Moderate Alcohol Consumption Targets S100β(+) Vascular Stem Cells and Attenuates Injury-Induced Neointimal Hyperplasia.
Moderate Alcohol Consumption Targets S100β(+) Vascular Stem Cells and Attenuates Injury-Induced Neointimal Hyperplasia.
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DOI：
10.1111/acer.14415
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Redmond EM
中科院分区：
文献类型：
--
作者：
Liu W;Harman S;DiLuca M;Burtenshaw D;Corcoran E;Cahill PA;Redmond EM
存在于血管壁上的干细胞可能在对有害刺激的反应中被触发进行分化并促进血管疾病的发展。我们的目的是确定适度酒精（EtOH）暴露对S100钙结合蛋白B阳性（S100β+）常驻血管干细胞的扩张和分化的影响，以及它们在动脉硬化小鼠模型中对病理性血管重塑的贡献。对S100β- egfp /Cre/ ERT2-dTomato转基因雄性和雌性小鼠进行S100β+细胞谱系追踪分析，在左颈总动脉结扎后，每天口服或不口服EtOH（峰值BAC: 15mM或0.07%）灌胃。采集颈动脉（结扎或假手术）进行形态学分析，并在FFPE颈动脉横截面上对荧光标记的S100β +细胞进行共聚焦评估。结扎诱导的颈动脉重构在男性中比在女性中更为强健。与对照组相比，etoh灌胃小鼠的外膜增厚较少，新内膜形成明显减少，雄性小鼠的抑制作用比雌性小鼠更明显。结扎后血管中S100β +标记细胞显著扩增，主要在新内膜室。EtOH治疗降低了颈动脉横截面上S100β +细胞的比例，并伴有减轻的重构。在体外，EtOH可以减弱Sonic hedgehog刺激的小鼠S100β +血管干细胞的成肌分化（calponin和myosin重链表达减少）。这些数据强调了常驻血管S100β +干细胞作为酒精的新靶标群体，并表明成人动脉（特别是男性）中这些祖细胞的调节可能是适度饮酒抗动脉粥样硬化作用的重要机制。
Stem cells present in the vessel wall may be triggered in response to injurious stimuli to undergo differentiation and contribute to vascular disease development. Our aim was to determine the effect of moderate alcohol (EtOH) exposure on the expansion and differentiation of S100 calcium-binding protein B positive (S100β+) resident vascular stem cells and their contribution to pathologic vessel remodeling in a mouse model of arteriosclerosis. Lineage tracing analysis of S100β+ cells was performed in male and female S100β-eGFP/Cre/ERT2–dTomato transgenic mice treated daily with or without EtOH by oral gavage (peak BAC: 15mM or 0.07%) following left common carotid artery ligation for 14 days. Carotid arteries (ligated or sham-operated) were harvested for morphological analysis and confocal assessment of fluorescent-tagged S100β + cells in FFPE carotid cross sections. Ligation-induced carotid remodeling was more robust in males than in females. EtOH-gavaged mice had less adventitial thickening and markedly reduced neo-intimal formation compared to controls, with a more pronounced inhibitory effect in males compared to females. There was significant expansion of S100β + marked cells in vessels post-ligation, primarily in the neo-intimal compartment. EtOH treatment reduced the fraction of S100β + cells in carotid cross-sections, concomitant with attenuated remodeling. In vitro, EtOH attenuated Sonic Hedgehog-stimulated myogenic differentiation (as evidenced by reduced calponin and myosin heavy chain expression) of isolated murine S100β + vascular stem cells. These data highlight resident vascular S100β + stem cells as a novel target population for alcohol, and suggest that regulation of these progenitors in adult arteries, particularly in males, may be an important mechanism contributing to the anti-atherogenic effects of moderate alcohol consumption.
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DOI：
10.1161/atvbaha.116.307301
发表时间：
2017-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Arnold AP;Cassis LA;Eghbali M;Reue K;Sandberg K
通讯作者：
Sandberg K
DOI：
10.1152/ajpheart.00160.2012
发表时间：
2012-12-01
影响因子：
4.8
作者：
Li, Haijie;Li, Jingjing;Zheng, Xi-Long
通讯作者：
Zheng, Xi-Long
影响因子：
6.7
作者：
Milla, Luis A;González-Ramírez, Claudia N;Palma, Verónica
通讯作者：
Palma, Verónica
影响因子：
7.4
作者：
Abou-Agag, LH;Khoo, NK;Parks, DA
通讯作者：
Parks, DA
DOI：
10.1111/acer.13499
发表时间：
2017-12
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Fitzpatrick E;Han X;Liu W;Corcoran E;Burtenshaw D;Morrow D;Helt JC;Cahill PA;Redmond EM
通讯作者：
Redmond EM