Hemodynamic regulation of CD34+ cell localization and differentiation in experimental aneurysms
Hemodynamic regulation of CD34+ cell localization and differentiation in experimental aneurysms
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DOI：
10.1161/01.atv.0000142805.20398.74
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发表时间：
2004-10-01
影响因子：
8.7
通讯作者：
Dalman, RL
中科院分区：
文献类型：
--
作者：
Sho, E;Sho, M;Dalman, RL
目的：骨髓来源的血管祖细胞(CD34(+))存在于腹主动脉瘤(AAA)疾病的人和动物模型中。这些终末期前分化的细胞可能调节抗病能力。我们检测了不同的血流动力学条件对实验性AAA中祖细胞定位和分化的影响。方法和结果-通过猪胰腺弹性酶(PPE)输注建立小鼠AAA。腹主动脉血流量通过腹主动脉瘘(ACF)的形成而增加(HF-AAA)，通过左髂骨结扎(LF-AAA)而减少，或保持不变(NF-AAA)。与基线(0.6+/-0.1毫升/分钟)相比，ACF使血流量增加1700%，而髂骨结扎使血流量减少79%。静脉注射PPE后第14天，HF-AAA组的室壁切应力(WSS)相应增加或降低，并持续升高(9.2+/-2.0dynes/cm(2))。CD34(+)细胞在所有血流状态下均可见于主动脉壁。注射PPE后7d，HF-AAA组CD34(+)细胞数较LF-AAA组多(187+/-10vs155+/-7个CD34(+)细胞/横截面，P<；0.05)，中层平滑肌细胞较多，巨噬细胞较少，直径较小。LF-AAA还含有更多的外膜毛细血管(HF-AAA的CD34(+)毛细血管181+/-12比89+/-32/横截面积，P<；0.05)。总祖细胞/毛细血管指数(CD34(+)毛细血管+CD31(+)毛细血管/横截面积)高于LF-AAA组(282+/-31比129+/-47，P<0.05)。血管内皮细胞(VEGF)和血小板衍生生长因子(PDGF)的表达与组间毛细血管密度呈正相关。粒细胞巨噬细胞集落刺激因子(GM-CSF)在LF-AAA中表达增加。结论血流动力学条件影响实验性AAA中CD34(+)细胞的定位和分化。外膜毛细血管生成可能促进炎症和疾病进展。调节成熟祖细胞的细胞谱系分化可能代表了一种新的治疗策略，以维持AAA病的中层细胞密度和细胞外基质的完整性。
Objectives - Bone marrow-derived vascular progenitor cells (CD34(+)) are present in human and animal models of abdominal aortic aneurysm (AAA) disease. These preterminally differentiated cells may modulate disease resistance. We examined the influence of variable hemodynamic conditions on progenitor cell localization and differentiation in experimental AAAs.Methods and Results - Murine AAAs were created via porcine pancreatic elastase (PPE) infusion. AAA blood flow was increased by aortocaval fistula (ACF) formation (HF-AAA), decreased via left iliac ligation (LF-AAA), or left unchanged (NF-AAA). ACF creation increased flow by 1700%, whereas iliac ligation decreased flow 79% compared with baseline (0.6 +/- 0.1 mL/min). Wall shear stress (WSS) increased or decreased accordingly, and remained elevated (9.2 +/- 2.0 dynes/cm(2)) in HF-AAA 14 days after PPE infusion. CD34(+) cells were identified throughout the aortic wall in all flow conditions. Seven days after PPE infusion, HF-AAAs had more CD34(+) cells than LF-AAA (187 +/- 10 versus 155 +/- 7 CD34(+) cells/cross sectional, P < 0.05), more medial smooth muscle cells, fewer infiltrative macrophages, and a smaller diameter than LF-AAA. LF-AAAs also contained more adventitial capillaries (CD34(+) capillaries 181 +/- 12 versus 89 +/- 32/cross-sectional area in HF-AAA, P < 0.05). The total progenitor cell/capillary index (CD34(+) capillary plus CD31(+) capillary/cross sectional area) was higher in LF-AAA (282 +/- 31 versus 129 +/- 47, P < 0.05). Vascular endothelial (VEGF) and platelet-derived growth factor (PDGF) expression varied directly with capillary density between groups. Increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression was also present in LF-AAAs.Conclusions - Hemodynamic conditions influence CD34(+) cell localization and differentiation in experimental AAA. Adventitial capillary angiogenesis may augment inflammation and disease progression. Modulating cell lineage differentiation of mature progenitor cells may represent a novel therapeutic strategy to maintain medial cellularity and extracellular matrix integrity in AAA disease.