Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes.
Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes.
复制标题
DOI：
10.1136/bmjdrc-2021-002579
复制
发表时间：
2022-01
影响因子：
4.1
通讯作者：
Zou M
中科院分区：
文献类型：
--
作者：
Ding X;Meng C;Dong H;Zhang S;Zhou H;Tan W;Huang L;He A;Li J;Huang J;Li W;Zou F;Zou M
动脉粥样硬化是糖尿病血管病变的主要病理改变，血管炎症在早期动脉粥样硬化中起重要作用。细胞外热休克蛋白90（eHsp90）是一种分泌到血清中的蛋白质，参与多种生理和病理生理过程。然而，eHsp90在早期动脉粥样硬化中的具体机制尚不清楚。本研究旨在探讨热休克蛋白90（Hsp90）与糖尿病下肢动脉病变的关系，探讨环境刺激下血管内皮细胞eHsp90的表达及eHsp90α在糖尿病动脉粥样硬化中的作用和机制。入选患者103例，分为糖尿病组（n=27）、糖尿病下肢动脉病变组（n=46）和糖尿病严重肢体缺血组（n=30）。分析血清热休克蛋白90、氧化应激指标与患者预后的关系及各指标之间的相关性。应用H&E染色和免疫组织化学方法观察糖尿病足患者离断足血管的分布。建立高糖条件下氧化应激内皮损伤模型，探讨eHsp90释放在动脉粥样硬化进展中的作用。血清Hsp90水平随糖尿病血管病变的加重而升高。Hsp90α与丙二醛有一定的相关性，是糖尿病血管病变进展的独立危险因素，具有预测能力。热休克蛋白90 α的表达面积与管腔内炎性浸润面积一致。血管内皮细胞在应激状态下分泌eHsp90α增加。抑制eHsp90α可以减轻细胞炎症和损伤程度。内皮细胞条件培养液和重组人热休克蛋白90 α通过低密度脂蛋白受体相关蛋白1（LRP 1）受体增加单核细胞迁移，促进疾病进展。eHsp90α在动脉粥样硬化的早期炎症损伤阶段起着重要作用。NCT 04787770。
Atherosclerosis is the main pathological change in diabetic angiopathy, and vascular inflammation plays an important role in early atherosclerosis. Extracellular heat shock protein 90 (eHsp90) is secreted into the serum and is involved in various physiological and pathophysiological processes. However, the specific mechanism of eHsp90 in early atherosclerosis remains unclear. This study explored the relationship between Hsp90 and diabetic lower extremity arterial disease and investigated the expression of eHsp90 in vascular endothelial cells under environmental stimulation and the function and mechanism of eHsp90α involved in diabetic atherosclerosis. One hundred and three selected patients were divided into three groups: the diabetes mellitus group (n=27), the diabetic lower extremity arterial disease group (n=46), and the diabetic critical limb ischemia group (n=30). The relationships among serum Hsp90, oxidative stress indexes, and patient outcomes and the correlations among the indexes were analyzed. H&E staining and immunohistochemistry were used to observe the vasculature of amputated feet from patients with diabetic foot. An oxidative stress endothelial injury model was established under high glucose in vitro to explore the role of eHsp90 release in atherosclerosis progression. The level of serum Hsp90 was upregulated with aggravation of diabetic vascular disease. Hsp90α was correlated with malondialdehyde to some extent and was an independent risk factor in the progression of diabetic vascular disease, with predictive ability. The expression area of Hsp90α was consistent with the area of inflammatory infiltration in the vessel lumen. Vascular endothelial cells were found to increase eHsp90α secretion under stress. Then inhibition of eHsp90α can reduce the degree of cellular inflammation and damage. Endothelial cell-conditioned medium and recombinant human Hsp90α increased monocyte migration via the low-denisity lipoprotein receptor-related protein 1 (LRP1) receptor to promote disease progression. eHsp90α plays a critical role in the early inflammatory injury stage of atherosclerosis. NCT04787770.
登录
查看更多内容
影响因子：
--
作者：
Profumo E;Buttari B;Tinaburri L;D'Arcangelo D;Sorice M;Capozzi A;Garofalo T;Facchiano A;Businaro R;Kumar P;Singh BK;Parmar VS;Saso L;Riganò R
通讯作者：
Riganò R
影响因子：
0.7
作者：
Mudau M;Genis A;Lochner A;Strijdom H
通讯作者：
Strijdom H
氧化的低密度脂蛋白（OXLDL）处理的树突状细胞促进了人类动脉粥样硬化斑块和血液中T细胞的激活，这被汀类药物抑制：MicroRNA let-7c是该作用不可或缺的。
影响因子：
5.4
作者：
Frostegård J;Zhang Y;Sun J;Yan K;Liu A
通讯作者：
Liu A
影响因子：
20.1
作者：
Lei, HT;Romeo, G;Kazlauskas, A
通讯作者：
Kazlauskas, A
影响因子：
7.7
作者：
Lazaro, Iolanda;Oguiza, Ainhoa;Gomez-Guerrero, Carmen
通讯作者：
Gomez-Guerrero, Carmen