Department of Internal Medicine II, Medical University of Vienna, A-1090 Vienna, Austria.
5th Medical Department for Endocrinology and Rheumatology, Wilhelminenhospital, A-1160 Vienna, Austria.
Int J Mol Sci. 2019 Apr 30;20(9):2153. doi: 10.3390/ijms20092153.
Circulating extracellular vesicles are small particles enclosed by a phospholipid bilayer. Vesicles deriving directly from the cellular membrane by an active budding process retain cell origin specific proteins and RNA. These vesicles carry pathophysiological information from their parental cell and hold the potential to allow analysis of organs without the need for a biopsy. We included in our study 27 patients undergoing bariatric surgery. Hepatic extracellular vesicles were determined by flow cytometry. mRNA specific for hepatic cellular origin was determined in the extracellular vesicle fraction using qPCR. Surgery led to a massive reduction of weight and overall hepatic stress as determined by alanine transaminase (ALT), aspartate transaminase (AST) and γ-glutamyltransferase (GGT). Total extracellular vesicle numbers were reduced after bariatric surgery. Liver specific vesicles identified by HepPar1 or asialoglycoprotein receptor (ASGPR) were significantly reduced after bariatric surgery in both AnnexinV and AnnexinV subgroups. When analyzing circulating liver-specific mRNAs, we found reduced levels of these mRNAs after surgery even though total circulating RNA remained unchanged. We conclude that circulating hepatic extracellular vesicles are detectable in samples from patients undergoing gastric bypass surgery. These vesicles are reduced after a reduction of hepatic stress also observed with classic liver enzyme measurements. We conclude that ASGPR or HepPar positive vesicles hold the potential to serve as liver specific vesicle markers.
循环细胞外囊泡是由磷脂双层包裹的小颗粒。通过主动出芽过程直接从细胞膜衍生而来的囊泡保留了细胞来源特异性的蛋白质和 RNA。这些囊泡携带来自其亲本细胞的病理生理信息，并有可能在不需要活检的情况下分析器官。我们纳入了 27 例接受减肥手术的患者。通过流式细胞术测定肝细胞外囊泡。使用 qPCR 在外泌体部分测定肝源性细胞特异性的 mRNA。手术导致体重和丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST) 和γ-谷氨酰转移酶 (GGT) 等整体肝应激显著降低。减肥手术后，总细胞外囊泡数量减少。减肥手术后，通过 AnnexinV 和 AnnexinV 亚组鉴定的 HepPar1 或唾液酸糖蛋白受体 (ASGPR) 阳性的肝特异性囊泡均显著减少。分析循环肝特异性 mRNAs 时，我们发现尽管总循环 RNA 保持不变，但手术后这些 mRNAs 的水平降低。我们得出结论，在接受胃旁路手术的患者样本中可以检测到循环肝细胞外囊泡。这些囊泡在经典肝酶测量中观察到的肝应激降低后也减少了。我们得出结论，ASGPR 或 HepPar 阳性囊泡有可能作为肝特异性囊泡标志物。
