照相比，db/db 小鼠的脂肪组织中树突状细胞积累更多。与 DbHET 小鼠相比，db/db 小鼠的脂肪组织显示促炎细胞因子 TNF-α 和 IL-6 的 mRNA 水平升高，而抗炎介质脂联素的 mRNA 水平降低。 dbFlt3l-/dbFlt3l-中树突状细胞的消耗（通过流式细胞术证实）降低了糖尿病脂肪组织中的TNF-α和IL-6 mRNA水平，而不影响脂肪连接表达。此外，在肠系膜动脉中，树突状细胞耗竭提高了PVAT增强乙酰胆碱诱导的血管舒张和抗收缩活性的能力。在 T2DM 小鼠模型中，树突状细胞主要积聚在 PVAT 中，而不是血管壁本身。 PVAT 中树突状细胞的积累与促炎细胞因子的过量产生有关，这导致 PVAT 在 T2DM 中增强血管舒张和发挥抗收缩活性的能力受损。
Accumulation of multiple subtypes of immune cells in perivascular adipose tissue (PVAT) has been proposed to cause vascular inflammation and dysfunction in type 2 diabetes (T2DM). This study was designed to investigate specific roles for dendritic cells in PVAT in the development of vascular inflammation and impaired PVAT-mediated vasorelaxation in T2DM. Studies were performed using db/db mice (model of T2DM) and their Db heterozygote (DbHET), lean and normoglycemic controls. Dendritic cell depletion was performed by cross-breeding DbHet with Flt3l−/− (null for ligand for FMS-kinase tyrosine kinase) mice. Using PCR, it was found that the majority of dendritic cells (CD11c+) were located in PVAT rather than the vascular wall. Flow cytometry similarly showed greater dendritic cell accumulation in adipose tissue from db/db mice than DbHET controls. Adipose tissue from db/db mice displayed increased mRNA levels of proinflammatory cytokines TNF-α and IL-6 and decreased mRNA levels of the anti-inflammatory mediator adiponectin, compared to DbHET mice. Depletion of dendritic cells in dbFlt3l−/dbFlt3l− (confirmed by flow cytometry) reduced TNF-α and IL-6 mRNA levels in diabetic adipose tissue without influencing adiponection expression. Moreover, in mesenteric arteries, dendritic cell depletion improved the ability of PVAT to augment acetylcholine-induced vasorelaxation and anti-contractile activity. In a murine model of T2DM, dendritic cells accumulated predominantly in PVAT, as opposed to the vessel wall, per se. Accumulation of dendritic cells in PVAT was associated with overproduction of pro-inflammatory cytokines, which contributed to an impaired ability of PVAT to augment vasorelaxation and exert anti-contractile activity in T2DM.
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影响因子：
3.8
作者：
Huh JY;Park YJ;Ham M;Kim JB
通讯作者：
Kim JB
影响因子：
9.6
作者：
Doughty, L;Carcillo, JA;Janosky, J
通讯作者：
Janosky, J
DOI：
10.1161/atvbaha.114.303029
发表时间：
2014-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Brown NK;Zhou Z;Zhang J;Zeng R;Wu J;Eitzman DT;Chen YE;Chang L
通讯作者：
Chang L
DOI：
10.1007/978-1-62703-523-1_15
发表时间：
2013
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Grant, Ryan;Youm, Yun-Hee;Ravussin, Anthony;Dixit, Vishwa Deep
通讯作者：
Dixit, Vishwa Deep
影响因子：
2.8
作者：
Fernández-Alfonso MS;Gil-Ortega M;García-Prieto CF;Aranguez I;Ruiz-Gayo M;Somoza B
通讯作者：
Somoza B