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: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 scRNAseq method to examine smooth muscle cell gene expression profile using Apoe and SMC specific TGFbR2 KO in Apoe background mice.
Project description:Abdominal aortic aneurysms (AAA), are defined by an increased aortic diameter and characterized by impairment of the extracellular matrix, macrophages infiltration and decreased density of smooth muscle cells. Our aim is to identify the key molecules involved in the pathogenesis of AAAs. This study investigated transcriptomic and proteomic profiles of macrophages from AAA patients (> 50 mm aortic diameter) and peripheral arterial occlusion (PAO) patients without AAA detected, who both needed a surgery.
Project description:Ascending aortic aneurysms (AscAA) are a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Lineage tracing analysis showed that loss of Notch1 in the SHF reduces the number of SHF-derived smooth muscle cells in the aortic root, and RNA-seq analysis demonstrated distinct in vivo expression patterns between lineage-specific regions of the ascending aorta. Finally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 independently predisposes to AscAA. These findings are the first to demonstrate a SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.
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:IL-1 plays an important role in atherosclerosis, and alters expression of a number of genes involved in atherosclerotic plaque development and progression. Smooth muscle cells play important roles in atherosclerotic plaque formation and stability, so this study was undertaken to determine the global effects of IL-1b on gene expression in smooth muscle cells in vitro. Cultured rat aortic smooth muscle cells were treated with IL-1b (2.5 ng/mL) or vehicle (0.1% BSA) for 24 hours prior to harvest.
Project description:Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor of atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigated its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduced lipid accumulation and suppressed activation of inflammatory and fibrotic pathways as well as lowered oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hindered the shift from a contractile to a synthetic phenotype. Together, we provide the first evidence that antagonizing STK25 signaling in human aortic endothelial and smooth muscle cells is atheroprotective, highlighting this kinase as a new potential therapeutic target for atherosclerotic disease.