Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA.
Obesity (Silver Spring). 2010 Sep;18(9):1677-82. doi: 10.1038/oby.2009.494. Epub 2010 Jan 7.
Excess adiposity is associated with increased cardiovascular morbidity and mortality. Endothelial progenitor cells (EPCs) play an important role in vascular repair. We tested the hypothesis that increased adiposity is associated with EPC dysfunction, characterized by diminished capacity to release angiogenic cytokines, increased apoptotic susceptibility, reduced cell migration, and shorter telomere length. A total of 67 middle-aged and older adults (42-67 years) were studied: 25 normal weight (normal weight; BMI: 18.5-24.9 kg/m(2)) and 42 overweight/obese (overweight/obese; BMI: 25.0-34.9 kg/m(2)). Cells with phenotypic EPC characteristics were isolated from peripheral blood. EPC release of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF) was determined in the absence and presence of phytohemagglutinin (10 microg/ml). Intracellular active caspase-3 and cytochrome c concentrations were determined by immunoassay. Migratory activity of EPCs in response to VEGF (2 ng/ml) and stromal cell-derived factor-1alpha (SDF-1alpha; 10 ng/ml) was determined by Boyden chamber. Telomere length was assessed by Southern hybridization. Phytohemagglutinin-stimulated release of VEGF (90.6 +/- 7.6 vs. 127.2 +/- 11.6 pg/ml) and G-CSF (896.1 +/- 77.4 vs. 1,176.3 +/- 126.3 pg/ml) was ~25% lower (P < 0.05) in EPCs from overweight/obese vs. normal weight subjects. Staurosporine induced a ~30% greater (P < 0.05) increase in active caspase-3 in EPCs from overweight/obese (2.8 +/- 0.2 ng/ml) compared with normal weight (2.2 +/- 0.2) subjects. There were no significant differences in EPC migration to either VEGF or SDF-1alpha. Telomere length did not differ between groups. These results indicate that increased adiposity adversely affects the ability of EPCs to release proangiogenic cytokines and resist apoptosis, potentially compromising their reparative potential.
肥胖与心血管发病率和死亡率的增加有关。内皮祖细胞 (EPC) 在血管修复中起着重要作用。我们验证了这样一个假设，即肥胖与 EPC 功能障碍有关，其特征是释放血管生成细胞因子的能力降低、凋亡易感性增加、细胞迁移减少和端粒缩短。共研究了 67 名中老年人（42-67 岁）：25 名正常体重（正常体重；BMI：18.5-24.9kg/m(2)) 和 42 名超重/肥胖（超重/肥胖；BMI：25.0-34.9kg/m(2))。从外周血中分离出具有表型 EPC 特征的细胞。在无植物血凝素 (10μg/ml) 和存在植物血凝素的情况下，测定血管内皮生长因子 (VEGF) 和粒细胞集落刺激因子 (G-CSF) 的 EPC 释放。通过免疫测定法测定细胞内活性半胱天冬酶-3 和细胞色素 c 的浓度。通过 Boyden 室测定 VEGF（2ng/ml）和基质细胞衍生因子-1alpha（SDF-1alpha；10ng/ml）刺激下 EPC 的迁移活性。通过 Southern 杂交评估端粒长度。植物血凝素刺激的 VEGF（90.6+/-7.6vs.127.2+/-11.6pg/ml）和 G-CSF（896.1+/-77.4vs.1,176.3+/-126.3pg/ml）释放在超重/肥胖患者的 EPC 中比正常体重患者低约 25%（P<0.05）。在超重/肥胖（2.8+/-0.2ng/ml）与正常体重（2.2+/-0.2）受试者中，Staurosporine 诱导的活性半胱天冬酶-3 增加约 30%（P<0.05）。EPC 向 VEGF 或 SDF-1alpha 的迁移没有差异。两组之间的端粒长度没有差异。这些结果表明，肥胖会对 EPC 释放促血管生成细胞因子和抵抗凋亡的能力产生不利影响，从而降低其修复潜力。
