Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response
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 s...
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2022
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oai:doaj.org-article:b484a93dcc9d4ea2a8c2e5ba88baba0f2021-12-01T14:40:58ZAspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response1388-02091744-511610.1080/13880209.2021.2007268https://doaj.org/article/b484a93dcc9d4ea2a8c2e5ba88baba0f2022-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.2007268https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context 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.Quanquan ShenQian ChenYang LiuXiang XueXiaogang ShenQiang HeGuokun WangFei HanTaylor & Francis Grouparticlevascular smooth muscle cellsheat shock protein 70heat shock protein 90heat shock transcription factor 1Therapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 60, Iss 1, Pp 17-24 (2022) |
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vascular smooth muscle cells heat shock protein 70 heat shock protein 90 heat shock transcription factor 1 Therapeutics. Pharmacology RM1-950 |
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vascular smooth muscle cells heat shock protein 70 heat shock protein 90 heat shock transcription factor 1 Therapeutics. Pharmacology RM1-950 Quanquan Shen Qian Chen Yang Liu Xiang Xue Xiaogang Shen Qiang He Guokun Wang Fei Han Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
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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. |
format |
article |
author |
Quanquan Shen Qian Chen Yang Liu Xiang Xue Xiaogang Shen Qiang He Guokun Wang Fei Han |
author_facet |
Quanquan Shen Qian Chen Yang Liu Xiang Xue Xiaogang Shen Qiang He Guokun Wang Fei Han |
author_sort |
Quanquan Shen |
title |
Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
title_short |
Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
title_full |
Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
title_fullStr |
Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
title_full_unstemmed |
Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
title_sort |
aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response |
publisher |
Taylor & Francis Group |
publishDate |
2022 |
url |
https://doaj.org/article/b484a93dcc9d4ea2a8c2e5ba88baba0f |
work_keys_str_mv |
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