Department of General Medicine, The Affiliated Hospital, College of Medicine, Qingdao University, Qingdao, China.
School of Basic Medical Sciences, College of Medicine, Qingdao University, Qingdao, China.
J Diabetes. 2023 Dec;15(12):1070-1080. doi: 10.1111/1753-0407.13457. Epub 2023 Aug 18.
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.
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.
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.
糖尿病性心肌病是糖尿病患者死亡的主要原因,而高血糖以外的因素导致糖尿病性心肌病发展的机制尚不清楚。血清小细胞外囊泡(sEVs)携带生物活性蛋白或核,进入远程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。本研究旨在探讨心血管疾病糖尿病患者 sEVs 中脂质的变化,希望为了解脂质代谢在糖尿病性心肌病发病机制中的作用提供新的思路。
使用来自健康对照者(Ctrl)、无心血管疾病的糖尿病患者(DM)和有心血管疾病的糖尿病患者(DM-CAD)血清的 sEVs 样本进行脂质组学分析。由于 AC16 细胞也用这些 sEVs 处理,以确认细胞进入和对胰岛素敏感性的影响,因此对细胞也进行了脂质组学分析。
在这项研究中,我们发现 DM-CAD 患者血清中 sEVs 的二十二碳六烯酸(DHA)-三酰甘油显著减少,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 sEVs 处理的细胞中 DHA-三酰甘油也减少。因此,sEVs 携带的 DHA-三酰甘油可能介导细胞间信号传递,并与糖尿病心血管并发症的发生有关。