Class A scavenger receptor deficiency augments angiotensin II-induced vascular remodeling
Class A scavenger receptor deficiency augments angiotensin II-induced vascular remodeling
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A 类清道夫受体缺乏会增强血管紧张素 II 诱导的血管重塑
DOI：
10.1016/j.bcp.2014.05.015
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发表时间：
2014
影响因子：
5.8
通讯作者：
Chen Qi
中科院分区：
文献类型：
--
作者：
Qian Lingling;Li Xiaoyu;Fang Ru;Wang Zhuoyun;Xu Yiming;Zhang Hanwen;Bai Hui;Yang Qing;Zhu Xudong;Ben Jingjing;Xu Yong;Chen Qi
A类清道夫受体（SR-A）是参与巨噬细胞介导的炎症的多功能分子。在这里，我们评估了SR-A在血管紧张素II（Ang II）诱导的高血压血管重塑中的作用。慢性输注Ang II导致SR-A敲除（SR-A-/-）和野生型（SR-A+/+）小鼠的收缩压升高，这两组之间无显著差异。然而，与SR-A+/+高血压小鼠相比，SR-A−/−高血压小鼠的动脉壁增厚和血管细胞增殖明显增加。在SR-A−/−小鼠的血管组织中，M1巨噬细胞标志物增加，而M2巨噬细胞标志物减少。共培养实验表明，SR-A−/−腹腔巨噬细胞产生更多的促炎细胞因子如TNF-α，导致体外原代血管平滑肌细胞更强的增殖。此外，SR-A−/−巨噬细胞更倾向于脂多糖诱导的M1分化，而抵抗白细胞介素-4诱导的M2分化。重要的是，将SR-A−/−骨髓移植到SR-A+/+小鼠中显著增强了Ang II诱导的血管重塑。这些结果表明SR-A通过调节巨噬细胞极化对Ang II诱导的血管重塑至关重要。因此，SR-A可能是干预高血压血管重构的一个有用的治疗靶点。
Class A scavenger receptor (SR-A) is a multifunctional molecule that participates in macrophage-mediated inflammation. Here we evaluated the role of SR-A in angiotensin II (Ang II)-induced hypertensive vascular remodeling. Chronic infusion of Ang II leads to an increased systolic blood pressure both in SR-A knockout (SR-A−/−) and wild type (SR-A+/+) mice with no significant difference between these two groups. SR-A−/−hypertensive mice, however, exhibited a marked augmentation of arterial wall thickening and vascular cell proliferation compared with SR-A+/+hypertensive mice. M1 macrophage markers were increased whereas M2 macrophage markers were decreased in vascular tissues of SR-A−/−mice. Co-culture experiments revealed that more pro-inflammatory cytokines like TNF-α were produced by SR-A−/−peritoneal macrophages leading to a stronger proliferation of primary vascular smooth muscle cellsin vitro. In addition, SR-A−/−macrophages were more prone to lipopolysaccharide-induced M1 differentiation while resisting interleukin-4-induced M2 differentiation. Importantly, transplantation of SR-A−/−bone marrow into SR-A+/+mice significantly augmented Ang II-induced vascular remodeling. These results show that SR-A is critical for Ang II-induced vascular remodeling by regulating macrophage polarization. Therefore, SR-A may be a useful therapeutic target for the intervention of hypertensive vascular remodeling.