Department of Pediatrics, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Chin Med J (Engl). 2012 Feb;125(3):496-501.
Cardiovascular complications of Kawasaki disease (KD) are a common cause of heart disease in pediatric populations. Previous studies have suggested a role for endothelial progenitor cells (EPCs) in coronary artery lesions associated with KD. However, long-term observations of EPCs during the natural progression of this disorder are lacking. Using an experimental model of KD, we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.
To induce KD, C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE; phosphate buffered saline used as control vehicle). Study groups included: group A (14 days following LCWE injection), group B (56 days following LCWE injection) and group C (controls). Numbers of circulating EPCs (positively staining for both CD34 and Flk-1 while staining negative for CD45) were evaluated using flow cytometry. Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis. In vitro EPC proliferation, adhesion and migration were assessed.
The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms. Numbers of circulating EPCs decreased significantly in the KD models (groups A and B) compared to controls ((0.017 ± 0.008)% vs. (0.028 ± 0.007)%, P < 0.05 and (0.016 ± 0.007)% vs. (0.028 ± 0.007)%, P < 0.05). Proliferative, adhesive and migratory properties of EPCs were markedly impaired in groups A and B.
Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair, resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.
川崎病（KD）的心血管并发症是儿科人群心脏病的常见原因。先前的研究表明内皮祖细胞（EPCs）在与 KD 相关的冠状动脉病变中起作用。然而，这种疾病自然进展过程中 EPCs 的长期观察结果尚缺乏。我们使用 KD 的实验模型，旨在确定冠状动脉病变是否与 EPC 下调有关。
为了诱导 KD，C57BL/6 小鼠接受了酪酸梭菌细胞壁提取物（LCWE；磷酸盐缓冲盐水用作对照载体）的腹腔内注射。研究组包括：A 组（LCWE 注射后 14 天）、B 组（LCWE 注射后 56 天）和 C 组（对照组）。使用流式细胞术评估循环 EPCs（同时对 CD34 和 Flk-1 呈阳性而对 CD45 呈阴性）的数量。将骨髓单核细胞在体外培养以扩增 EPC 进行功能分析。评估体外 EPC 增殖、黏附和迁移。
该模型显示出与 KD 患者伴冠状动脉瘤的类似冠状动脉病变。与对照组相比，KD 模型（A 组和 B 组）中循环 EPCs 的数量明显减少（（0.017 ± 0.008）%比（0.028 ± 0.007）%，P < 0.05 和（0.016 ± 0.007）%比（0.028 ± 0.007）%，P < 0.05）。A 组和 B 组中 EPC 的增殖、黏附和迁移特性明显受损。
KD 中的冠状动脉病变是由于 EPC 过度消耗以及骨髓 EPC 及其前体的功能障碍导致血管损伤修复受损而发生的。
