Effects of circulating endothelial microvesicles isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide production.
Effects of circulating endothelial microvesicles isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide production.
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从肥胖成人中分离的循环内皮微泡对内皮细胞炎症、细胞凋亡和一氧化氮产生的影响。
DOI：
10.1152/ajpendo.00139.2023
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
DeSouza,ChristopherA
中科院分区：
文献类型：
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作者：
Garcia,ViniciusP;Fandl,HannahK;Hijmans,JamieG;Berry,AuburnR;Cardenas,HannahL;Stockelman,KellyA;DeSouza,NoahM;Treuth,JWilliam;Greiner,JaredJ;Park,AndrewJ;Stauffer,BrianL;DeSouza,ChristopherA
循环内皮细胞来源的微囊泡(EMVS)已被证明随着肥胖而增加，并与内皮功能障碍相关；然而，它们对内皮细胞的直接影响尚不清楚。本研究的实验目的是确定从肥胖成人分离的EMVS对内皮细胞炎症、凋亡和一氧化氮(NO)产生的影响。用流式细胞仪对12例久坐不动的成人血浆中CD144+微泡进行鉴定、计数和分离，其中正常体重成人12例[男性8例；年龄55 ± 6岁；体质量指数：24.3 ± 0.7 kg/m2；EMV：144 ± 53EMVS/µL]；肥胖者12例(6 M/6女性；59 ± 7岁；BMI：31.0 ± 1.1 kg/m2；EMV245 ± 89EMVS/L)。培养人脐静脉内皮细胞，并用来自正常体重成人和肥胖成人的EMVS处理。与正常体重成人内皮细胞相比，肥胖成人内皮细胞分泌IL-6(108.2 ± 7.7vs.90.9 ± 10.0pg/mL)和IL-8(75.4 ± 9.8vs.59.5pg/mlvs.59.5 ± 11.5pg/mL)显著增加，这与细胞内磷酸化的核因子-κB p65(Ser536；激活的NF-κB)表达增加[145.0 ± 341vs.114.5 ± 30.4任意单位(AU)]一致。在肥胖相关EMVS处理的细胞中，磷酸化p38-MAPK(15.4 ± 5.7AU比9.2 ± 2.5AU)和活性caspase-3(168.2 ± 65.5AU比107.8 ± 40.5AU)的表达更高。肥胖组eNOS(Ser1177)表达(2 3.5 ± 7.2比34.7 ± 9.7AU)和NO生成量(6.9 ± 1.4vs.8.7 ± 0.7µm ol/L)显著降低。这些数据表明，来自肥胖成人的循环EMV促进了促炎症、促凋亡和无损害的内皮表型。循环内皮细胞是肥胖相关内皮功能障碍的潜在介质。在本研究中，我们检测了从肥胖成人中分离的循环内皮细胞衍生微囊(EMV)在体外对内皮细胞炎症、凋亡和一氧化氮(NO)产生的影响。从肥胖成人采集的循环内皮细胞促进促炎、促凋亡和无损害的内皮表型。肥胖成人的循环EMVS升高，独立于其他心脏代谢危险因素，是肥胖相关血管内皮功能障碍和血管风险的潜在的新的全身性介质。
Circulating endothelial cell-derived microvesicles (EMVs) have been shown to be elevated with obesity and associated with endothelial dysfunction; however, their direct effect on endothelial cells is unknown. The experimental aim of this study was to determine the effect of EMVs isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide (NO) production. EMVs (CD144+ microvesicles) were identified, enumerated, and isolated from plasma by flow cytometry from 24 sedentary adults: 12 normal-weight adults [8 M/4 F; age: 55 ± 6 yr; body mass index (BMI): 24.3 ± 0.7 kg/m2; EMV: 144 ± 53 EMVs/µL] and 12 adults with obesity (6 M/6 F; 59 ± 7 yr; BMI: 31.0 ± 1.1 kg/m2; EMV: 245 ± 89 EMVs/µL). Human umbilical vein endothelial cells were cultured and treated with EMVs from either normal-weight adults or adults with obesity. EMVs from obese adults induced significantly higher release of interleukin (IL)-6 (108.2 ± 7.7 vs. 90.9 ± 10.0 pg/mL) and IL-8 (75.4 ± 9.8 vs. 59.5 ± 11.5 pg/mL) from endothelial cells vs. EMVs from normal-weight adults, concordant with greater intracellular expression of phosphorylated NF-κB p65 (Ser536; active NF-κB) [145.0 ± 34.1 vs. 114.5 ± 30.4 arbitrary units (AU)]. Expression of phosphorylated p38-MAPK (15.4 ± 5.7 vs. 9.2 ± 2.5 AU) and active caspase-3 (168.2 ± 65.5 vs. 107.8 ± 40.5 AU), markers of cell apoptosis, was higher in cells treated with obesity-related EMVs. Phosphorylated endothelial nitric oxide synthase (eNOS) (Ser1177) expression (23.5 ± 7.2 vs. 34.7 ± 9.7 AU) and NO production (6.9 ± 1.4 vs. 8.7 ± 0.7 µmol/L) were significantly lower in the cells treated with EMVs from obese adults. These data indicate that circulating EMVs from adults with obesity promote a proinflammatory, proapoptotic, and NO-compromised endothelial phenotype. Circulating EMVs are a potential mediator of obesity-related endothelial dysfunction.NEW & NOTEWORTHYIn the present study, we determined the effect of circulating endothelial cell-derived microvesicles (EMVs) isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide (NO) production in vitro. Circulating EMVs harvested from adults with obesity promoted a proinflammatory, proapoptotic, and NO-compromised endothelial phenotype. Elevated circulating EMVs in adults with obesity, independent of other cardiometabolic risk factors, are a potential novel systemic mediator of obesity-related endothelial dysfunction and vascular risk.