Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response.
Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response.
复制标题
阿司匹林通过增强热休克反应减轻主动脉平滑肌细胞的钙化
DOI：
10.1080/13880209.2021.2007268
复制
发表时间：
2022-12
影响因子：
3.8
通讯作者：
Han F
中科院分区：
文献类型：
--
作者：
Shen Q;Chen Q;Liu Y;Xue X;Shen X;He Q;Wang G;Han F
摘要血管钙化是慢性肾功能衰竭的主要并发症之一，它是由血管平滑肌细胞（VSMCs）成骨转化驱动的一个活跃过程。阿司匹林可通过诱导热休克反应而减轻心肌细胞损伤。目的探讨阿司匹林对血管平滑肌细胞钙化的影响。材料与方法采用成骨培养液诱导血管平滑肌细胞钙化10天，建立体外钙化模型。将VSMCs分为对照组（正常培养液）、钙化组（成骨培养液）和治疗组（成骨培养液中加入1或4 mmol/L阿司匹林）。通过钙化结节形成、细胞内钙浓度和成骨细胞标志物（OPN和Runx 2）表达评价VSMC钙化。结果培养10天后，钙化组细胞内钙离子浓度明显高于对照组（1.16 ± 0.04vs0.14 ± 0.01 μg/mg，p < 0.01），但1 mmol/L阿司匹林组显著降低4 mmol/L阿司匹林组（0.93 ± 0.03 μg/mg，p < 0.01）。1或4 mmol/L阿司匹林可明显抑制成骨培养液诱导的骨桥蛋白和Runx 2的表达。钙化组HSF 1、HSP 70和HSP 90表达明显降低，阿司匹林治疗组表达明显升高。小分子抑制剂或小干扰RNA抑制HSP 70（或HSP 90）可部分阻断阿司匹林的抗钙化作用，细胞内钙离子浓度和成骨细胞标志物表达的变化证实了这一点。讨论和结论阿司匹林可部分通过HSP 70或HSP 90介导的热休克反应减轻血管平滑肌细胞的钙化。这些发现扩展了对阿司匹林药理学的理解，并意味着局部诱导热休克蛋白表达可能是预防和治疗血管钙化的潜在治疗策略。
Abstract Context Vascular calcification is a major complication of chronic renal failure, which has been identified as an active process partly driven by osteogenic transition of vascular smooth muscle cells (VSMCs). Aspirin could prevent cardiomyocyte damage by inducing heat shock response. Objective This study investigates the effect of aspirin on alleviating VSMC calcification. Materials and methods An in vitro VSMC calcification model was established by 10-day calcification induction in osteogenic medium. VSMCs were grouped as following: control group (normal medium), calcified group (osteogenic medium) and treated group (osteogenic medium with 1 or 4 mmol/L aspirin). VSMC calcification was evaluated by calcified nodules formation, intracellular calcium concentration and osteoblastic marker (OPN and Runx2) expression. Results After 10-day culture, the intracellular calcium concentration in calcified group was significantly higher than that in control group (1.16 ± 0.04 vs. 0.14 ± 0.01 μg/mg, p < 0.01), but significantly reduced in 1 mmol/L aspirin treated group (0.74 ± 0.05 μg/mg, p < 0.01), and 4 mmol/L aspirin treated group (0.93 ± 0.03 μg/mg, p < 0.01). The elevated expression of OPN and Runx2 induced by osteogenic medium was significantly relieved after 1 or 4 mmol/L aspirin treatment. The expression of HSF1, HSP70 and HSP90 was decreased in calcification-induced VSMCs, but significantly increased after treatment of aspirin. Furthermore, inhibition of HSP70 (or HSP90) by small-molecule inhibitor or small interfering RNA could partially abolish the anti-calcification effect of aspirin, proved by the changes of intracellular calcium concentration and osteoblastic marker expression. Discussion and conclusions Aspirin could relieve the calcification of VSMCs partially through HSP70- or HSP90-mediated heat shock response. These findings expanded the understanding of aspirin pharmacology, and imply that local induction expression of HSPs might be a potential therapeutic strategy for the prevention and therapy of vascular calcification.
登录
查看更多内容
影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
通讯作者：
Shanahan CM
DOI：
10.1126/science.1215327
发表时间：
2012-05-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hawley SA;Fullerton MD;Ross FA;Schertzer JD;Chevtzoff C;Walker KJ;Peggie MW;Zibrova D;Green KA;Mustard KJ;Kemp BE;Sakamoto K;Steinberg GR;Hardie DG
通讯作者：
Hardie DG
DOI：
10.1007/978-3-319-43589-3_13
发表时间：
2016-01-01
期刊：
AMP-ACTIVATED PROTEIN KINASE
影响因子：
--
作者：
Guigas, Bruno;Viollet, Benoit
通讯作者：
Viollet, Benoit
影响因子：
5.7
作者：
Scharf, Ruediger E.
通讯作者：
Scharf, Ruediger E.
影响因子：
158.5
作者：
Weitz, J. I.;Lensing, A. W. A.;Prandoni, P.
通讯作者：
Prandoni, P.