Comparison of intimal and medial calcification in vitro
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA872009 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-18 | GSE211752 | GEO
Project description:Vascular calcification is the ectopic deposition of calcium hydroxyapatite minerals in arterial wall. However, the underlying molecular mechanisms regulating vascular calcification remain incompletely understood. In this study, we applied RNA sequencing to explore the mechanism of vascular calcificaiton in both medial and atherosclerotic vascular calcification models.
2021-02-23 | GSE159832 | GEO
Project description:We reported the cellular heterogeneity in the whole aorta (adventitial and medial/intimal layers).
2020-03-31 | GSE140811 | GEO
Project description:Cardiovascular diseases often manifest with vascular calcification. Vascular calcification is an active process orchestrated by contractile vascular smooth muscle cell (VSMC) phenotypic switch to an osteoblast-like cell. Here, we identified that the DNA demethylase, Tet2 (Ten-eleven translation 2), safeguards VSMCs from transitioning into the osteogenic lineage and loss of Tet2 promotes development and progression of vascular calcification. Tet2 was among the most significantly downregulated epigenetic markers in calcified aortas. VSMC-specific loss of Tet2 promoted VSMC osteogenic differentiation and enhanced vascular calcification as evidenced histologically, molecularly, and hemodynamically. In vivo studies further indicated that Tet2 inhibits calcification-associated VSMC apoptosis and medial thinning. Notably, calcified regions were enriched in a Trem2hi (triggered receptor expressed on myeloid cells 2) macrophage subpopulation. Intervention studies using high-dose ascorbate to enhance Tet2 enzymatic activity resulted in significantly reduced medial aortic calcification and improved aortic structural integrity in mice. Ascorbate treatment in human aorta organ cultures was sufficient to reduce calcification development in diseased tissues, and restore contractile properties to the calcified aorta. This study highlights the potential clinical impact of modulating Tet2 activity in managing cardiovascular disorders associated with vascular calcification.
2025-07-01 | GSE294266 | GEO
Project description:Diffuse intimal thickening (DIT) is a preclinical stage of atherogenesis in humans that does not exist in commonly used mouse models of atherosclerosis. Vascular smooth muscle cells (SMCs) are the predominant cell type that occupies the intimal and medial layers of human coronary arteries. The intimal layer of DIT is particularly prone to developing atherosclerosis later in life. Differences in the molecular features between the intimal and medial layers of DIT regions may represent the earliest changes that promote atherogenesis in humans, and can be studied by spatial molecular phenotyping.
2025-02-11 | GSE283269 | GEO
Project description:RNA-seq data of aortas with atherosclerotic or medial calcification
| PRJNA670795 | ENA
Project description:PurposeTo assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC).MethodsWe conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151).ResultsFemoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC compared to absence of calcification. Smoking and low ankle-brachial-index (ABI) were associated with higher prevalence of IAC and high ABI was associated with less IAC. Compared to patients with IAC, patients with MAC more often had diabetes, have a high ABI and were less often smokers. Inactive Matrix-Gla Protein was associated with increased MAC prevalence, while osteonectin was associated with decreased risk of MAC, compared to IAC.ConclusionsWhen femoral calcification is present, the majority of the patients have IAC or MAC throughout the lower extremity, which have different associated risk factor profiles.
| S-EPMC7357737 | biostudies-literature
Project description:IntroductionVascular calcification (VC) is a major risk factor for cardiovascular morbidity and mortality. Depending on the location of mineral deposition within the arterial wall, VC is classified as intimal and medial calcification. Using in vitro mineralization assays, we developed protocols triggering both types of calcification in vascular smooth muscle cells (SMCs) following diverging molecular pathways.Materials and methods and resultsHuman coronary artery SMCs were cultured in osteogenic medium (OM) or high calcium phosphate medium (CaP) to induce a mineralized extracellular matrix. OM induces osteoblast-like differentiation of SMCs-a key process in intimal calcification during atherosclerotic plaque remodeling. CaP mimics hyperphosphatemia, associated with chronic kidney disease-a risk factor for medial calcification. Transcriptomic analysis revealed distinct gene expression profiles of OM and CaP-calcifying SMCs. OM and CaP-treated SMCs shared 107 differentially regulated genes related to SMC contraction and metabolism. Real-time extracellular efflux analysis demonstrated decreased mitochondrial respiration and glycolysis in CaP-treated SMCs compared to increased mitochondrial respiration without altered glycolysis in OM-treated SMCs. Subsequent kinome and in silico drug repurposing analysis (Connectivity Map) suggested a distinct role of protein kinase C (PKC). In vitro validation experiments demonstrated that the PKC activators prostratin and ingenol reduced calcification triggered by OM and promoted calcification triggered by CaP.ConclusionOur direct comparison results of two in vitro calcification models strengthen previous observations of distinct intracellular mechanisms that trigger OM and CaP-induced SMC calcification in vitro. We found a differential role of PKC in OM and CaP-calcified SMCs providing new potential cellular and molecular targets for pharmacological intervention in VC. Our data suggest that the field should limit the generalization of results found in in vitro studies using different calcification protocols.
| S-EPMC9530266 | biostudies-literature
Project description:Interventions: cephalo-medial-to-lateral approach group:underwent laparoscopic cephlo-medial-to-lateral approach;conventional medial approach group:underwent conventional laparoscopic medial approach
Primary outcome(s): Three-year overall survival
Study Design: Randomized parallel controlled trial
| 2665288 | ecrin-mdr-crc
Project description:Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease (CKD), diabetes mellitus, and aging individuals. We previously showed that orphan nuclear receptor NR4A3 is a key regulator in the progression of apolipoprotein (apo) A-IV-induced atherosclerosis; however, little is known about its role in vascular calcification. NR4A3 expression was upregulated in calcified aortic tissues from CKD mice or 1,25(OH)2VitD3 overload-induced mice, and in human calcified aorta. NR4A3 deficiency preserved VSMCs contractile phenotype, inhibited the expression of osteoblast differentiation-related genes, and reduced calcium deposition in the vasculature.
2024-05-14 | GSE254075 | GEO