To examine vascular smooth muscle cells (VSMC) under four conditions
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31928 | GEO | 2011/09/06
SECONDARY ACCESSION(S): PRJNA145041
REPOSITORIES: GEO
Similar Datasets
Project description:Vascular calcification is a hallmark of atherosclerosis and end-stage renal disease (ESRD). However, the molecular mechanism of vascular calcification is poorly understood. Diabetes mellitus is increasingly recognized as the most important cause for atherosclerosis and ESRD. Emerging evidence supports the concept that vascular calcification resembles the process of osteogenesis, in which the vascular smooth muscle cells (VSMC) undergo osteochondrogenic differentiation. Recently, we have established an in vitro calcification system with primary mouse VSMC. With the use of osteogenic stimuli, we induced trans-differentiation of primary mouse VSMC into bone-like cells. Interestingly stroptozotocin (STZ), O-GlcNAcase inhibitor and a drug that has been used to induce diabetes in mice, was able to induce calcification of VSMC and the expression of the osteogenic transcription factor Runx2, suggesting glycosylation may be involved in regulation of Runx2. We have reported an essential role of Runx2 in oxidative stress-induce VSMC calcification and have recently generated a tissue specific mouse with Runx2 ablation in smooth muscle cells. Therefore, we will use STZ and other relevant reagents in the glucose synthesis/metabolism pathways as stimuli for VSMC calcification to characterize the glycogene profiles during VSMC calcification. Results from VSMC of Runx2 knockout mice will be compared with those from control mice to determine the regulation of calcification-associated glycogenes by Runx2 in response to STZ. These studies will provide foundation for further mechanistic studies and may lead to identification of novel strategies and targets for diabetes-induced vascular calcification. To examine vascular smooth muscle cells (VSMC) under two conditions: 1) wild-type VSMC differentiated into bone-like cells with osteogenic media, 2) wild-type VSMC treated with STZ and osteogenic media
2011-09-05 | E-GEOD-31928 | biostudies-arrayexpress
Project description:Vascular calcification is a common manifestation of atherosclerosis and involves cell-mediated processes similar to the formation of bone (osteogenesis). Elevated plasma levels of homocysteine are an independent risk factor for atherosclerotic vascular disease but the underlying mechanisms remain unclear. We postulated that hcy can modulate the cells involved in atherosclerosis to promote calcification. Cell experiments were performed to assess the effect of homocysteine on the osteogenic differentiation of aortic smooth muscle cells (AoSMC). Keywords: dose repsonse comparison To study the ability of homocysteine to induce osteogenic differentiation, AoSMC were cultured in T75 flasks (7.5x10E5 /mL) in growth medium with 0, 10 and 100 μmol/L DL-homocysteine. Four biological replicates were prepared for each condition. After 14 days, RNA was extracted from cells and the expression levels of osteogenic genes were compared between the different conditions of homocysteine concentration.
2008-10-21 | E-GEOD-9490 | biostudies-arrayexpress
Project description:Vascular calcification is a complex process and has been associated with aging, diabetes, chronic kidney disease (CKD). Although there have been several studies studying the role of miRNAs (miRs) in bone osteogenesis, little is known about the role of miRs in vascular calcification and their role in the pathogenesis of vascular abnormalities. Matrix vesicles (MV) are known to play an important role in initiating vascular smooth muscle cell (VSMC) calcification. In the present study, we performed miRNA microarray analysis to identify the dysregulated miRs between MV and VSMC derived from CKD rats to understand the role of post-transcriptional regulatory networks governed by these miRNAs in vascular calcification and to uncover the differential miRNA content of MV. The percentage of miRNA to total RNA was increased in MV compared to VSMC. Comparison of expression profiles of miRNA by microarray demonstrated 33 miRs to be differentially expressed with the majority (~ 57%) of them down-regulated. Target genes controlled by differentially expressed miRNAs were identified utilizing two different complementary computational approaches Miranda and Targetscan to understand the functions and pathways that may be affected due to the production of MV from calcifying VSMC thereby contributing to the regulation of genes by miRs. We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched. Signaling pathways identified included MAP-kinase and wnt signaling that have previously been shown to be important in vascular calcification. In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce. This suggests that miRs may play a very important regulatory role in vascular calcification in CKD by controlling an extensive network of post-transcriptional targets. Compare miRNA from matrix vesicles to miRNA from vascular smooth muscle cells that gave rise to the matrix vesicles from 3 sets of MV and VSMC derived from 3 normal and 3 CKD rats
2015-06-12 | E-GEOD-68913 | biostudies-arrayexpress
Project description:Vascular calcification is a common manifestation of atherosclerosis and involves cell-mediated processes similar to the formation of bone (osteogenesis). Elevated plasma levels of homocysteine are an independent risk factor for atherosclerotic vascular disease but the underlying mechanisms remain unclear. We postulated that hcy can modulate the cells involved in atherosclerosis to promote calcification. Cell experiments were performed to assess the effect of homocysteine on the osteogenic differentiation of aortic smooth muscle cells (AoSMC). Keywords: dose repsonse comparison
2008-10-21 | GSE9490 | GEO
Project description:Background: Ectopic vascular calcifications represent a major clinical problem associated with cardiovascular disease and mortality. However, the mechanisms underlying pathological vascular calcifications are largely unknown hampering the development of therapies to tackle this life threatening medical condition. Results: In order to gain insight into the genes and mechanisms driving this pathological calcification process we analyzed the transcriptional profile of calcifying vascular smooth muscle cells (C-VSMCs). These profiles were compared to differentiating osteoblasts, cells that constitute their physiological calcification counterparts in the body. Overall the transcriptional program of C-VSMC and osteoblasts did not overlap. Several genes, some of them relevant for bone formation, were distinctly modulated by C-VSMCs which did not necessarily lose their smooth muscle cell markers while calcifying. Bioinformatics gene clustering and correlation analysis disclosed limited bone-related mechanisms being shared by two cell types. Extracellular matrix (ECM) and biomineralization genes represented common denominators between pathological vascular and physiological bone calcifications. These genes constitute the strongest link between these cells and represent potential drivers for their shared end-point phenotype. Conclusions: the analyses support the hypothesis that VSMC trans-differentiate into C-VSMCs keeping their own identity while using mechanisms that osteoblasts use to mineralize. The data provide novel insights into groups of genes and biological processes shared in MSC and VSMC osteogenic differentiation. The distinct gene regulation between C-VSMC and osteoblasts might hold clues to find cell-specific pathway modulations, opening the possibility to tackle undesired vascular calcifications without disturbing physiologic bone formation and vice versa. Total RNA obtained from hMSC and hVSMC cultured in osteogenic differentiation medium supplemented with 1.8 mM Ca2+ for 0, 2, 8, 12 or 25 days respectively. For each timepoint 3 replicates were used, with exception for day 0 where 4 replicates were collected.
2014-10-10 | E-GEOD-37558 | biostudies-arrayexpress
Project description:Transcriptomics analysis of human coronary artery smooth muscle cells cultured in osteogenic medium (OM) to induce a mineralized extracellular matrix. To study the underlying molecular mechanisms driving vascular calcification, we analyzed the transcriptome of osteogenic medium (OM)-calcified human coronary artery smooth muscle cells on day 7.
2022-09-18 | GSE211722 | GEO
Project description:Vascular Calcification (VC) is a life threatening cardiovascular complication that accounts for high death rates particularly in association with diabetes, atherosclerosis and Chronic Kidney Disease (CKD. during VC, Vascular Smooth Muscle Cells (VSMCs) undergo reprogramming into osteoblast-like cells in response to calcium and phosphate mineral imbalance in CKD patients. This osteogenic switch is driven by the expression of several bone markers such as Runt- related transcription factor 2 (Runx2), Alkaline Phosphatase (ALP), Osteopontin (OPN), Matrix-Gla Protein (MGP), Osteocalcin (OCN), Type I Collagen (COL1), and Bone Sialo Proteins (BSPs). Recent studies showed that VSMCs secrete heterogeneous populations of Extracellular Vesicles (EVs)11 that are enriched under physiological conditions by calcification inhibitors such as Fetuin-A and MGP12,13,14. Interestingly, under pathological conditions, secreted EVs have a pro-calcifying profile and thereby act as nucleating foci for hydroxyapatite crystallization and propagation11,15. Electron Microscopy based studies revealed that EVs were embedded between collagen and elastin fibrils of arterial walls suggesting that calcification can be initiated through the EVs’ direct physical interaction with them13,16. We previously showed that a specific oligogalacturonic acid with a degree of polymerization of 8 (DP8) was able to inhibit vascular calcification. This inhibition was partly due to a decrease of osteogenic markers’s expression but also to the masking of a consensus sequence found in COL1 i.e. GFOGER sequence, thus preventing EVs from binding to COL1. Although the use of DP8 in-vivo seems to be compromised due to probable enzymatic digestion, these results suggested that the inhibition of VSMCs’ osteogenic switch and the prevention of EVs-COL1 interaction could represent new potential therapeutic targets for inhibiting VC17. Since we have already showed that the triple-helical GFOGER consensus sequence forms a preferential binding site for EVs17, we thereby chemically synthesized a GFOGER peptide in order to determine its ability to inhibit VC on VSMCs and on an aortic ring ex-vivo model. We also aim to decipher the mechanisms of inhibition by investigating the osteogenic markers’ expression as well as the protein content of secreted EVs in the presence of the GFOGER peptide.
2020-10-23 | PXD018169 | Pride
Project description:Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the prolonged accumulation of advanced glycation end products (AGEs) induced by hyperglycemia may be closely related to the pathogenesis of aortic calcification. However, the mechanisms underlying this association remain unclear. In the current study, we investigated the role of vascular smooth muscle cell nuclear factor 90/110 (NF90/110) in mediating AGEs accumulation and accelerating diabetic atherosclerotic calcification. Using vascular smooth muscle cells (VSMCs), human samples, and mouse models, we found that hyperglycemia-mediated AGEs markedly increased VSMC NF90/110 activation both in human and mouse atherosclerotic calcified tissues with diabetes. Silencing of NF90/110 in vitro and genetic deletion of VSMC NF90/110 in mice decreased obviously AGEs-induced arteriosclerotic calcification. Mechanistically, AGEs increased the activity of NF90, which then enhanced ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase, F-box, and WD repeat domain 7 (FBXW7), thus causing the accumulation of more AGEs. Furthermore, AGEs accumulation accelerated diabetic atherosclerotic calcification by inducing VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Collectively, our study demonstrated the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic arteriosclerotic calcification. These novel findings elucidate a pivotal mechanism underlying AGE-induced diabetic atherosclerotic calcification and provide a framework for potential interventions against diabetic vascular complications.
2024-04-02 | GSE253682 | GEO
Project description:Vascular calcification is a complex process and has been associated with aging, diabetes, chronic kidney disease (CKD). Although there have been several studies studying the role of miRNAs (miRs) in bone osteogenesis, little is known about the role of miRs in vascular calcification and their role in the pathogenesis of vascular abnormalities. Matrix vesicles (MV) are known to play an important role in initiating vascular smooth muscle cell (VSMC) calcification. In the present study, we performed miRNA microarray analysis to identify the dysregulated miRs between MV and VSMC derived from CKD rats to understand the role of post-transcriptional regulatory networks governed by these miRNAs in vascular calcification and to uncover the differential miRNA content of MV. The percentage of miRNA to total RNA was increased in MV compared to VSMC. Comparison of expression profiles of miRNA by microarray demonstrated 33 miRs to be differentially expressed with the majority (~ 57%) of them down-regulated. Target genes controlled by differentially expressed miRNAs were identified utilizing two different complementary computational approaches Miranda and Targetscan to understand the functions and pathways that may be affected due to the production of MV from calcifying VSMC thereby contributing to the regulation of genes by miRs. We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched. Signaling pathways identified included MAP-kinase and wnt signaling that have previously been shown to be important in vascular calcification. In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce. This suggests that miRs may play a very important regulatory role in vascular calcification in CKD by controlling an extensive network of post-transcriptional targets.
2015-06-12 | GSE68913 | GEO
Project description:Loss of contractility and acquisition of an epithelial phenotype of vascular smooth muscle cells (VSMCs) are key events in proliferative vascular pathologies such as atherosclerosis and post-angioplastic restenosis. There is no proper cell culture system allowing VSMC differentiation so that it is difficult to delineate the molecular mechanism responsible for proliferative vasculopathy. We investigated whether a micro-patterned substrate could restore the contractile phenotype of VSMCs in vitro. To induce and maintain the differentiated VSMC phenotype in vitro, we introduced a micro-patterned groove substrate to modulate the morphology and function of VSMCs.
2013-11-14 | E-MTAB-1888 | biostudies-arrayexpress