H3.3B controls aortic dissection progression by regulating vascular smooth muscle cells phenotypic transition and vascular inflammation.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229127 | GEO | 2024/04/06
REPOSITORIES: GEO
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Project description:To investigate the function H3f3b in the regulation of VSMC phenotypic transition, we infect VSMCs with shNT or shH3f3b virus.
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Project description:Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain–containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell–specific (VSMC-specific) Prdm16-knockout (Prdm16SMKO) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in Prdm16SMKO mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling. Prdm16 deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC apoptosis induced by Prdm16 deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.
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Project description:The response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to TiO2 nanotube arrays is studied through gene expression analysis. Microarrays revealed that nanotubes enhanced EC proliferation and motility, decreased VSMC proliferation, and decreased expression of molecules involved in inflammation and coagulation in both cell types. Network generated from significantly affected genes suggests that cells may be sensing nanotopographical cues via pathways previously implicated in sensing shear stress. DNA microarrays were used to analyze the response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to nanotopographical TiO2 surfaces. The experiment incorporated a 1 color design and used Agilent arrays that contained roughly 44,00 60mer probes that provide complete coverage of the human genome. 19 arrays were hybridized and represent 4 biological replicates for each group ( with the exception of group VSMC-NT30, which has 3 biological replicates). Data was analyzed separately for each cell type ( EC or VSMC). Gene expression comparisons were made between control cells grown on flat titanium (Ti) and cells grown on either 30nm nanotubes (NT30) or 100nm nantubes ( NT-100).
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Project description:The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 subjects were recruited for screening of differentially expressed plasma microRNAs. We found that miR-1204 was significantly increased in both plasma and aorta of elder patients with AAD, and was positively correlated with age. Cell senescence induced the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induced vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. miR-1204 aggravated angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuated β-aminopropionitrile monofumarate-induced AAD formation. Mechanistically, miR-1204 directly targeted myosin light chain kinase (MYLK) to promote VSMCs to acquire senescence-associated secretory phenotype (SASP) and lose their contractile phenotype. Overexpression of MYLK reversed miR-1204-induced VSMC senescence, SASP and contractile phenotype changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest aging aggravates AAD via 75 miR-1204-MYLK signaling axis.
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