Hydrogen sulfide improves ox‑LDL‑induced expression levels of Lp‑PLA<sub>2</sub> in THP‑1 monocytes via the p38MAPK pathway

Hu,Heng-Jing; Qiu,Jie; Zhang,Chi; Tang,Zhi-Han; Qu,Shun-Lin; Jiang,Zhi-Sheng

doi:10.3892/mmr.2021.11997

Hydrogen sulfide improves ox‑LDL‑induced expression levels of Lp‑PLA₂ in THP‑1 monocytes via the p38MAPK pathway

Authors:
- Heng-Jing Hu
- Jie Qiu
- Chi Zhang
- Zhi-Han Tang
- Shun-Lin Qu
- Zhi-Sheng Jiang
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Affiliations: Department of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Cardiology Laboratory, Huazhong University of Science and Technology Tongji Medical College First Clinical College, Wuhan, Hubei 430000, P.R. China, Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: March 12, 2021 https://doi.org/10.3892/mmr.2021.11997
Article Number: 358
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hydrogen sulfide (H₂S) exerts an anti‑atherosclerotic effect and decreases foam cell formation. Lipoprotein‑associated phospholipase A2 (Lp‑PLA₂) is a key factor involved in foam cell formation. However, the association between H₂S and Lp‑PLA₂ expression levels with respect to foam cell formation has not yet been elucidated. The present study investigated whether H₂S can affect foam cell formation and potential signalling pathways via regulation of the expression and activity of Lp‑PLA₂. Using human monocytic THP‑1 cells as a model system, it was observed that oxidized low‑density lipoprotein (ox‑LDL) not only upregulates the expression level and activity of Lp‑PLA₂, it also downregulates the expression level and activity of Cystathionine γ lyase. Exogenous supplementation of H₂S decreased the expression and activity of Lp‑PLA₂ induced by ox‑LDL. Moreover, ox‑LDL induced the expression level and activity of Lp‑PLA₂ via activation of the p38MAPK signalling pathway. H₂S blocked the expression levels and activity of Lp‑PLA₂ induced by ox‑LDL via inhibition of the p38MAPK signalling pathway. Furthermore, H₂S inhibited Lp‑PLA₂ activity by blocking the p38MAPK signaling pathway and significantly decreased lipid accumulation in ox‑LDL‑induced macrophages, as detected by Oil Red O staining. The results of the present study indicated that H₂S inhibited ox‑LDL‑induced Lp‑PLA₂ expression levels and activity by blocking the p38MAPK signalling pathway, thereby improving foam cell formation. These findings may provide novel insights into the role of H₂S intervention in the progression of atherosclerosis.

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