Project description:Transcription factor FoxM1 is expressed in proliferating cells, and its expression is critical for cell proliferation in embryos and tumors. FoxM1 regulates a multi-gene transcriptional network for cell cycle regulation. We used microarrays to detail the global program of gene expression either directly or indirectly regulated by FoxM1, and distinct classes of up- and down-regulated genes. Experiment Overall Design: Human aortic vascular smooth muscle cells (HAVSMC) were transfected with FoxM1 siRNA and control siRNA for 48 hours. Total RNA was extracted, purified, and prepared for hybridization on Affymetrix microarrays.
Project description:Gene expression profiles of Rat aortic smooth muscle clonal isolates of PTEN knock-down and control wild-type. We used Affymetrix microarrays to detail the global program of gene expression changes between PTEN deficient and wild type smooth muscle cells. We identified distinct classes of up- and down-regulated genes during this process.
Project description:Vascular smooth muscle cells (VSMCs) phenotype switch has been thought to be critical to the development of thoracic aneurysm/dissection. To investigate the function SIRT6 in the regulation of VSMCs phenotype switch, we established mouse vascular smooth muscle cells in which each target gene has been knocked down by siRNA.
Project description:Vascular smooth muscle cells (VSMCs) phenotype switch has been thought to be critical to the development of thoracic aneurysm/dissection. To investigate the function EZH2 in the regulation of VSMCs phenotype switch, we established mouse vascular smooth muscle cells in which each target gene has been knocked down by siRNA.
Project description:Objective – Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no FDA-approved anti-calcific therapies. We hypothesized and validated that an unbiased screening approach would identify novel mediators of human vascular calcification. Approach and Results – We performed an unbiased quantitative proteomics and pathway network analysis that identified increased carnitine O-octanoyltransferase (CROT) in calcifying primary human coronary artery smooth muscle cells (SMCs). Additionally, human carotid artery atherosclerotic plaques contained increased immunoreactive CROT near calcified regions. CROT siRNA reduced fibrocalcific response in calcifying SMCs. In agreement, histidine 327 to alanine point mutation inactivated human CROT fatty acid metabolism enzymatic activity and suppressed SMC calcification. CROT siRNA restored mitochondrial proteome alterations and suppressed mitochondrial fragmentation in calcifying SMCs. Lipidomics analysis of SMCs incubated with CROT siRNA revealed increased eicosapentaenoic acid, a vascular calcification inhibitor. CRISPR/Cas9-mediated Crot deficiency in low-density lipoprotein receptor-deficient mice reduced aortic and carotid artery calcification without altering bone density, or liver and plasma cholesterol and triglyceride concentrations. Conclusions – CROT is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an anti-fibrocalcific therapy.
Project description:We used NGS-derived transcriptome profiling (RNA-seq) to compare the transcriptional difference between human aortic smooth muscle cells (HASMCs) transfected with 30nM siRNA targeting BAF60a (siBAF60a) or non-targeting siRNA (siControl)
Project description:Transcriptomics analysis of human coronary artery smooth muscle cells cultured in calcium-phosphate medium (CaP) to induce a mineralized extracellular matrix. To study the underlying molecular mechanisms driving vascular calcification, we analyzed the transcriptome of calcium-phosphate calcified human cronary aortic smooth muscle cells on day 3.
Project description:Platelet-derived growth factor (PDGF) signalling and the subsequent activation of the calcium ion channel, ORAI1 are critical drivers of pathological remodelling of native vascular smooth muscle cells to proliferative state, which is a process associated with various vascular diseases. This study aims to reveal transcriptional networks altered following ORAI1 inhibition in vascular smooth muscle cells. To study the effect of ORAI1 inhibition on VSMC biology, we performed RNA-Seq analysis of PDGF-stimulated primary human aortic smooth muscle cells treated with either ORAI1 inhibitor, (n=4) or with vehicle (n=4), and investigated the effect of ORAI1 inhibition on the transcriptional response of cells.
Project description:Effects of TRPC1 silencing on whole-transcriptome gene expression were determined in human primary aortic vascular smooth muscle cells using whole-transcriptome gene expression profiling.
