T Regulatory Lymphocytes Prevent Aldosterone-Induced Vascular Injury
T Regulatory Lymphocytes Prevent Aldosterone-Induced Vascular Injury
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DOI：
10.1161/hypertensionaha.111.181123
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发表时间：
2012-02-01
期刊：
影响因子：
8.3
通讯作者：
Schiffrin, Ernesto L.
中科院分区：
文献类型：
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作者：
Kasal, Daniel A.;Barhoumi, Tlili;Schiffrin, Ernesto L.
醛固酮介导肾素-血管紧张素-醛固酮系统诱导高血压、氧化应激和血管炎症的作用。最近，我们发现血管紧张素II诱导的高血压和血管损伤至少部分是由巨噬细胞和T辅助效应淋巴细胞介导的。抑制性T调节淋巴细胞（Tlymphocytes，Tlymphocytes）的连续转移阻止了血管紧张素II的作用。我们假设Treg过继性转移会减弱醛固酮诱导的高血压和血管损伤。以1周的间隔静脉内注射3 × 105个CD 4（+）CD 25（+）细胞（代表Treg）或对照CD 4（+）CD 25（-）细胞，然后输注或不输注醛固酮（600 μ g/kg/天，SC）14天，同时接受1%盐水饮用。醛固酮引起血压小幅但持续升高（P < 0.001），降低血管舒张反应的乙酰胆碱66%（P < 0.001），两种培养基均增加：腔比阻力动脉中膜截面积减少60%（P < 0.001）使主动脉、肾脏和心脏的NADPH氧化酶活性增加2倍（P < 0.001），主动脉超氧化物生成量增加2倍（P < 0.05）。同时，醛固酮增加主动脉和肾皮质巨噬细胞浸润和主动脉T细胞浸润（均P < 0.05），并有减少肾皮质Treg的趋势。Treg过继转移阻止了醛固酮诱导的所有血管和肾脏效应。CD 4（+）CD 25（-）细胞的连续转移加重了醛固酮的作用，但内皮功能障碍和阻力动脉中膜/管腔比增加除外。因此，睾酮抑制醛固酮介导的血管损伤，部分通过对先天性和适应性免疫的影响，表明醛固酮诱导的血管损伤可以通过免疫调节方法预防。（高血压。2012; 59：324-330.）。在线补充资料
Aldosterone mediates actions of the renin-angiotensin-aldosterone system inducing hypertension, oxidative stress, and vascular inflammation. Recently, we showed that angiotensin II-induced hypertension and vascular damage are mediated at least in part by macrophages and T-helper effector lymphocytes. Adoptive transfer of suppressor T-regulatory lymphocytes (Tregs) prevented angiotensin II action. We hypothesized that Treg adoptive transfer would blunt aldosterone-induced hypertension and vascular damage. Thirteen to 15-week-old male C57BL/6 mice were injected intravenously at 1-week intervals with 3 x 10(5) CD4(+)CD25(+) cells (representing Treg) or control CD4(+)CD25(-) cells and then infused or not for 14 days with aldosterone (600 mu g/kg per day, SC) while receiving 1% saline to drink. Aldosterone induced a small but sustained increase in blood pressure (P < 0.001), decreased vasodilatory responses to acetylcholine by 66% (P < 0.001), increased both media: lumen ratio (P < 0.001) and media cross-sectional area of resistance arteries by 60% (P < 0.05), and increased NADPH oxidase activity 2-fold in aorta (P < 0.001), kidney and heart (P < 0.05), and aortic superoxide production. As well, aldosterone enhanced aortic and renal cortex macrophage infiltration and aortic T-cell infiltration (all P < 0.05), and tended to decrease Treg in the renal cortex. Treg adoptive transfer prevented all of the vascular and renal effects induced by aldosterone. Adoptive transfer of CD4(+)CD25(-) cells exacerbated aldosterone effects except endothelial dysfunction and increases in media: lumen ratio of resistance arteries. Thus, Tregs suppress aldosterone-mediated vascular injury, in part through effects on innate and adaptive immunity, suggesting that aldosterone-induced vascular damage could be prevented by an immunomodulatory approach. (Hypertension. 2012; 59: 324-330.). Online Data Supplement