Rapid Endothelial Turnover in Atherosclerosis-Prone Areas Coincides With Stem Cell Repair in Apolipoprotein E–Deficient Mice

Author:

Foteinos Georgios1,Hu Yanhua1,Xiao Qingzhong1,Metzler Bernhard1,Xu Qingbo1

Affiliation:

1. From the Department of Cardiac and Vascular Sciences, St George’s University of London, London, UK (G.F.); Department of Cardiology, Medical University of Innsbruck, Innsbruck, Austria (B.M.); and Cardiovascular Division, King’s College London, London, UK (Y.H., Q. Xiao, Q. Xu).

Abstract

Background— Recently, it has been shown that stem/progenitor cells may repair damaged/lost endothelial cells in vein grafts and wire-injured arteries. In the present study, we investigated endothelial cell turnover and regeneration in apolipoprotein E (apoE) −/− /transgenic mice carrying LacZ genes driven by an endothelial TIE2 promoter. Methods and Results— To assess cell proliferation on the surface of aortas in apoE −/− mice and wild-type controls, BrdU was injected into the tail vein and labeled on en face preparation. BrdU-positive cells on the aortas were observed occasionally in wild-type mice and frequently at sites prone to lesion development in apoE −/− mice (0.18±0.1% versus 1.12±0.2%; P <0.001). Endothelial integrity tests demonstrated that the areas with high rate of cell turnover displayed Evans blue leakage, low levels of VE-cadherin expression, and increased cell attachment, as evidenced by Evans blue dye injection, immunostaining, and scanning electron microscopy, respectively. Furthermore, immunostaining for CD34, Sca-1, Flk-1, and CD133 indicated that ≈3% to 5% of total cells on the aorta were positive in apoE −/− mice. En face double labeling using Ki-67 and progenitor markers revealed that 30% to 50% of progenitor + cells expressed Ki-67, indicating a state of proliferation. To clarify the origin of endothelial progenitor cells participating in endothelial repair in apoE −/− mice, a chimeric mouse model was created by bone marrow transplantation between apoE −/− and LacZ +/+ /apoE −/− mice. Ten months after bone marrow transplantation, ≈3% to 4% of total cells in the lesion-prone areas were β-gal positive in apoE −/− with apoE −/− /TIE2-LacZ bone marrow mice. When cells of aortas from chimeric mice were cultivated on Matrigel-coated plates, a capillary-like structure was found, which showed β-gal/CD31 or β-gal/von Willebrand factor double positivity. By a combined analysis of laser dissection microscopy and nest reverse transcription polymerase chain reaction, it was found that β-gal + cells were mainly expressing CD31 and CD144. Conclusions— Our findings provide the first quantitative data on endothelial turnover and repair by progenitor cells that are, at least in part, derived from bone marrow during development of atherosclerosis in apoE −/− mice.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Cited by 156 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3