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Project description:Background: Vascular calcification (VC) is a severe complication of chronic kidney disease (CKD) and increases cardiovascular morbidity and mortality. Extracellular vesicles (EVs) from bone mesenchymal stem cells (BMSCs) may influence vascular health through intercellular communication. This study investigated how CKD alters the anti-calcific function of BMSC-derived EVs, focusing on microRNA content, particularly miR-29a-3p. Methods: EVs were isolated from healthy and CKD-affected BMSCs and assessed for size, uptake by vascular smooth muscle cells (VSMCs), and miRNA content. High-phosphate-treated VSMCs and CKD rat models of vascular calcification were used to evaluate the effects of EVs on VC. Circulating miR-29a-3p was measured in hemodialysis patients and correlated with VC severity. Results: EVs from both groups showed comparable size and VSMC uptake. However, CKD-derived EVs had an altered miRNA profile, including markedly reduced miR-29a-3p, and showed diminished ability to inhibit phosphate-induced calcification. Restoration of miR-29a-3p suppressed calcification in vitro and in vivo. In hemodialysis patients, circulating miR-29a-3p was inversely associated with calcification severity. Conclusions: CKD impairs the anti-calcific function of BMSC-derived EVs partly through downregulation of EV-associated miR-29a-3p. Restoring miR-29a-3p may help mitigate VC in CKD, and circulating miR-29a-3p may serve as a clinical biomarker.
2026-07-01 | GSE301484 | GEO
Project description:VSMC gene in normal kdney and chronic kidney mice
| PRJNA955278 | ENA
Project description:Chronic kidney disease (CKD) accelerates vascular calcification (VC) via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways. We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. The miRNA transcriptome of sEVs revealed a depletion of several miRNAs in CKD. Their expression levels in sEVs from CKD patients were correlated to kidney function. This study revealed the transcriptomic landscape of miRNAs propagated in sEVs in CKD. We investigated the therapeutic potential of miRNAs in VC.
2022-12-31 | GSE217558 | GEO
Project description:We applied the transcriptome profiling (RNA-seq) for high-throughput profiling of genes changes in VSMC dedifferentiation. Rat primary VSMCs were divided into 3 groups, control, PDGF-BB, PDGF-BB+PJ34,and mRNA sequence were performed. We found that PDGF-BB could upregualted the genes involved in cell proliferation and migration, and downregulated the VSMC contractile genes, all of which could be reversed by PARP inhibitor PJ34. Then we knockdowned the co-factor Myocardin in VSMCs, and found the above effects of PJ34 were nearly abolished.Our study first provided the transcription changes by RNA-seq in VSMC dedifferentiation, and demonstrated the key roles of PARP1 and the PARylation process in VSMC phenotypic switch.
2018-09-20 | GSE103995 | GEO
Project description:Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction of the vascular smooth muscle cells (VSMCs) from circle of Willis (CoW) vessels mediates CA formation as they are the major cell type of the arterial wall and play a role in maintaining vessel integrity. Dimethyl fumarate (DMF), a first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation and reduce CA formation in a mouse model. Potential unwanted side effects of DMF on VSMC function have not been investigated yet. The present study characterizes the impact of DMF on VSMC using scRNA-seq in CoW vessels following CA induction and further explores its role in mitochondrial function using in vitro VSMC cultures. Two weeks of DMF treatment following CA induction impaired the transcription of the glutathione redox system and downregulated mitochondrial respiration genes in VSMCs. In vitro, DMF treatment increased lactate formation and enhanced the mitochondrial production of reactive oxygen species (ROS). These effects rendered VSMCs vul-nerable to oxidative stress and led to mitochondrial dysfunction and enhancement of apoptosis. Taken together, our data support the concept that the DMF-mediated antiproliferative effect on VSMCs is linked to disturbed antioxidative functions resulting in altered mitochondrial metabo-lism. This negative impact of DMF treatment on VSMCs may be linked to preexisting alterations of cerebrovascular function due to renal hypertension. Therefore, before severe adverse effects emerge, it would be clinically relevant to develop indices or biomarkers linked to this disturbed antioxidative function to monitor patients undergoing DMF treatment.
2024-06-20 | GSE268079 | GEO
Project description:Atherosclerosis is one of the causative factors leading to the development of cardiovascular disease. Angiotensin II (AngII) is implicated in the pathological processes underlying atherosclerosis. We investigated the AngII regulated gene expression in primary vascular smooth muscle cells (VSMC). VSMCs were isolated from the thoracic aorta of male Wistar rats. Serum deprived VSMCs were stimulated with 100 nM AngII or vehicle for 2 hours, then RNA-Sequencing was carried out.
2022-07-03 | E-MTAB-11863 | biostudies-arrayexpress
Project description:Conduit arterial disease in CKD is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to human stage 4-5 CKD. PTH and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased and VSMC transdifferentiation was absent. The CKD mice were not hypertensive, and cardiac hypertrophy was absent. Freshly excised cardiac tissue respirometry (Oroboros) showed ADP-stimulated O2 flux was diminished from 52 to 22 pmol/mg (p=0.022). RNAseq of cardiac tissue from CKD mice revealed significantly decreased levels of cardiac mitochondrial oxidative phosphorylation genes. The data reported here show that cardiac mitochondrial respiration is impaired in CKD in the absence of conduit arterial disease. This is the first report of the direct effect of CKD on cardiac respiration.
2024-02-23 | GSE255815 | GEO
Project description:Vascular smooth muscle cells (VSMCs) are a major cell type of the arterial wall and their functionality is associated with blood pressure regulation. Although royal jelly (RJ) has reported effects on anti-hypertension, the mechanism of blood pressure regulation by major royal jelly protein 1 (MRJP1), the most abundant RJ protein, is still unknown. Therefore, mrjp1 gene was delivered into mouse VSMCs to investigate how MRJP1 influences the VSMC functionality by functional and proteomic analysis.The data here are the proteomic analysis of triplicated control and MRJP1 expressing VSMCs.
2018-10-27 | PXD004207 | Pride
Project description:Background: Despite transcriptional control mechanisms of VSMC osteogenic transition having been extensively studied, posttranscriptional regulation is still awaiting elucidation. In the present study, we explore the mechanism of THOC5-dependent VSMCs osteochondrogenic switching. Methods: Von Kossa staining and immunohistochemistry staining were used to detect calcification and expression of THOC5 respectively. Thoc5 shRNA and Thoc5 overexpression lentivirus were used to modulate the expression of Thoc5. RNA-Seq combined with RIP-Seq was used to explore the target mRNAs that directly bind to THOC5, and FISH was used to confirm its subcellular localization. Results: Immunohistochemical staining showed significantly increased THOC5 expression in the calcified artery of CKD patients. Besides, calcification-induced increase of THOC5 expression was found in both in vivo and in vitro calcification models. The overexpression of Thoc5 relieves the calcification and osteogenic differentiation of VSMCs significantly in vitro, which is mainly manifested by the reduction of calcium ion deposition and the decreased expression of osteogenic markers. Furthermore, RNA-Seq revealed that THOC5 overexpression in osteogenic-induced VSMCs closely resembled the gene expression changes induced on TGF-β treatments in cultured VSMCs. In addition, overexpression of THOC5 alleviates the exacerbation of calcification in vivo. Our previous studies found that THOC5 displayed limited binding to VSMCs genomic DNA, so RIP-Seq was selected to detect target genes of THOC5. It was found that THOC5 directly interacts with Guanylate exchange factors (GEFs) mRNAs, and is required for their export. Thereby THOC5 maintaining RhoA GTPase activation contributes to increasing the expression of VSMCs contraction marker, which maintains the contraction phenotype of VSMCs. ROCK (Rho-kinase) inhibitor Y-27632 reversed the protective role of THOC5 on osteoblastic transdifferentiation and calcification, as well as the maintenance of the spindle morphology of VSMCs. Conclusions: Our data introduce the binding of THOC5 to GEFs as a novel mechanism contributing to maintaining VSMCs homeostasis and imply THOC5 as a potential intervention node for vascular calcification diseases.
2025-11-04 | GSE281368 | GEO
Project description:Background: Despite transcriptional control mechanisms of VSMC osteogenic transition having been extensively studied, posttranscriptional regulation is still awaiting elucidation. In the present study, we explore the mechanism of THOC5-dependent VSMCs osteochondrogenic switching. Methods: Von Kossa staining and immunohistochemistry staining were used to detect calcification and expression of THOC5 respectively. Thoc5 shRNA and Thoc5 overexpression lentivirus were used to modulate the expression of Thoc5. RNA-Seq combined with RIP-Seq was used to explore the target mRNAs that directly bind to THOC5, and FISH was used to confirm its subcellular localization. Results: Immunohistochemical staining showed significantly increased THOC5 expression in the calcified artery of CKD patients. Besides, calcification-induced increase of THOC5 expression was found in both in vivo and in vitro calcification models. The overexpression of Thoc5 relieves the calcification and osteogenic differentiation of VSMCs significantly in vitro, which is mainly manifested by the reduction of calcium ion deposition and the decreased expression of osteogenic markers. Furthermore, RNA-Seq revealed that THOC5 overexpression in osteogenic-induced VSMCs closely resembled the gene expression changes induced on TGF-β treatments in cultured VSMCs. In addition, overexpression of THOC5 alleviates the exacerbation of calcification in vivo. Our previous studies found that THOC5 displayed limited binding to VSMCs genomic DNA, so RIP-Seq was selected to detect target genes of THOC5. It was found that THOC5 directly interacts with Guanylate exchange factors (GEFs) mRNAs, and is required for their export. Thereby THOC5 maintaining RhoA GTPase activation contributes to increasing the expression of VSMCs contraction marker, which maintains the contraction phenotype of VSMCs. ROCK (Rho-kinase) inhibitor Y-27632 reversed the protective role of THOC5 on osteoblastic transdifferentiation and calcification, as well as the maintenance of the spindle morphology of VSMCs. Conclusions: Our data introduce the binding of THOC5 to GEFs as a novel mechanism contributing to maintaining VSMCs homeostasis and imply THOC5 as a potential intervention node for vascular calcification diseases.
2025-11-04 | GSE281115 | GEO