Project description:To determine how gene expression is altered in aorta tissue in response to aortic aneurysm disease. Thoracic or abdominal aorta tissue was isolated from patients requiring surgery due to aortic aneurysm or other (control) reason.
Project description:We report dynamic temporal and spatial smooth muscle cell phenotype modulation using aortic single cell RNA sequencing in a murine model of Marfan syndrome (Fbn1C1041G/+) and littermate controls. Aortic root/ascending aortic tissue samples from both genotypes were studied at 4 and 24 weeks of age. The non-aneurysmal descending thoracic aorta was also studied at 24 weeks. Finally human aortic tissue from a Marfan syndrome patient undergoing aneurysm repair surgery was studied.
Project description:In this study, we identified various cell clusters in human normal/sporadic TAA ascending aorta samples by single-cell RNA sequencing (scRNA-seq), and discovered the senescent vascular smooth muscle cells (VSMCs) significantly increased in TAA samples. Then we explored the molecular basis of TAA progression, and recognized the key regulators and pathways involved in the TAA progression regulation.
Project description:To discover novel biomarkers for aortic aneurysm, serum samples of patients with thoracic aortic aneurysm were fractionated, tryptic digested, and subjected to proteome analysis.
Project description:Aortic smooth muscle cell (SMC) phenotype modulation is a central feature of cell-mediated pathology in Marfan syndrome aortic aneurysm and Klf4 is proposed to contribute to this process. We generated mice with smooth muscle cell-specific Klf4 deletion using an Myh11-creERT2 transgene, induced deletion at 8 weeks and performed single cell RNA sequencing at 24 weeks on whole aortic root tissues.
Project description:Aneurysmatic and dissection cells show a specific alteration of gene expression, which allow a disease specific distinction. We used microarrays to analyse the cellular gene expression of controls, thoracic aortic aneurysm, and aortic dissection.
Project description:In the present study, we evaluated miRNA expression profiles of 32 patient aortic aneurysm tissue and plasma samples using Illumina next-generation sequencing platform. A total of 20 miRNA were differentially expressed in tissues, 17 miRNAs - in plasma samples. Differentially expressed miRNAs determined in the present study could be applied for thoracic ascending aneurysm diagnosis.
Project description:Smooth muscle cell TGFβ signaling is one of the primary drivers of smooth muscle cell maturation. Inhibition of smooth muscle cell TGFβ signaling in hyperlipidemic mice induces vessel wall inflammation and vessel wall dilation/dissection and leads aortic aneurysm. We performed bulk RNAseq method to examine smooth muscle cell gene expression profile using fresh human tissues from normal aortic media smooth muscle cells and aneurysm aortic media smooth muscle cells.
Project description:Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. In this study, protein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. To verify it, we constructed aorta-on-a-chip to replicate the rhythmic tensile on human aorta, on which human aortic smooth muscle cells (HAoSMCs) endured a microenvironment of biomimetic strain unattainable in animal models. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) rescued the mitochondrial dysfunction in HAoSMCs from BAV-TAA patients. These findings suggest that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA.