衰老、祖细胞耗竭与动脉粥样硬化。
Aging, progenitor cell exhaustion, and atherosclerosis.
作者信息
Rauscher Frederick M, Goldschmidt-Clermont Pascal J, Davis Bryce H, Wang Tao, Gregg David, Ramaswami Priya, Pippen Anne M, Annex Brian H, Dong Chunming, Taylor Doris A
机构信息
Division of Cardiology, Department of Medicine, Duke University Medical Center, Box 3845, Durham, NC 27710, USA.
出版信息
Circulation. 2003 Jul 29;108(4):457-63. doi: 10.1161/01.CIR.0000082924.75945.48. Epub 2003 Jul 14.
BACKGROUND
Atherosclerosis is largely attributed to chronic vascular injury, as occurs with excess cholesterol; however, the effect of concomitant vascular aging remains unexplained. We hypothesize that the effect of time in atherosclerosis progression is related to obsolescence of endogenous progenitor cells that normally repair and rejuvenate the arteries.
METHODS AND RESULTS
Here we show that chronic treatment with bone marrow-derived progenitor cells from young nonatherosclerotic ApoE-/- mice prevents atherosclerosis progression in ApoE-/- recipients despite persistent hypercholesterolemia. In contrast, treatment with bone marrow cells from older ApoE-/- mice with atherosclerosis is much less effective. Cells with vascular progenitor potential are decreased in the bone marrow of aging ApoE-/- mice, but cells injected from donor mice engraft on recipient arteries in areas at risk for atherosclerotic injury.
CONCLUSIONS
Our data indicate that progressive progenitor cell deficits may contribute to the development of atherosclerosis.
背景
动脉粥样硬化很大程度上归因于慢性血管损伤，如高胆固醇血症时发生的情况；然而，伴随血管衰老的影响仍无法解释。我们推测，时间对动脉粥样硬化进展的影响与内源性祖细胞的衰老有关，这些祖细胞通常负责修复和使动脉恢复活力。
方法与结果
在此我们表明，用来自年轻非动脉粥样硬化ApoE-/-小鼠的骨髓源性祖细胞进行长期治疗，可防止ApoE-/-受体发生动脉粥样硬化进展，尽管持续存在高胆固醇血症。相比之下，用患有动脉粥样硬化的老年ApoE-/-小鼠的骨髓细胞进行治疗效果要差得多。具有血管祖细胞潜能的细胞在衰老的ApoE-/-小鼠骨髓中减少，但从供体小鼠注射的细胞可植入受体动脉中存在动脉粥样硬化损伤风险的区域。
结论
我们的数据表明，祖细胞的逐渐缺乏可能导致动脉粥样硬化的发展。
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