Macrophage Depletion Lowered Blood Pressure and Attenuated Hypertensive Renal Injury and Fibrosis.
Macrophage Depletion Lowered Blood Pressure and Attenuated Hypertensive Renal Injury and Fibrosis.
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巨噬细胞耗竭可降低血压并减轻高血压肾损伤和纤维化。
DOI：
10.3389/fphys.2018.00473
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发表时间：
2018
影响因子：
4
通讯作者：
Zhou MS
中科院分区：
文献类型：
--
作者：
Huang L;Wang A;Hao Y;Li W;Liu C;Yang Z;Zheng F;Zhou MS
单核/巨噬细胞募集与高血压肾损害程度密切相关。我们研究了在高血压肾损伤中，巨噬细胞使用脂质体包裹的氯膦酸盐(LEC)来消耗单核/巨噬细胞的直接作用。用加压剂量的血管紧张素Ⅱ(Ang，1.4 mg/kg/d)加LEC或PBS-脂质体治疗C57BL/6小鼠2周。Ang II小鼠出现高血压、蛋白尿、肾小球硬化和肾纤维化。LEC治疗可降低Ang II小鼠的收缩压(SBP)、蛋白尿，并对肾脏结构损伤具有保护作用。Ang II显著增加肾巨噬细胞(MOMA2+细胞)的浸润，增加肾肿瘤坏死因子α和白细胞介素1(ILβ1)的表达，但显著低于Ang II/L EC小鼠。Ang II可增加肾脏氧化应激，增加促纤维化因子转化生长因子、β1和纤维连接蛋白的表达。Ang II还抑制内皮型一氧化氮合酶的磷酸化[内皮型一氧化氮合酶(ENOS)，Ser1177]。LEC治疗降低了Ang II小鼠肾脏氧化应激和转化生长因子β1和纤维连接蛋白的表达，增加了磷酸化eNOS的表达。在盐敏感型高血压Dahl大鼠中，LEC治疗4周可显著减轻高盐摄入所致的SBP升高，并对肾脏损伤和纤维化具有保护作用。我们的结果表明，肾巨噬细胞在高血压和高血压肾损伤和纤维化的发生发展中起关键作用；其潜在的机制可能与减轻巨噬细胞驱动的肾脏炎症和恢复肾脏氧化应激和eNOS之间的平衡有关。因此，应考虑将巨噬细胞作为一个潜在的治疗靶点，以减少高血压肾病的不良后果。
Monocyte/macrophage recruitment is closely associated with the degree of hypertensive renal injury. We investigated the direct role of macrophages using liposome-encapsulated clodronate (LEC) to deplete monocytes/macrophages in hypertensive renal injury. C57BL/6 mice were treated with a pressor dose of angiotensin (Ang, 1.4 mg/kg/day) II plus LEC or the PBS-liposome for 2 weeks. Ang II mice developed hypertension, albuminuria, glomerulosclerosis, and renal fibrosis. LEC treatment reduced systolic blood pressure (SBP), albuminuria, and protected against renal structural injury in Ang II mice. Ang II significantly increased renal macrophage infiltration (MOMA2+ cells) and the expression of renal tumor necrosis factor α and interleukin β1, which were significantly reduced in Ang II/LEC mice. Ang II increased renal oxidative stress and the expression of profibrotic factors transforming growth factor (TGF) β1 and fibronectin. Ang II also inhibited the phosphorylation of endothelial nitric oxide synthase [phospho-endothelial nitric oxide synthesis (eNOS), ser1177]. LEC treatment reduced renal oxidative stress and TGFβ1 and fibronectin expressions, and increased phospho-eNOS expression in the Ang II mice. In Dahl rats of salt-sensitive hypertension, LEC treatment for 4 weeks significantly attenuated the elevation of SBP induced by high salt intake and protected against renal injury and fibrosis. Our results demonstrate that renal macrophages play a critical role in the development of hypertension and hypertensive renal injury and fibrosis; the underlying mechanisms may be involved in the reduction in macrophage-driven renal inflammation and restoration of the balance between renal oxidative stress and eNOS. Therefore, macrophages should be considered as a potential therapeutic target to reduce the adverse consequences of hypertensive renal diseases.
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DOI：
10.1056/nejmoa0910975
发表时间：
2010-09-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Appel LJ;Wright JT Jr;Greene T;Agodoa LY;Astor BC;Bakris GL;Cleveland WH;Charleston J;Contreras G;Faulkner ML;Gabbai FB;Gassman JJ;Hebert LA;Jamerson KA;Kopple JD;Kusek JW;Lash JP;Lea JP;Lewis JB;Lipkowitz MS;Massry SG;Miller ER;Norris K;Phillips RA;Pogue VA;Randall OS;Rostand SG;Smogorzewski MJ;Toto RD;Wang X;AASK Collaborative Research Group
通讯作者：
AASK Collaborative Research Group
影响因子：
8.3
作者：
Barhoumi, Tlili;Kasal, Daniel A.;Schiffrin, Ernesto L.
通讯作者：
Schiffrin, Ernesto L.
影响因子：
13.6
作者：
Lech, Maciej;Groebmayr, Regina;Anders, Hans-Joachim
通讯作者：
Anders, Hans-Joachim
影响因子：
15.9
作者：
Rajagopalan, S;Kurz, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
8.3
作者：
Liao, Tang-Dong;Yang, Xiao-Ping;Carretero, Oscar A.
通讯作者：
Carretero, Oscar A.