Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.
Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.
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DOI：
10.1016/j.atherosclerosis.2016.07.930
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发表时间：
2016-09
期刊：
影响因子：
5.3
通讯作者：
Tarbell, John M.
中科院分区：
文献类型：
--
作者：
Cancel, Limary M.;Ebong, Eno E.;Mensah, Solomon;Hirschberg, Carly;Tarbell, John M.
先前的实验表明，增加的内皮细胞凋亡和内皮表面糖萼脱落可能在血管系统的动脉粥样硬化倾向区域的内皮功能障碍和炎症中起作用。我们试图阐明内皮细胞凋亡和糖萼脱落促进动脉粥样硬化形成的可能协同机制。4-给6周龄的雄性C57 Bl/6载脂蛋白E敲除（ApoE-/-）小鼠喂食西方饮食10周，并在其头臂动脉中形成斑块。与非斑块区域相比，斑块区域的糖萼覆盖率和厚度显著降低（斑块覆盖率：71± 23%，非斑块：97± 3%，p= 0.02;斑块厚度：0.85±0.15 μm，非斑块：1.2±0.21 μm，p= 0.006）。非斑块区域的数值与饲喂正常饲料的野生型小鼠中的数值无差异（覆盖率WT：92± 3%，p= 0.7 vs.非斑块ApoE−/−，厚度WT：1.1±0.06 μm，p= 0.2 vs.非斑块ApoE−/−）。与野生型小鼠相比，Apoe-/-小鼠的内皮细胞凋亡显着增加（Apoe-/-：64.3±33.0，WT：1.1±0.5 TunEL-pos/cm，p= 2×10 - 7）。同一血管斑块区每单位长度的凋亡内皮细胞数是非斑块区的2倍（p= 3×10−5）。基质金属蛋白酶9的表达增加与糖萼脱落和斑块积聚共定位。我们的研究结果表明，与内皮细胞凋亡，增加脂质渗透性，炎症引发的糖萼脱落促进单核细胞粘附和巨噬细胞浸润，促进脂质潴留和动脉粥样硬化斑块的发展。
Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis. 4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE−/−) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries. Glycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71±23%, non-plaque: 97±3%, p= 0.02; thickness plaque: 0.85±0.15 μm, non-plaque: 1.2±0.21 μm, p= 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92±3%, p= 0.7 vs. non-plaque ApoE−/−, thickness WT: 1.1±0.06 μm, p= 0.2 vs. non-plaque ApoE−/−). Endothelial cell apoptosis was significantly increased in ApoE−/− mice compared to wild type mice (ApoE−/− :64.3±33.0, WT: 1.1±0.5 TUNEL-pos/cm, p= 2×10−7). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel (p= 3×10−5). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup. Our results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques.
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