Endothelial BBSome is essential for vascular, metabolic, and retinal functions.
Endothelial BBSome is essential for vascular, metabolic, and retinal functions.
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DOI：
10.1016/j.molmet.2021.101308
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发表时间：
2021-11
影响因子：
8.1
通讯作者：
Rahmouni K
中科院分区：
文献类型：
--
作者：
Jiang J;Reho JJ;Bhattarai S;Cherascu I;Hedberg-Buenz A;Meyer KJ;Tayyari F;Rauckhorst AJ;Guo DF;Morgan DA;Taylor EB;Anderson MG;Drack AV;Rahmouni K
排列在整个血管系统中的内皮细胞在控制包括新陈代谢在内的各种生理过程中发挥着关键作用。此外，内皮功能障碍与许多病理状况相关，包括肥胖。在这里，我们评估了 BBSome 的作用，BBSome 是内皮细胞中由八种 Bardet-Biedl 综合征 (BBS) 蛋白组成的蛋白复合物。我们研究了 BBSome 破坏内皮细胞对血管功能、体重、葡萄糖稳态以及肝脏和视网膜的影响。为此，我们通过 Bbs1 基因缺失培育了内皮细胞选择性 BBSome 破坏的小鼠。我们发现内皮细胞特异性 BBSome 破坏会导致内皮功能障碍，如主动脉和肠系膜动脉中乙酰胆碱诱导的血管舒张功能受损所示。这与肠系膜动脉中血栓素 A2 受体激动剂 (U46619) 的收缩反应增加有关。从机制上讲，我们证明内皮细胞中缺乏 Bbs1 基因的小鼠表现出血管血管紧张素原基因表达升高，这表明肾素-血管紧张素系统激活在内皮细胞 BBSome 缺陷引起的血管变化中。引人注目的是，我们的数据表明，内皮 BBSome 缺乏会增加体重和脂肪量，并导致肝脂肪变性，同时改变脂质代谢相关基因和代谢组学特征的肝脏表达。此外，视网膜电图和光学相干断层扫描分析显示视网膜功能和结构异常，这是由内皮 BBSome 缺失引起的。我们的研究结果表明，内皮细胞中的 BBSome 是调节血管功能、肥胖、肝脂质代谢和视网膜功能所必需的。内皮细胞中 BBSome 的破坏会改变血管反应性。内皮细胞中 BBSome 的缺失会增加血管血管紧张素原基因的表达。内皮BBSome缺乏会增加体重和脂肪量并导致肝脂肪变性。内皮 BBSome 的缺失会导致视网膜功能和结构异常。
Endothelial cells that line the entire vascular system play a pivotal role in the control of various physiological processes, including metabolism. Additionally, endothelial dysfunction is associated with many pathological conditions, including obesity. Here, we assessed the role of the BBSome, a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins in endothelial cells. We studied the effects of BBSome disruption in endothelial cells on vascular function, body weight, glucose homeostasis, and the liver and retina. For this, we generated mice with selective BBSome disruption in endothelial cells through Bbs1 gene deletion. We found that endothelial cell–specific BBSome disruption causes endothelial dysfunction, as indicated by the impaired acetylcholine-induced vasorelaxation in both the aorta and mesenteric artery. This was associated with an increase in the contractile response to thromboxane A2 receptor agonist (U46619) in the mesenteric artery. Mechanistically, we demonstrated that mice lacking the Bbs1 gene in endothelial cells show elevated vascular angiotensinogen gene expression, implicating renin-angiotensin system activation in the vascular changes evoked by endothelial BBSome deficiency. Strikingly, our data indicate that endothelial BBSome deficiency increases body weight and fat mass and causes hepatosteatosis along with alterations in hepatic expression of lipid metabolism–related genes and metabolomics profile. In addition, electroretinogram and optical coherence tomography analyses revealed functional and structural abnormalities in the retina, evoked by absence of the endothelial BBSome. Our findings demonstrate that the BBSome in endothelial cells is required for the regulation of vascular function, adiposity, hepatic lipid metabolism, and retinal function. Disruption of the BBSome in endothelial cells alters vascular reactivity. Loss of the BBSome in endothelial cells increases vascular angiotensinogen gene expression. Endothelial BBSome deficiency increases body weight and fat mass and causes hepatosteatosis. Absence of the endothelial BBSome induces functional and structural abnormalities in the retina.
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影响因子：
20.1
作者：
Pi X;Xie L;Patterson C
通讯作者：
Patterson C
DOI：
10.1073/pnas.0402354101
发表时间：
2004-06-08
影响因子：
11.1
作者：
Mykytyn, K;Mullins, RF;Sheffield, VC
通讯作者：
Sheffield, VC
影响因子：
3.5
作者：
Forsythe, E.;Sparks, K.;Beales, P. L.
通讯作者：
Beales, P. L.
DOI：
10.2215/cjn.03320410
发表时间：
2011-01-01
影响因子：
9.8
作者：
Imhoff, Olivier;Marion, Vincent;Moulin, Bruno
通讯作者：
Moulin, Bruno
影响因子：
5.2
作者：
Forsythe, Elizabeth;Beales, Philip L.
通讯作者：
Beales, Philip L.