Role of inflammation in the development of renal damage and dysfunction in angiotensin II-induced hypertension
Role of inflammation in the development of renal damage and dysfunction in angiotensin II-induced hypertension
复制标题
DOI：
10.1161/hypertensionaha.108.112706
复制
发表时间：
2008-08-01
期刊：
影响因子：
8.3
通讯作者：
Carretero, Oscar A.
中科院分区：
文献类型：
--
作者：
Liao, Tang-Dong;Yang, Xiao-Ping;Carretero, Oscar A.
血管紧张素II（Ang II）诱导的高血压与炎症反应有关，可能导致靶器官损伤的发展。我们验证了这样的假设，即在Ang II诱导的高血压中，CC趋化因子受体2（CCR 2）活化通过引起氧化应激、巨噬细胞浸润和细胞增殖在肾纤维化、损伤和功能障碍的发展中起重要作用。为了验证这一假设，我们使用CCR 2敲除小鼠（CCR 2（-/-））。CCR 2的天然配体是单核细胞趋化蛋白-1，一种对巨噬细胞募集和活化很重要的趋化因子。通过渗透性微型泵向CCR 2（-/-）和年龄匹配的野生型（CCR 2（-/-））C57 BL/6 J小鼠连续输注Ang II（5.2 ng/ 10 g/min）或载体2或4周。血管紧张素II输注引起相似的增加收缩压和左心室肥大的两种品系的小鼠。然而，在具有Ang II诱导的高血压的CCR 2（-/-）小鼠中，氧化应激、巨噬细胞浸润、蛋白尿和肾损伤显著减少，并且肾小球滤过率显著高于CCR 2（-/-）小鼠。我们的结论是，在血管紧张素II诱导的高血压中，CCR 2激活通过增加氧化应激和炎症在高血压肾病的发展中起重要作用。
Angiotensin II (Ang II)-induced hypertension is associated with an inflammatory response that may contribute to the development of target organ damage. We tested the hypothesis that, in Ang II -induced hypertension, CC chemokine receptor 2 (CCR2) activation plays an important role in the development of renal fibrosis, damage, and dysfunction by causing oxidative stress, macrophage infiltration, and cell proliferation. To test this hypothesis, we used CCR2 knockout mice ( CCR2 (-/-)). The natural ligand of CCR2 is monocyte chemoattractant protein-1, a chemokine important for macrophage recruitment and activation. CCR2(-/-) and age-matched wild-type ( CCR2(-/-)) C57BL/6J mice were infused continuously with either Ang II ( 5.2 ng/ 10 g per minute) or vehicle via osmotic minipumps for 2 or 4 weeks. Ang II infusion caused similar increases in systolic blood pressure and left ventricular hypertrophy in both strains of mice. However, in CCR2 (-/-) mice with Ang II - induced hypertension, oxidative stress, macrophage infiltration, albuminuria, and renal damage were significantly decreased, and glomerular filtration rate was significantly higher than in CCR2 (-/-) mice. We concluded that, in Ang II - induced hypertension, CCR2 activation plays an important role in the development of hypertensive nephropathy via increased oxidative stress and inflammation.