Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion
Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion
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DOI：
10.1161/circresaha.107.169375
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发表时间：
2008-08-29
影响因子：
20.1
通讯作者：
Schaefer, Katrin
中科院分区：
文献类型：
--
作者：
Schroeter, Marco R.;Leifheit, Maren;Schaefer, Katrin
脂肪细胞因子瘦素调节血管重塑和新生内膜形成。由于内皮祖细胞（EPCs）参与血管修复，我们分析了瘦素对人内皮祖细胞功能的影响，在体外和体内。培养7天后，EPCs表达瘦素受体，并对瘦素刺激作出反应，增加STAT 3磷酸化。EPCs与瘦素（浓度在1和100 ng/mL之间）的孵育增加了EPCs以受体特异性方式粘附到玻连蛋白和纤连蛋白的数量。它还增强了EPCs整合到单层人内皮细胞中的能力以及这些细胞与活化血小板的粘附。瘦素上调α v β 5和α 4整合素在EPCs中的表达，并且瘦素对EPC功能的影响可以被RGD肽和功能阻断抗体至少部分地阻止。静脉注射荧光标记的人EPCs到无胸腺裸鼠血管损伤后不久，发现EPCs与瘦素的预孵育增加了内膜病变内的积累，加速再内皮化和减少新生内膜形成的α v β 5和α 4整合素依赖的方式。我们的研究结果表明，瘦素特异性地调节EPCs的粘附特性和归巢潜力，从而增强其促进体内血管再生的能力。(Circ Res. 2008; 103：536-544）。
The adipocytokine leptin modulates vascular remodeling and neointima formation. Because endothelial progenitor cells (EPCs) participate in vascular repair, we analyzed the effects of leptin on human EPC function in vitro and in vivo. After 7 days in culture, EPCs expressed the leptin receptor and responded to leptin stimulation with increased STAT3 phosphorylation. Incubation of EPCs with leptin (at concentrations between 1 and 100 ng/mL) increased the number of EPCs adhering to vitronectin and fibronectin in a receptor-specific manner. It also enhanced the capacity of EPCs to incorporate into a monolayer of human endothelial cells and the adherence of these cells to activated platelets. Leptin upregulated alpha v beta 5 and alpha 4 integrin expression in EPCs, and the effects of leptin on EPC function could be prevented, at least in part, by RGD peptides and function-blocking antibodies. Intravenous injection of fluorescently labeled human EPCs into athymic nude mice shortly after vascular injury revealed that preincubation of EPCs with leptin augmented their accumulation within intimal lesions, accelerating reendothelialization and decreasing neointima formation in an alpha v beta 5 and alpha 4 integrin-dependent manner. Our findings suggest that leptin specifically modulates the adhesive properties and the homing potential of EPCs and may thus enhance their capacity to promote vascular regeneration in vivo. (Circ Res. 2008; 103: 536-544.)