Transcription Factor Zhx2 Deficiency Reduces Atherosclerosis and Promotes Macrophage Apoptosis in Mice

Arteriosclerosis, Thrombosis, and Vascular Biology
Ayca ErbilginAldons J Lusis

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 g...Continue Reading

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Citations

Dec 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Mar 18, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zehua WangChunhong Ma
Mar 28, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Congqing WuHong S Lu
Aug 23, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Fang LiHanrui Zhang
Oct 23, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Satyesh K SinhaAldons J Lusis
Jul 20, 2021·The Journal of Experimental Medicine·Siyu TanChunhong Ma
Aug 1, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Zi-Zhen ZhangXiao-Hua Yu

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