Dataset Information

Novel Epigenetic Mechanisms of Endogenous CSE/H₂S in Smooth Muscle Cells for Abdominal Aortic Aneurysm [ChIP-Seq]

ABSTRACT: In this study, ChIP - seq was employed to investigate the impact of CSE on epigenetic modifications in vascular smooth muscle cells (VSMCs) and to uncover its influence on genome - wide DNA binding. We conducted ChIP - seq experiments on H3K9me3, H3K9ac, and H3K4me3 using primary smooth muscle cells from CSE knockout mice and wild - type (WT) mice after 24 - hour stimulation with Ang II. Our finding demonstrated that endogenous CSE/H₂S in smooth muscle regulates the expression of extracellular matrix through epigenetic modifications and participates in the occurrence and development of abdominal aortic aneurysm (AAA).

ORGANISM(S): Mus musculus

PROVIDER: GSE296864 | GEO | 2026/02/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Abdominal Aortic Aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. Activating transcription factor (ATF) 3 has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. Methods: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell (VSMC)-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 (rAAV9) vectors carrying ATF3, or shRNA-ATF3 with SM22α promoter were used in AngII (angiotensin II) induced AAA mice. In human and murine VSMCs, gain or loss of function experiments were performed to investigate the role of ATF3 in VSMC proliferation and apoptosis. Results: In both AngII-induced AAA mice and AAA patients, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in VSMC promoted AAA formation in AngII-induced AAA mice. PDGFRB was identified as the target of ATF3, which mediated VSMC proliferation in response to TNF-alpha at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our ChIP results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (Andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. Conclusions: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Dataset Information

Novel Epigenetic Mechanisms of Endogenous CSE/H₂S in Smooth Muscle Cells for Abdominal Aortic Aneurysm [ChIP-Seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets