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本帖最后由 hzangs 于 2015-12-15 10:31 编辑
5月20日 Circulation：心脏压力过载产生的外泌体含有功能性血管紧缩素Ⅱ的Ⅰ型受体
目前尚不清楚心脏上的生物力学是否能够诱导外泌体的分泌从而调节心血管的功能。来自杜克大学的研究者们研究了心脏外泌体的分泌和活力，这类外泌体含有一个在心血管功能调节中起关键调节作用的受体——血管紧缩素Ⅱ的Ⅰ型受体（Angiotensin II Type I Receptor, AT1R）。从心脏压力过载的小鼠血清中和受渗透压...(osmotic stretch怎么翻译？囧)过表达AT1R细胞的细胞上清中提取的外泌体富含AT1Rs。并且发现这种外泌体是有心肌细胞分泌的。外源性给予富含AT1Rs的外泌体处理心肌细胞、骨骼肌细胞、肠系膜阻力血管（mesenteric resistance vessels,是这么翻译的么？囧）均能在AT1R敲出小鼠中rescue angiotensin II对blood pressure的反应。
Pironti, G., Strachan, R. T., Abraham, D., Yu, S. M., Chen, M., Chen, W., . . . Rockman, H. A. (2015). Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors. Circulation. doi: 10.1161/CIRCULATIONAHA.115.015687
Background—Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the Angiotensin II Type I Receptor (AT1R).
Methods and Results—Exosomes containing AT1Rs were isolated from the media overlying AT1R-overexpressing cells exposed to osmotic stretch and from sera of mice undergoing cardiac pressure overload. The presence of AT1Rs in exosomes was confirmed by both electron microscopy and radioligand receptor binding assays, and shown to require ȕ-arrestin2, a multifunctional adaptor protein essential for receptor trafficking. We show that functional AT1Rs are transferred via exosomes in an in vitro model of cellular stretch. Using mice with global and cardiomyocyte conditional deletion ofE-arrestin2, we show that under conditions of in vivo pressure overload the cellular source for the exocytosis of exosomes containing AT1R is the cardiomyocyte. Exogenous administered AT1R-enriched exosomes target cardiomyocytes, skeletal myocytes and mesenteric resistance vessels, and is sufficient to confer blood pressure responsiveness to angiotensin II infusion in AT1R knockout mice.
Conclusions—This work reveals that AT1R-enriched exosomes are released from the heart under conditions of in vivo cellular stress to likely modulate vascular responses to neurohormonal stimulation. In the context of the whole organism, the concept of G proteincoupled receptor trafficking should consider circulating exosomes as part of the reservoir of functional AT1Rs.
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|Archiver|手机版|外泌体之家 | exosomes & microvesicles
发表于 2015-5-24 19:14:20
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发表于 2015-5-25 09:32:48
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