Department of Cardiology and Pulmonology, University of Göttingen, Göttingen, Germany.
J Am Coll Cardiol. 2010 Jan 26;55(4):357-67. doi: 10.1016/j.jacc.2009.09.031.
The purpose of this study was to examine the impact of obesity and weight loss on the angiogenic and regenerative capacity of endothelial progenitor cells (EPCs).
EPCs participate in angiogenesis and tissue repair. Several cardiovascular risk factors are associated with EPC dysfunction.
Early outgrowth EPCs were isolated from 49 obese (age 42 +/- 14 years; body mass index 42 +/- 7 kg/m(2)) normoglycemic participants in a professional weight reduction program and compared with those from 49 age-matched lean controls. EPC function was tested both in vitro and in vivo.
EPCs expanded from the obese possessed reduced adhesive, migratory, and angiogenic capacity, and mice treated with obese EPCs exhibited reduced EPC homing in ischemic hind limbs in vivo. EPCs from the obese subjects failed to respond to conditioned medium of lean controls or to potent angiogenic factors such as vascular endothelial growth factor. Although no differences existed between lean and obese EPCs regarding the surface expression of vascular endothelial growth factor or chemokine receptors, basal p38 mitogen-activated protein kinase (MAPK) phosphorylation was elevated in obese EPCs (3.7 +/- 2.1-fold increase; p = 0.006). These cells also showed reduced secretion of the angiogenic chemokines interleukin-8 (p = 0.047) and monocyte chemoattractant protein-1 (p = 0.012). By inhibiting p38 MAPK, we could restore chemokine levels to those of lean control EPCs and also improve the angiogenic properties of obese EPCs. Accordingly, 6-month follow-up of 26 obese persons who achieved significant weight reduction revealed normalization of p38 MAPK phosphorylation levels and improved EPC function.
Obesity is associated with a reversible functional impairment of EPCs. This involves reduced secretion of angiogenic chemokines and increased basal phosphorylation of signaling molecules, notably p38 MAPK.
本研究旨在探讨肥胖和体重减轻对内皮祖细胞（EPC）的血管生成和再生能力的影响。
EPC 参与血管生成和组织修复。一些心血管危险因素与 EPC 功能障碍有关。
从 49 名参加专业减肥计划的肥胖（年龄 42±14 岁；体重指数 42±7kg/m²）的正常血糖参与者中分离早期生长 EPC，并与 49 名年龄匹配的瘦对照者进行比较。在体外和体内测试 EPC 功能。
从肥胖者中扩增的 EPC 具有降低的黏附、迁移和血管生成能力，并且用肥胖者的 EPC 治疗的小鼠在体内缺血性后肢中表现出减少的 EPC 归巢。肥胖者的 EPC 对瘦对照组的条件培养基或血管内皮生长因子等有效的血管生成因子无反应。虽然瘦和肥胖者的 EPC 在血管内皮生长因子或趋化因子受体的表面表达上没有差异，但肥胖者的 EPC 中基础 p38 丝裂原活化蛋白激酶（MAPK）磷酸化水平升高（增加 3.7±2.1 倍；p=0.006）。这些细胞也显示出降低的血管生成趋化因子白细胞介素-8（p=0.047）和单核细胞趋化蛋白-1（p=0.012）的分泌。通过抑制 p38 MAPK，我们可以将趋化因子水平恢复到瘦对照组 EPC 的水平，并改善肥胖者 EPC 的血管生成特性。因此，对 26 名体重显著减轻的肥胖者进行 6 个月的随访显示，p38 MAPK 磷酸化水平正常化和 EPC 功能改善。
肥胖与 EPC 的功能障碍有关，这种障碍涉及到血管生成趋化因子分泌减少和信号分子，特别是 p38 MAPK 的基础磷酸化增加。
