生物
血管平滑肌
炎症
主动脉夹层
基因敲除
表型
癌症研究
细胞生物学
组蛋白
免疫学
基因
内科学
内分泌学
主动脉
遗传学
医学
平滑肌
作者
Xuelin Zhang,Yang Che,Lin Mao,Dandan Li,Jianqing Deng,Yilong Guo,Quanyi Zhao,Xingzhong Zhang,Li Wang,Xiang Gao,Yinan Chen,Tao Zhang
出处
期刊:Genomics
[Elsevier]
日期:2023-07-16
卷期号:115 (5): 110685-110685
被引量:4
标识
DOI:10.1016/j.ygeno.2023.110685
摘要
Aortic dissection is a devastating cardiovascular disease with a high lethality. Histone variants maintain the genomic integrity and play important roles in development and diseases. However, the role of histone variants in aortic dissection has not been well identified. In the present study, H3f3b knockdown reduced the synthetic genes expression of VSMCs, while overexpressing H3f3b exacerbated the cellular immune response of VSMCs induced by inflammatory cytokines. Combined RNA-seq and ChIP-seq analyses revealed that histone variant H3.3B directly bound to the genes related to extracellular matrix, VSMC synthetic phenotype, cytokine responses and TGFβ signaling pathway, and regulated their expressions. In addition, VSMC-specific H3f3b knockin aggravated aortic dissection development in mice, while H3f3b knockout significantly reduced the incidence of aortic dissection. In term of mechanisms, H3.3B regulated Spp1 and Ccl2 genes, inducing the apoptosis of VSMCs and recruiting macrophages. This study demonstrated the vital roles of H3.3B in phenotypic transition of VSMCs, loss of media VSMCs, and vascular inflammation in aortic dissection.
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