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Oxidized LDL induces vimentin secretion by macrophages and contributes to atherosclerotic inflammation
- Title
- Oxidized LDL induces vimentin secretion by macrophages and contributes to atherosclerotic inflammation
- Authors
- Kim, SeoYeon; Cho, Wonkyoung; Kim, Inyeong; Lee, Sang-Hak; Oh, Goo Taeg; Park, Young Mi
- Ewha Authors
- 오구택; 박영미; 조원경
- SCOPUS Author ID
- 오구택; 박영미; 조원경
- Issue Date
- 2020
- Journal Title
- JOURNAL OF MOLECULAR MEDICINE-JMM
- ISSN
- 0946-2716
1432-1440
- Citation
- JOURNAL OF MOLECULAR MEDICINE-JMM vol. 98, no. 7, pp. 973 - 983
- Keywords
- Vimentin; Oxidized LDL; Atherosclerosis; Intermediate filament; TNF-alpha; NF-kappa B signaling
- Publisher
- SPRINGER HEIDELBERG
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Activated macrophages show increased expression of vimentin, an intermediate filament protein. Macrophages secrete vimentin into extracellular space; however, the functions of extracellular vimentin and the process of vimentin secretion are not clearly defined. We found that oxidized low-density lipoproteins (oxLDL) via CD36 induced vimentin secretion in macrophages. We also revealed that extracellular vimentin induced macrophages to release inflammatory cytokines and augmented oxLDL-induced release of TNF-alpha and IL-6. Extracellular vimentin activated NF-kappa B signaling via phosphorylation of focal adhesion kinase (p-FAK) and I kappa B kinase (p-I kappa K). Extracellular vimentin also amplified the oxLDL-induced p-I kappa K increase and I kappa B decrease. Vimentin-induced TNF-alpha release was not dependent on Dectin-1, which is known to bind vimentin. We measured serum vimentin concentrations and found that patients with atherosclerotic coronary artery disease had higher levels of serum vimentin than normal subjects. Circulating oxLDL and vimentin concentrations showed a high degree of correlation. In mouse experiments, vimentin concentration was higher in the sera of apoE null mice with western diet-induced atherosclerosis than in the sera of chow diet-fed apoE null mice without atherosclerosis. We concluded that vimentin is secreted by oxLDL/CD36 interaction in macrophages and extracellular vimentin promotes macrophage release of pro-inflammatory cytokines. This may contribute to atherosclerotic inflammation and based on our analysis of serum vimentin, we suggest serum vimentin as a predictive marker for atherosclerosis. Key messages
- DOI
- 10.1007/s00109-020-01923-w
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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