Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome.
Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome.
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DOI：
10.14814/phy2.15530
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发表时间：
2023-01
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
--
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代谢综合征（MetS）增加心血管疾病的风险。细胞外囊泡（EVs）已成为胰岛素敏感性的重要介质，尽管很少有关于人体血管功能的研究。我们确定了胰岛素对EV与血管功能的关系。MetS成人（n = 51，n = 9 M，54.8 ± 1.0岁，36.4 ± 0.7 kg/m2，ATP III：3.5 ± 0.1 a.u.，VO 2 max：22.1 ± 0.6 ml/kg/min）入组本横断面研究。在正葡萄糖钳夹（40 mU/m2/min，90 mg/dl）期间测定外周胰岛素敏感性（M值），并采集EV（CD 105+、CD 45+、CD 41+、TX+和CD 31 +;光谱流式细胞术）、炎症、胰岛素和底物的血液。通过主动脉波形在0和120分钟时测定中心血流动力学（压平眼压计）。使用压力肌描记术评估在0.2、2和20 nM胰岛素下，来自健康和MetS成人EV的小鼠三级肠系膜动脉（直径100-200 μm）的胰岛素诱导的动脉血管舒张。患有MetS的成人具有低外周胰岛素敏感性（2.6 ± 0.2 mg/kg/min）和高HOMA-IR（4.7 ± 0.4 a.u.）加脂肪-IR（13.0 ± 1.3 a.u.）。胰岛素降低总/颗粒计数（p < 0.001）、CD 45 + EV（p = 0.002）、AIx 75（p = 0.005）和Pb（p = 0.04）、FFA（p < 0.001）、总脂联素（p = 0.006）、ICAM（p = 0.002）和VCAM（p = 0.03）。较高的M值与较低的空腹总EV相关（r =-0.40，p = 0.004），而较高的脂肪IR与较高的空腹EV相关（r = 0.42，p = 0.004），与VAT无关。CD 105+和CD 45+来源的总EV与空腹AIx 75（r = 0.29，p < 0.05）和Pb（r = 0.30，p < 0.05）相关。与不同胰岛素剂量的健康对照相比，MetS参与者的EV减弱了肠系膜动脉中胰岛素诱导的血管舒张（所有p < 0.005）。这些数据突出了EV作为血管胰岛素敏感性和疾病风险的潜在新型介质。本研究探讨了胰岛素对细胞外囊泡（EV）的影响与血管胰岛素敏感性的成年人代谢综合征。我们的数据表明，胰岛素输注减少了EV的亚型，并降低了主动脉波形。使用压力肌电图，我们还显示，与健康对照组相比，MetS参与者的富集EV制剂减弱了胰岛素的血管舒张作用。因此，EV似乎是血管胰岛素敏感性的重要调节剂。
Metabolic Syndrome (MetS) raises cardiovascular disease risk. Extracellular vesicles (EVs) have emerged as important mediators of insulin sensitivity, although few studies on vascular function exist in humans. We determined the effect of insulin on EVs in relation to vascular function. Adults with MetS (n = 51, n = 9 M, 54.8 ± 1.0 years, 36.4 ± 0.7 kg/m2, ATPIII: 3.5 ± 0.1 a.u., VO2max: 22.1 ± 0.6 ml/kg/min) were enrolled in this cross‐sectional study. Peripheral insulin sensitivity (M‐value) was determined during a euglycemic clamp (40 mU/m2/min, 90 mg/dl), and blood was collected for EVs (CD105+, CD45+, CD41+, TX+, and CD31+; spectral flow cytometry), inflammation, insulin, and substrates. Central hemodynamics (applanation tonometry) was determined at 0 and 120 min via aortic waveforms. Pressure myography was used to assess insulin‐induced arterial vasodilation from mouse 3rd order mesenteric arteries (100–200 μm in diameter) at 0.2, 2 and 20 nM of insulin with EVs from healthy and MetS adults. Adults with MetS had low peripheral insulin sensitivity (2.6 ± 0.2 mg/kg/min) and high HOMA‐IR (4.7 ± 0.4 a.u.) plus Adipose‐IR (13.0 ± 1.3 a.u.). Insulin decreased total/particle counts (p < 0.001), CD45+ EVs (p = 0.002), AIx75 (p = 0.005) and Pb (p = 0.04), FFA (p < 0.001), total adiponectin (p = 0.006), ICAM (p = 0.002), and VCAM (p = 0.03). Higher M‐value related to lower fasted total EVs (r = −0.40, p = 0.004) while higher Adipose‐IR associated with higher fasted EVs (r = 0.42, p = 0.004) independent of VAT. Fasting CD105+ and CD45+ derived total EVs correlated with fasting AIx75 (r = 0.29, p < 0.05) and Pb (r = 0.30, p < 0.05). EVs from MetS participants blunted insulin‐induced vasodilation in mesenteric arteries compared with increases from healthy controls across insulin doses (all p < 0.005). These data highlight EVs as potentially novel mediators of vascular insulin sensitivity and disease risk. This study investigates the effects of insulin on extracellular vesicles (EVs) in relation to vascular insulin sensitivity in adults with MetS. Our data suggest that insulin infusion decreases subtypes of EVs and lowers aortic waveforms. Using pressure myography, we also show enriched EVs preps from MetS participants blunt the vasodilatory effect of insulin compared with increases from healthy controls. Thus, EVs appear to be important modifiers of vascular insulin sensitivity.
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影响因子：
29
作者：
Isaac R;Reis FCG;Ying W;Olefsky JM
通讯作者：
Olefsky JM
影响因子：
4.3
作者：
Eichner NZM;Erdbrügger U;Malin SK
通讯作者：
Malin SK
影响因子：
5.9
作者：
Eichner, Natalie Z. M.;Gilbertson, Nicole M.;Malin, Steven K.
通讯作者：
Malin, Steven K.
DOI：
10.1007/s003920050461
发表时间：
2000-03-01
期刊：
ZEITSCHRIFT FUR KARDIOLOGIE
影响因子：
--
作者：
Becker, BF;Heindl, B;Zahler, S
通讯作者：
Zahler, S
影响因子：
8.3
作者：
Good, Miranda E.;Musante, Luca;Erdbruegger, Uta
通讯作者：
Erdbruegger, Uta