ArticleArteriosclerosis, thrombosis, and vascular biology2018
Transcription Factor Zhx2 Deficiency Reduces Atherosclerosis and Promotes Macrophage Apoptosis in Mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- NAD Metabolism Regulates Proliferation of Macrophages in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease.BMC nephrology · 2025Article
- The Regulatory Network of Transcription Factors in Macrophage Polarization.ImmunoTargets and therapy · 2025Review
- Article
- GATA2‑miR‑374a axis promotes vascular smooth muscle cells proliferation, migration via targeting circTADA2A/RORA axis.Experimental and therapeutic medicine · 2024Article
- The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases.Frontiers in cardiovascular medicine · 2024Review
- Article
- Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.Cell death and differentiation · 2023Article
- Article
- Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.JCI insight · 2023Article
- Macrophages in aseptic loosening: Characteristics, functions, and mechanisms.Frontiers in immunology · 2023Review
- Zinc fingers and homeoboxes 2 is required for diethylnitrosamine-induced liver tumor formation in C57BL/6 mice.Hepatology communications · 2022Article
- Novel Biomarkers of Atherosclerotic Vascular Disease-Latest Insights in the Research Field.International journal of molecular sciences · 2022Review
- ZHX2 in health and disease.Frontiers in oncology · 2022Review
- ATF4 promotes brain vascular smooth muscle cells proliferation, invasion and migration by targeting miR-552-SKI axis.PloS one · 2022Article
- Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity.The Journal of experimental medicine · 2021Article
- Roles of Macrophages in Atherogenesis.Frontiers in pharmacology · 2021Review
- Identification of Key Pathways and Genes in Obesity Using Bioinformatics Analysis and Molecular Docking Studies.Frontiers in endocrinology · 2021Article
- Local M-CSF (Macrophage Colony-Stimulating Factor) Expression Regulates Macrophage Proliferation and Apoptosis in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Objective- The objective of this study was to determine the basis of resistance to atherosclerosis of inbred mouse strain BALB/cJ. Approach and Results- BALB/cJ mice carry a naturally occurring null mutation of the gene encoding the transcription factor Zhx2, and genetic analyses suggested that this may confer resistance to atherosclerosis. On a hyperlipidemic low-density lipoprotein receptor null background, BALB/cJ mice carrying the mutant allele for Zhx2 exhibited up to a 10-fold reduction in lesion size as compared with an isogenic strain carrying the wild-type allele. Several lines of evidence, including bone marrow transplantation studies, indicate that this effect of Zhx2 is mediated, in part, by monocytes/macrophages although nonbone marrow-derived pathways are clearly involved as well. Both in culture and in atherosclerotic lesions, macrophages from Zhx2 null mice exhibited substantially increased apoptosis. Zhx2 null macrophages were also enriched for M2 markers. Effects of Zhx2 on proliferation and other bone marrow-derived cells, such as lymphocytes, were at most modest. Expression microarray analyses identified >1000 differentially expressed transcripts between Zhx2 wild-type and null macrophages. To identify the global targets of Zhx2, we performed ChIP-seq (chromatin immunoprecipitation sequencing) studies with the macrophage cell line RAW264.7. The ChIP-seq peaks overlapped significantly with gene expression and together suggested roles for transcriptional repression and apoptosis. Conclusions- A mutation of Zhx2 carried in BALB/cJ mice is responsible in large part for its relative resistance to atherosclerosis. Our results indicate that Zhx2 promotes macrophage survival and proinflammatory functions in atherosclerotic lesions, thereby contributing to lesion growth.
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