Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1).
Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1).
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急性肾损伤通过 FGFBP1（成纤维细胞生长因子结合蛋白 1）使脑血管系统对 Ang II（血管紧张素 II）收缩敏感
DOI：
10.1161/hypertensionaha.120.15582
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发表时间：
2020-12
期刊：
影响因子：
8.3
通讯作者：
Lai, En Yin
中科院分区：
文献类型：
--
作者：
Zhao, Liang;Cao, Xiaoyun;Li, Lingli;Wang, Xiaohua;Wang, Qin;Jiang, Shan;Tang, Chun;Zhou, Suhan;Xu, Nan;Cui, Yu;Hu, Weipeng;Fei, Lingyan;Zheng, Zhihua;Chen, Limeng;Schmidt, Marcel O.;Wei, Qichun;Zhao, Jingwei;Labes, Robert;Patzak, Andreas;Wilcox, Christopher S.;Fu, Xiaodong;Wellstein, Anton;Lai, En Yin
文本中提供了补充数字内容。急性肾损伤（AKI）导致多器官功能障碍。在这里，我们确定了 AKI 后导致脑血管损伤的可能机制。我们对C57Bl/6小鼠进行30分钟的双侧肾缺血再灌注损伤，并在24小时或1周后分离脑微血管和大血管，以测试其对血管收缩剂的反应，发现AKI后脑血管对Ang II（血管紧张素II）敏感。 AKI 后血清和肾组织中 FGF2（成纤维细胞生长因子 2）和 FGFBP1（FGF 结合蛋白 1）表达上调，提示可能与血管致敏有关。将 FGF2 和 FGFBP1 蛋白给予分离的健康脑血管模拟 AKI 后对 Ang II 的敏化。 Fgfbp1−/− AKI 小鼠的脑血管未能诱导 Ang II 致敏。与此互补的是，临床使用的 FGF 受体激酶抑制剂 BGJ398（Infigratinib）的全身治疗逆转了 AKI 诱导的脑血管对 Ang II 的敏感性。所有这些发现得出这样的结论：FGFBP1 对于 AKI 介导的脑血管对 Ang II 的敏感性尤其必要，FGFR 通路的抑制剂可能有益于预防 AKI 诱导的脑血管损伤。
Supplemental Digital Content is available in the text. Acute kidney injury (AKI) causes multiple organ dysfunction. Here, we identify a possible mechanism that can drive brain vessel injury after AKI. We induced 30-minute bilateral renal ischemia-reperfusion injury in C57Bl/6 mice and isolated brain microvessels and macrovessels 24 hours or 1 week later to test their responses to vasoconstrictors and found that after AKI brain vessels were sensitized to Ang II (angiotensin II). Upregulation of FGF2 (fibroblast growth factor 2) and FGFBP1 (FGF binding protein 1) expression in both serum and kidney tissue after AKI suggested a potential contribution to the vascular sensitization. Administration of FGF2 and FGFBP1 proteins to isolated healthy brain vessels mimicked the sensitization to Ang II after AKI. Brain vessels in Fgfbp1−/− AKI mice failed to induce Ang II sensitization. Complementary to this, systemic treatment with the clinically used FGF receptor kinase inhibitor BGJ398 (Infigratinib) reversed the AKI-induced brain vascular sensitization to Ang II. All these findings lead to the conclusion that FGFBP1 is especially necessary for AKI-mediated brain vascular sensitization to Ang II and inhibitors of FGFR pathway may be beneficial in preventing AKI-induced brain vessel injury.
影响因子：
10.8
作者：
Perry TE;Song M;Despres DJ;Kim SM;San H;Yu ZX;Raghavachari N;Schnermann J;Cannon RO 3rd;Orlic D
通讯作者：
Orlic D