Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27600600_1.fastq.gz | Fastqsanger.gz | |||
| SRR27600600_2.fastq.gz | Fastqsanger.gz | |||
| SRR27600601_1.fastq.gz | Fastqsanger.gz | |||
| SRR27600601_2.fastq.gz | Fastqsanger.gz | |||
| SRR27600602_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 116 |
Similar Datasets
Project description:In this study, we aim to investigate the role of vascular smooth muscle cell (VSMC) NFATc3 in the development of AAD and establish NFATc3 as a novel target to treat AAD. We used VSMC-specific NFATc3 knockout mice in AAD model of BAPN treatment. The molecular mechanisms underlying NFATc3 function were investigated using RNA-seq analysis on aortas with BAPN treatment.
2025-07-30 | GSE234349 | GEO
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.
2024-04-02 | GSE253747 | GEO
Project description:Aortic aneurysm and dissection (AAD) is a life-threatening disease without effective pharmacological treatments. The progressive loss of vascular smooth muscle cells (VSMCs) is the fundamental pathophysiological basis for AAD, but the underlying mechanisms are largely unknown. Sirtuin 6 (SIRT6), a class III histone deacetylase, is critical for maintenance of VSMC homeostasis and consequent prevention of vascular remodeling-related diseases. However, its role in AAD development requires further investigation. Here, we show that SIRT6 expression was significantly reduced in VSMCs of the thoracic aorta in AAD patients. Sirt6 deficiency in VSMCs dramatically accelerated angiotensin Ⅱ (Ang Ⅱ) infusion-induced AAD formation and rupture even without an Apoe-deficient background. In vitro studies demonstrated that Sirt6 deficiency led to mitochondrial dysfunction and accelerated VSMC senescence. Mechanistically, SIRT6 could bind and deacetylate NRF2, a key transcription factor for mitochondrial biogenesis, however, Sirt6 deficiency inhibited NRF2 and reduced mRNAs encoding mitochondrial complex. Notably, MDL-811, a newly developed small-molecule SIRT6 agonist, effectively reversed Ang Ⅱ-induced mitochondrial dysfunctions in human aortic smooth muscle cells. More importantly, MDL-811 also mitigated AAD progression in mice. These findings suggest that SIRT6 plays a protective role in AAD development and targeting SIRT6 with small-molecule activators such as MDL-811 could represent a promising therapeutic strategy for AAD.
2025-03-07 | GSE290902 | GEO
Project description:The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. 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.
2024-04-02 | GSE255157 | GEO
Project description:Acute aortic dissection (AAD) is one of the major aortic diseases that occurs without a preceding symptom and often results in sudden death. Despite the recent advances in cardiovascular medicine, AAD remains a serious problem because its molecular pathogenesis is largely unknown. In this paper, we report our serendipitous discovery that stress-induced expression of tenascin C (TNC), a member of matricellular proteins, is the protection mechanism of aorta to prevent AAD. The aortic wall stress imposed by the aortic stiffening and the angiotensin II infusion caused the strong induction of TNC in wild type mouse aorta without gross morphological changes. While TNC knockout mice at the baseline showed no morphological, histological or biomechanical abnormalities of aorta, deletion of TNC gene rendered the aorta susceptible to AAD upon the aortic stress. The stressed TNC-null aorta showed the loss of the tensile strength due to the insufficient expression of extracellular matrix proteins and the exaggerated proinflammatory response before the onset of AAD. Therefore, TNC works as a stress-activated molecular damper both by reinforcing the tensile strength and by limiting the excessive proinflammatory response in aorta. Thus far, the molecular event that leads to the AAD development has been unclear because of the unpredictable nature of the AAD onset. This study sheds light on the previously unrecognized tissue protection mechanism that converts the potentially harmful stress response into the active reinforcement of the aorta, of which failure leads to the development of AAD. Although TNC is expressed in various tissues upon the mechanical and proinflammatory stimuli, its role has long been a mystery. Our data uncovered the adaptive role of TNC in aorta that must be resilient to the continuous hemodynamic and humoral stress for lifetime.
2015-03-27 | GSE36899 | GEO
Project description:Background: Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal condition. Identifying mechanisms that drive aortic degeneration is a crucial step in developing an effective pharmacologic treatment to prevent disease progression. Recent evidence has indicated that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical role in vascular inflammation and destruction. Here, we examined the involvement of this mechanism in aortic degeneration and sporadic AAD formation. Methods: The presence of cytosolic DNA in aortic cells and activation of the STING pathway were examined in aortic tissues from patients with sporadic ascending thoracic AAD. The role of STING in AAD development was evaluated in Sting-deficient (Stinggt/gt) mice in a sporadic AAD model induced by challenging mice with a combination of a high-fat diet and angiotensin II. We also examined the direct effects of STING on SMC death and macrophage activation in vitro. Results: In human sporadic AAD tissues, we observed the presence of cytosolic DNA in SMCs and macrophages and significant activation of the STING pathway. In the sporadic AAD model, Stinggt/gt mice showed significant reductions in challenge-induced aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions. Single-cell transcriptome analysis revealed that aortic challenge in wild-type mice induced the DNA damage response, the inflammatory response, dedifferentiation and cell death in SMCs, and matrix metalloproteinase expression in macrophages. These changes were attenuated in challenged Stinggt/gt mice. Mechanistically, nuclear and mitochondrial DNA damage in SMCs and the subsequent leak of DNA to the cytosol activated STING signaling, which induced cell death through apoptosis and necroptosis. In addition, DNA from damaged SMCs was engulfed by macrophages in which it activated STING and its target interferon regulatory factor 3, which directly induced matrix metalloproteinase-9 expression. We also found that pharmacologically inhibiting STING activation partially prevented AAD development. Conclusions: Our findings indicate that the presence of cytosolic DNA and subsequent activation of cytosolic DNA sensing adaptor STING signaling represent a key mechanism in aortic degeneration and that targeting STING may prevent sporadic AAD development.
2025-09-30 | GSE214595 | GEO
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 miR-1204-MYLK signaling axis.
2024-04-01 | PXD048658 | Pride
Project description:The estimation of the post-mortem interval (PMI) and the age-at-death (AAD) are crucial steps in the medico-legal investigation of unidentified human remains. Current methods to estimate PMI and AAD suffer from a lack of accuracy and objectivity, particularly when the remains are in an advanced state of decomposition. Recently, proteomics studies using animal models have identified potential biomarkers for PMI and AAD estimation. This study investigated the human bone proteome in four human body donors studied throughout decomposition outdoors. We compared different bone tissues (tibia and iliac crest) from body donors of known AAD, and compared bone samples taken shortly after death to bone samples upon complete skeletonization of the body. The effects of ageing phenomena (in vivo and post-mortem) and the surrounding environment on the variability and abundancy of the bone proteome were assessed.
2021-09-09 | PXD019693 | Pride