Project description:Early transcriptomic response to n-LDL and ox-LDL in human vascular smooth muscle cells (hVSMC). We used microarrays with the aim of assessing early molecular changes that induce a response in the VSMC using native and oxidized low-density lipoprotein (n-LDL and ox-LDL).
Project description:Early transcriptomic response to n-LDL and ox-LDL in human vascular smooth muscle cells (hVSMC). We used microarrays with the aim of assessing early molecular changes that induce a response in the VSMC using native and oxidized low-density lipoprotein (n-LDL and ox-LDL). For each LDL internalization experiment, three biological replicates were used and the samples pooled with the aim of obtain three technical replicates (three arrays for condition).
Project description:Atherosclerosis (AT) is a chronic inflammatory disease characterized by the accumulation of inflammatory cells, lipoproteins and fibrous tissue in the walls of arteries. AT is the primary cause of heart attacks and stroke and the leading cause of death in westernized countries. To date, the pathogenesis of AT is not well-defined. Studies have shown that the dedifferentiation of contractile and quiescent vascular smooth muscle cells (SMC) to the proliferative, migratory and synthetic phenotype in the intima is pivotal for the onset and progression of AT. To further delineate the mechanisms underlying the pathogenesis of AT, we have analyzed the early molecular pathways and networks of SMC phenotype transformation as induced by the presence of minimally-oxidized LDL (moxLDL). 3 pooled samples were analyzed, one untreated control, one 3h after treatment, one 21h after treatment, no replicates
Project description:Atherosclerosis (AT) is a chronic inflammatory disease characterized by the accumulation of inflammatory cells, lipoproteins and fibrous tissue in the walls of arteries. AT is the primary cause of heart attacks and stroke and the leading cause of death in westernized countries. To date, the pathogenesis of AT is not well-defined. Studies have shown that the dedifferentiation of contractile and quiescent vascular smooth muscle cells (SMC) to the proliferative, migratory and synthetic phenotype in the intima is pivotal for the onset and progression of AT. To further delineate the mechanisms underlying the pathogenesis of AT, we have analyzed the early molecular pathways and networks of SMC phenotype transformation as induced by the presence of minimally-oxidized LDL (moxLDL).
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.
Project description:Analysis of hypoxia-exposed human pulmonary artery smooth muscle cells to identify the commonly regulated microRNAs by hypoxia. Results provide insight into the regulatory mechanism of hypoxic responses in vascular smooth muscle cells.
Project description:Analysis of hypoxia-exposed human pulmonary artery smooth muscle cells to identify the commonly regulated genes by hypoxia. Results provide insight into the regulatory mechanism of hypoxic responses in vascular smooth muscle cells.
2019-09-25 | GSE118362 | GEO
Project description:RNA Seq of ox-LDL treated vascular smooth muscle cells
Project description:Myeloperoxidase-oxidized LDLs (Mox-LDLs) trigger endothelial cells and participate in atherosclerosis. However, the mechanisms behind Mox-LDLs stimulation are not fully understood. Therefore, we used an untargeted proteomics approach to analyze human umbilical vein endothelial cells (HUVECs) after stimulation by Mox-LDLs. HUVECs (n=6) were exposed for 24 h to Mox-LDLs (0 or 100 µg/ml) with or without native LDLs (0 or 1 mg/m). Supernatant and cell lysate were then analyzed using LC-MS/MS. Mox-LDLs treatment of HUVECs led to changes in the expression of proteins implicated in hemostasis, cell adhesion, angiogenesis, inflammation and stress responses. We also observed cell reprogramming through increased mitochondrial activity. Mox-LDLs seem to induce mitochondrial activation and oxidative stress in the cell, likely reactive oxygen species mediated. We suggest that HUVECs then activate cytoprotective antioxidant coping mechanisms (glutathione synthesis, heme oxygenase-1) to survive. Mox-LDLs may also modulate hemostasis and inflammatory responses, both pro- and anti-inflammatory.
