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Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema

机译:通过刺激肺肺部血管生成促进EP2受体激动剂促进脂肪组织

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Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE(2), we examined whether ONO-AEI-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AEI -259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AEI -259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component. (C) 2014 Elsevier Inc. All rights reserved.
机译:体重减轻是慢性阻塞性肺病(COPD),特别是具有严重肺气肿的患者的常见表现。脂肪血管生成是脂肪生成的关键介质,并且使用促血管生成剂的使用可以作为瘦患者的治疗选择。由于PGE(2)刺激血管生成,我们检查了ONO-AEI-259,一种选择性E-前列醇(EP)2受体激动剂,可促进脂肪酶诱导的肺气肿的小鼠模型中的脂肪血管生成和脂肪发生(EIE小鼠)。用弹性蛋白酶或盐水肿瘤滴注小鼠,然后通过腹膜内施用ONO-AE1-259进行4周后4周。皮下脂肪组织(SAT)重量在eie小鼠中减少,而在用ONO-AE1-259处理的EIE小鼠中,饱和重量大大恢复,其与饱和脂肪发生,血管生成和VEGF蛋白质产生的显着增加有关。相比之下,ONO-AEI -259给药诱导在内脏脂肪组织的重量中没有改变。这些结果表明,在eie小鼠中,Ono-aei -259可能通过VEGF生产和脂肪发生刺激脂肪血管生成。我们的数据铺平了肺气肿患者体重减轻的治疗干预措施的方法,例如,使用靶向脂肪组织血管组分的促血管生成剂。 (c)2014年elsevier Inc.保留所有权利。

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