Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease.
Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease.
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白脂素在糖尿病下肢外周动脉疾病中诱导血管内皮向间质转化。
DOI：
10.1186/s12933-022-01457-0
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发表时间：
2022-02-15
影响因子：
9.3
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
You M;Liu Y;Wang B;Li L;Zhang H;He H;Zhou Q;Cao T;Wang L;Zhao Z;Zhu Z;Gao P;Yan Z
功能失调的脂肪组织中脂肪因子分泌的改变促进了动脉粥样硬化疾病的发展，包括下肢外周动脉疾病（PAD）。 Asprosin 是最近发现的一种脂肪因子，在代谢中显示出有效的调节作用，但 Asprosin 与下肢 PAD 之间的关系尚未得到研究。招募33例2型糖尿病（T2DM）患者（DM）、51例T2DM合并PAD患者（DM + PAD）和30例健康正常对照（NC）志愿者，采集血样用于检测循环白脂素水平和代谢组学筛查。使用 2 型糖尿病 db/db 小鼠的主动脉组织进行 RNA 测序，并用白脂素处理人脐静脉内皮细胞 (HUVEC)，以确定其对内皮间质转化 (EndMT) 的影响。 DM + PAD组白脂素循环水平显着高于NC组和DM组。即使在调整了年龄、性别、体重指数 (BMI) 和其他 PAD 传统危险因素后，循环白脂素水平仍与踝臂指数 (ABI) 显着负相关。 Logistic回归分析显示，白脂素是PAD的独立危险因素，受试者操作特征（ROC）曲线确定了白脂素区分PAD的良好敏感性（74.5%）和特异性（74.6%）。代谢组学数据显示，PAD 患者肌成纤维细胞产生胶原蛋白时氨基酸从头合成的典型特征，并且 db/db 小鼠主动脉组织中出现 TGF-β 信号通路激活。 Asprosin 以 TGF-β 依赖性方式直接诱导 HUVEC 中的 EndMT，因为 TGF-β 信号通路抑制剂 SB431542 消除了 Asprosin 对 EndMT 的促进作用。循环白脂素水平升高是下肢 PAD 的独立危险因素，可作为诊断标志物。从机制上讲，Asprosin 直接诱导 EndMT，通过激活 TGF-β 信号通路参与血管损伤。试验注册 该试验在 ClinicalTrials.gov 上注册为 NCT05068895。在线版本包含可在 10.1186/s12933-022-01457-0 获取的补充材料。
Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated. 33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM + PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT). The circulating levels of asprosin in DM + PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD. Logistic regression analysis revealed that asprosin is an independent risk factor for PAD and receiver-operator characteristic (ROC) curve determined a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD. Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in patients with PAD and activation of TGF-β signaling pathway appeared in the aortic tissue of db/db mice. Asprosin directly induces EndMT in HUVECs in a TGF-β-dependent manner as TGF-β signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT. Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-β signaling pathway. Trial registration This trial was registered at clinicaltrials.gov as NCT05068895 The online version contains supplementary material available at 10.1186/s12933-022-01457-0.
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DOI：
10.1161/atvbaha.112.301089
发表时间：
2013-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Joosten MM;Joshipura KJ;Pai JK;Bertoia ML;Rimm EB;Mittleman MA;Mukamal KJ
通讯作者：
Mukamal KJ
甘油三酯-葡萄糖指数在外周动脉疾病发展中的作用：社区动脉粥样硬化风险 (ARIC) 研究的结果
影响因子：
9.3
作者：
Gao JW;Hao QY;Gao M;Zhang K;Li XZ;Wang JF;Vuitton DA;Zhang SL;Liu PM
通讯作者：
Liu PM
内皮 TGF-β 信号传导驱动血管炎症和动脉粥样硬化
影响因子：
20.8
作者：
Chen, Pei-Yu;Qin, Lingfeng;Simons, Michael
通讯作者：
Simons, Michael
DOI：
10.3390/diagnostics10090723
发表时间：
2020-09-20
期刊：
Diagnostics (Basel, Switzerland)
影响因子：
--
作者：
Ceasovschih A;Sorodoc V;Onofrei Aursulesei V;Tesloianu D;Tuchilus C;Anisie E;Petris A;Statescu C;Jaba E;Stoica A;Grigorescu ED;Jaba IM;Sorodoc L
通讯作者：
Sorodoc L
影响因子：
8.3
作者：
Cipollone, F;Fazia, M;Porreca, E
通讯作者：
Porreca, E