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IFIT2 mediates iron retention and cholesterol efflux in atherosclerosis.
Chen, Haoqiang; Wu, Haiyan; Wang, Qian; Zhang, Hong.
Afiliación
  • Chen H; Department of Cardiovascular Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming, Yunnan 650032, P.R.China.
  • Wu H; Department of Cardiovascular Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming, Yunnan 650032, P.R.China; Faculty of Life Science and Technology, Kunming University of Science and Technology,
  • Wang Q; Department of Cardiovascular Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming, Yunnan 650032, P.R.China. Electronic address: 85891990@qq.com.
  • Zhang H; Department of Cardiovascular Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming, Yunnan 650032, P.R.China. Electronic address: zhanghong@kust.edu.cn.
Int Immunopharmacol ; 142(Pt A): 113131, 2024 Dec 05.
Article en En | MEDLINE | ID: mdl-39276454
ABSTRACT

BACKGROUND:

Abnormalities in iron and lipid metabolism are recognized as key contributors to atherosclerosis (AS). Therefore, this study proposes to characterize the biomarker related to iron and lipid metabolism in AS using bioinformatics, animal, and cell experiments.

METHODS:

The limma package was utilized to identify differentially expressed genes (DEGs) in GSE70126 and GSE70619 datasets, and biomarkers were screened using enrichment analysis and PPI networks. IFIT2 was knocked down using shRNA lentivirus in a high fat diet (HFD)-induced APOE-/- AS model to investigate its effects of IFIT2 on the pathology, iron retention, and lipid accumulation. Iron storage-related and cholesterol efflux-related proteins were evaluated following exogenous modulation of IFIT2 expression in ox-LDL-induced foamy macrophages.

RESULTS:

Compared to non-foamy macrophages from the aorta, 189 and 4152 DEGs were identified in foamy macrophages within the GSE70126 and GSE70619 datasets, respectively. Moreover, intersecting DEGs may modulate immune responses, cell adhesion, vascular permeability, and oxidative stress through NF-kappa B, Wnt, TNF and HIF-1 signaling pathways. Notably, IFIT2 was significantly upregulated in foamy macrophages and AS models. In vivo, IFIT2 co-localized with foamy macrophages, and its knockdown led to reductions in plasma lipid levels, plaque area, immune infiltration, iron retention, and lipid accumulation. In vitro, IFIT2 knockdown alleviated the ox-LDL-induced increase in iron storage-related proteins (Ferritin-L and Ferritin-H) and iron (Fe2+ and Fe3+) in foamy macrophages. Furthermore, IFIT2 knockdown reduced lipid accumulation and upregulated cholesterol efflux-related proteins (PPARγ, LXRα, ABCA1, and ABCG1) in foamy macrophages.

CONCLUSION:

IFIT2 knockdown attenuates iron retention and lipid accumulation in AS plaques, and facilitated cholesterol efflux from foamy macrophages via the PPARγ/LXRα/ABCA1-ABCG1 pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colesterol / Aterosclerosis / Hierro Límite: Animals / Humans / Male Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colesterol / Aterosclerosis / Hierro Límite: Animals / Humans / Male Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos