ILF3 is responsible for hyperlipidemia-induced arteriosclerotic calcification by mediating BMP2 and STAT1 transcription.

Abstract

Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

• Authors: Fei Xie, Qing-Ke Cui, Zhao-Yang Wang, Bin Liu, Wen Qiao, Na Li, Jie Cheng, Ya-Min Hou, Xin-Ying Dong, Ying Wang, Ming-Xiang Zhang
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 161 Pg. 39-52 (12 2021) ISSN: 1095-8584 [Electronic] England
• PMID: 34343541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Ltd.

Chemical References

• BMP2 protein, human
• Bone Morphogenetic Protein 2
• ILF3 protein, human
• Ilf3 protein, mouse
• Nuclear Factor 90 Proteins
• STAT1 Transcription Factor
• STAT1 protein, human

Topics

• Animals
• Arteriolosclerosis (etiology)
• Body Weight
• Bone Morphogenetic Protein 2 (genetics, metabolism)
• Gene Expression Regulation
• Humans
• Hyperlipidemias (genetics, metabolism, physiopathology)
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Muscle, Smooth, Vascular (metabolism, pathology)
• Nuclear Factor 90 Proteins (genetics, metabolism)
• Promoter Regions, Genetic
• STAT1 Transcription Factor (genetics, metabolism)
• Vascular Calcification (genetics, metabolism, physiopathology)