Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Atherosclerosis. 2011 Nov;219(1):92-9. doi: 10.1016/j.atherosclerosis.2011.07.118. Epub 2011 Aug 4.
Reduced numbers and activity of circulating progenitor cells are associated with aging and have been linked with coronary artery disease. To determine the impact of aging and atherosclerotic disease on the chemotaxic activity of bone marrow derived cells (BMCs), we examined CXCR4 surface expression on BMCs from aged and atherosclerotic mice.
CXCR4 expression and cellular mobility were compared between BMCs of young (6-week old) ApoE null mice (ApoE(-/-)) and aged ApoE(-/-) mice that had been fed with a high-fat, high-cholesterol diet for 6-months.
Age and atherosclerosis correlated with significantly lower surface expression of CXCR4 that was less inducible by calcium. The impaired calcium response was associated with defective calcium influx and was partially recovered by treatment with the calcium ionophore ionomycin. ApoE(-/-) mice fed high fat diet for 6-months had defective CXCR4 expression and SDF-1 regulation that is equivalent to that of 24-month old wild type mice. BMCs from aged, atherogenic ApoE(-/-) mice also displayed defective homing to SDF-1, and the animals had lower serum and bone marrow levels of SDF-1.
Evolution of atherosclerosis in ApoE(-/-) mice is paralleled by progressive loss of mobility of BMCs with reductions of CXCR4 expression, and reduced levels of SDF-1 in both serum and bone marrow. These changes mute the homing capability of BMCs and may contribute to the progression of atherosclerosis in this model.
循环祖细胞数量和活性的减少与衰老有关，并与冠状动脉疾病有关。为了确定衰老和动脉粥样硬化疾病对骨髓来源细胞（BMCs）的趋化活性的影响，我们检测了来自衰老和动脉粥样硬化小鼠的 BMCs 上 CXCR4 的表面表达。
比较了年轻（6 周龄）ApoE 基因敲除小鼠（ApoE(-/-)）和高脂高胆固醇饮食喂养 6 个月的衰老 ApoE(-/-) 小鼠的 BMCs 之间 CXCR4 的表达和细胞迁移。
年龄和动脉粥样硬化与 CXCR4 表面表达显著降低相关，而钙诱导的 CXCR4 表达降低更为明显。受损的钙反应与钙内流缺陷有关，部分通过钙载体离子霉素处理得到恢复。用高脂肪饮食喂养 6 个月的 ApoE(-/-) 小鼠表现出 CXCR4 表达和 SDF-1 调节缺陷，相当于 24 月龄野生型小鼠。来自衰老、动脉粥样硬化的 ApoE(-/-) 小鼠的 BMCs 也显示出向 SDF-1 的归巢能力受损，并且动物的血清和骨髓中的 SDF-1 水平较低。
apoE(-/-)小鼠动脉粥样硬化的发生与 BMCs 的迁移能力逐渐丧失、CXCR4 表达减少以及血清和骨髓中 SDF-1 水平降低相一致。这些变化削弱了 BMCs 的归巢能力，可能导致该模型中动脉粥样硬化的进展。
