Decreased in n-3 DHA enriched triacylglycerol in small extracellular vesicles of diabetic patients with cardiac dysfunction

患有心脏功能障碍的糖尿病患者的细胞外小囊泡中富含 n-3 DHA 的三酰甘油减少

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作者:Wei Ding, Xuejuan Zhang, Dandan Xiao, Wenguang Chang

Conclusions

In this study, we found that docosahexaenoic acid (DHA)-triacylglycerides of sEVs from serums of DM-CAD patients decreased significantly, and those sEVs could enter into AC16 cells and diminish insulin sensitivity. In addition, DHA-triacylglycerides were also decreased in cells treated with sEVs from DM-CAD. Therefore, DHA-triacylglycerides carried by sEVs may mediate intercellular signaling and be associated with the incidence of diabetic cardiovascular complications. 背景:糖尿病心肌病是糖尿病患者死亡的主要原因,除高血糖外,其他因素导致糖尿病心肌病发展的机制尚不清楚。血清sEVs携带生物活性蛋白质或细胞核,进入远端组织并调节细胞功能。然而,在糖尿病条件下,sEVs携带的脂质变化尚未确定。我们的研究旨在探索心血管疾病糖尿病患者sEVs中脂质的变化,我们希望为理解脂质代谢在糖尿病心肌病发病机制中的作用提供新的思路 方法:对健康对照(Ctrl)、无心血管疾病的糖尿病患者(DM)和患有心血管疾病的糖尿病患者(DM-CAD)血清来源的SEVs样本进行脂质组学分析。以这些sEVs处理AC16细胞以确认其进入细胞和对胰岛素敏感性的影响,对细胞进行脂质组学分析 结果:本研究发现,DM-CAD患者血清中sEVs的DHA-三酰甘油显著降低,这些sEVs可以进入AC16细胞并降低胰岛素敏感性。此外,用DM-CAD患者血清中sEVs处理的细胞中DHA-三酰甘油也降低 结论:sEVs携带的DHA-三酰甘油可能介导细胞间信号传导,并与糖尿病心血管并发症的发生有关.

Methods

SEVs samples derived from serum of health controls (Ctrl), diabetic patients without cardiovascular diseases (DM), and diabetic patients with cardiovascular diseases (DM-CAD) were used for lipidomics analysis. Because AC16 cells are also treated with those sEVs to confirm the entrance of cells and effects on insulin sensitivity, a lipidomics analysis on cells was also performed.

Purpose

Diabetic cardiomyopathy is the leading cause of death in diabetic patients, and the mechanism by which factors other than hyperglycemia contribute to the development of diabetic cardiomyopathy is unknown. Serum small extracellular vesicles (sEVs) carry bioactive proteins or nuclei, which enter into remote tissues and modulate cell functions. However, in diabetic conditions, the changes of lipids carried by sEVs has not been identified. Our study aims to explore the changes of lipids in sEVs in diabetic patients with cardiovascular disease, we hope to provide new ideas for understanding the role of lipid metabolism in the pathogenesis of diabetic cardiomyopathy.

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