Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA150707 | ENA |
REPOSITORIES: ENA
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Project description:This study evaluated transcriptional effects of nanomaterials that have been proposed for use as platforms for drug delivery. We tested SiO2 that had been surface modified to have a positive zetapotential of different geometries as well PAMAM dendrimers with different surface charges. We tested these materials on human aortic endothelial cells (HAECs) since we were interested in determining if there was a toxicogenomic response in endothelial cells that may come into contact with drug delivery nanoplatforms. The most pronounced transcriptional response resulted from the SiO2 treatement - the most prevelant responses were cell cycle, lipid metabolism and pro-inflammatory responses - with fewer responses from the PAMAM dendrimers. The lipid metabolism responses may relate to teh positive surface character as this response was not observed in the G3.5-COOH dendrimers. Indeed, the G3.5-COOH dendrimers were non-toxic and did not demonstrate any consistent transcriptional response. Primary human aortic endothial cells (HAECs) were grown in 6 well plates (in 2 ml of medium) until they were >80% confluent by visual inspection. Daily media changes allowed continued growth for HAECs that demonstrate contact inhibition. The cells were then incubated with nanomaterials: surface modified SiO2 with worm and sphere goemetries (the spheres were 200 nm in diameter and the worm's cylindrical diameter 200 nm and the length was ~ 1000 nm); and PAMAM dendrimers with different surface charges (G3.5-COOH are negative and G4-NH2 are positive). RNA was collected after 4 and 24 hrs (one SiO2 worm sample was at 1.5 hrs due to space available on the 4-pack microarrays). Triplicate biological samples (indicated by the 'a', 'b', and 'c' designations in the sample names) were evaluated for gene expression changes by microarray analysis.
2013-12-20 | E-GEOD-35142 | biostudies-arrayexpress
Project description:This study evaluated transcriptional effects of nanomaterials that have been proposed for use as platforms for drug delivery. We tested SiO2 that had been surface modified to have a positive zetapotential of different geometries as well PAMAM dendrimers with different surface charges. We tested these materials on human aortic endothelial cells (HAECs) since we were interested in determining if there was a toxicogenomic response in endothelial cells that may come into contact with drug delivery nanoplatforms. The most pronounced transcriptional response resulted from the SiO2 treatement - the most prevelant responses were cell cycle, lipid metabolism and pro-inflammatory responses - with fewer responses from the PAMAM dendrimers. The lipid metabolism responses may relate to teh positive surface character as this response was not observed in the G3.5-COOH dendrimers. Indeed, the G3.5-COOH dendrimers were non-toxic and did not demonstrate any consistent transcriptional response.
2013-12-20 | GSE35142 | GEO
Project description:Transcriptional impact of MTHFD2 in Human Aortic Endothelial Cells
| PRJNA391168 | ENA
Project description:Analysis of gene expression in primary cultured human aortic endothelial cells (HAECs) and primary cultured human aortic smooth muscle cells (SMCs) with or without H2O2 or Collagen tripeptide (CTP)
2021-06-29 | GSE175612 | GEO
Project description:Super-selective intra-ophthalmic artery chemotherapy (SSIOAC) is an organ-specific drug-delivery strategy to treat retinoblastoma, the most common primary ocular malignancy in children. Unfortunately, recent clinical reports associate adverse vascular toxicities with SSIOAC using melphalan, the most commonly used chemotherapeutic. To explore the reason for the unexpected vascular toxicities, we have developed in vitro studies with human retinal endothelial cells to test the effects of the chemotherapeutics and a non-human primate model to monitor the SSIOAC treatment in real-time and post-treatment. Melphalan and carboplatin (another chemotherapeutic used to treat retinoblastoma via SSIOAC) triggered migration, proliferation, and apoptosis when used to treat human retinal endothelial cells. Melphalan was associated with increased adhesion of leukocytes to human retinal endothelial cells, and tended to increase with increased cell expression of adhesion proteins (ICAM-1) and soluble chemotactic factors (IL-8). Histopathology post-SSIOAC indicated vessel wall sloughing, leukostasis, and vessel occlusion. We have established an in vitro human cell culture model and a non-human primate model to evaluate strategies designed to obviate vascular side effects, and optimize the efficacy of SSIAOC and the drug preparations used in SSIOAC. 4 non-treated (CNT) vs. 4 carboplatin-treated primary human retinal endothelial cells (RECs).
2011-12-13 | E-GEOD-34379 | biostudies-arrayexpress
Project description:Super-selective intra-ophthalmic artery chemotherapy (SSIOAC) is an organ-specific drug-delivery strategy to treat retinoblastoma, the most common primary ocular malignancy in children. Unfortunately, recent clinical reports associate adverse vascular toxicities with SSIOAC using melphalan, the most commonly used chemotherapeutic. To explore the reason for the unexpected vascular toxicities, we have developed in vitro studies with human retinal endothelial cells to test the effects of the chemotherapeutics and a non-human primate model to monitor the SSIOAC treatment in real-time and post-treatment. Melphalan and carboplatin (another chemotherapeutic used to treat retinoblastoma via SSIOAC) triggered migration, proliferation, and apoptosis when used to treat human retinal endothelial cells. Melphalan was associated with increased adhesion of leukocytes to human retinal endothelial cells, and tended to increase with increased cell expression of adhesion proteins (ICAM-1) and soluble chemotactic factors (IL-8). Histopathology post-SSIOAC indicated vessel wall sloughing, leukostasis, and vessel occlusion. We have established an in vitro human cell culture model and a non-human primate model to evaluate strategies designed to obviate vascular side effects, and optimize the efficacy of SSIAOC and the drug preparations used in SSIOAC. 4 non-treated (MNT) vs. 4 melphalan-treated primary human retinal endothelial cells (RECs).
2011-12-13 | E-GEOD-34381 | biostudies-arrayexpress
Project description:Brain vascular aging is increasingly recognized as a critical therapeutic target for age-related cognitive decline. Oxidative stress, bioenergetic dysfunction, and molecular damage play central roles in the progression of vascular aging, contributing to cerebrovascular dysfunction and impaired cognitive function. While naturally occurring polyphenols such as resveratrol (RSV) have demonstrated potential in mitigating aging-related pathologies, their poor bioavailability and limited brain targeting efficiency significantly constrain their therapeutic impact. As a result, high doses or advanced drug delivery strategies are necessary to achieve meaningful physiological effects. We introduce a novel nanocarrier system designed to enhance RSV delivery to the cerebral endothelium by leveraging the natural formation of an apolipoprotein E (ApoE)-enriched protein corona around fusogenic liposomes (FL) in vivo. These nanoparticles directly fuse with cytoplasmic cell membranes and thus evade endocytosis. We found that once in the circulation FL spontaneously acquire a protein corona, which is highly enriched in ApoE, a key ligand for brain endothelial low-density lipoprotein receptors (LDLR). Based on this observation, we engineered an ApoE-functionalized protein corona around FL (ApoE-FL) to systematically evaluate whether this mechanism could be exploited for targeted brain delivery. Following optimization and physicochemical characterization, the RSV-loaded liposomes were evaluated in vitro using human cerebral microvascular endothelial cells and in vivo C57BL/6 aged mice to assess their therapeutic potential. Both FL and engineered ApoE-FL liposomal delivery systems exhibited a strong affinity for endothelial cell membranes in vitro. The knockdown of the ApoE receptor, low-density lipoprotein receptor-related protein 1 (LRP1), significantly reduced liposomal docking. Microscopy analysis revealed that both ApoE-FL and non-functionalized FL directly fused with endothelial plasma membranes, thus bypassing intracellular organelles and minimizing lysosomal degradation. This suggests that the naturally formed ApoE corona in vivo may contribute to efficient cerebrovascular targeting, a property successfully replicated by the engineered ApoE corona strategy. In vivo biodistribution and kinetic studies demonstrated that especially ApoE-FL achieved enhanced brain-targeting efficiency, prolonged cerebrovascular retention, and extended targeting distance along the arteriovenous axis. This emphasizes that fusogenic liposomes effectively engage almost the entire microvascular network, including capillaries and post-capillary venules. Functionally, fusogenic liposome-delivered RSV improved blood-brain barrier (BBB) integrity, enhanced neurovascular coupling (NVC) responses, and promoted brain vascularization in aged mice. Single-cell RNA sequencing (scRNA-seq) revealed enhanced endothelial angiogenesis and barrier protective transcriptional profiles in cerebrovascular cells treated with ApoE-FL/RSV, suggesting a molecular basis for the observed vascular benefits. Liposomal RSV delivery achieved near-complete cerebrovascular and cognitive rejuvenation in aged mice applying a 2000-fold lower RSV dose than oral administration used as control sample. Thus, ApoE-FL liposomes exhibited exceptionally high delivery efficiency in deeper brain regions, further expanding their therapeutic potential. These findings underscore the importance of targeted drug delivery in optimizing therapeutic outcomes and establish ApoE-functionalized fusogenic liposomes as a promising strategy for mitigating brain vascular aging and cognitive decline.
2026-03-24 | GSE325456 | GEO
Project description:Intermittent and sustained hypoxia exposures activate distinct transcriptional responses in human aortic endothelial cells
| PRJNA1172698 | ENA
Project description:Regulation of coding and non-coding genes is studied from primary human aortic endothelial cells (HAECs), venous endothelial cells (HUVECs), aortic smooth muscle cells (HASMCs) and macrophages (CD14+) under pro-atherogenic stimuli (hypoxia, oxPAPC and hypoxia+oxPAPC) by integrating three different sequencing techniques: GRO-seq, miRNA-seq and RNA-seq.
2021-05-14 | GSE154427 | GEO
Project description:Regulation of coding and non-coding genes is studied from primary human aortic endothelial cells (HAECs), venous endothelial cells (HUVECs), aortic smooth muscle cells (HASMCs) and macrophages (CD14+) under pro-atherogenic stimuli (hypoxia, oxPAPC and hypoxia+oxPAPC) by integrating three different sequencing techinques: GRO-seq, miRNA-seq and RNA-seq
2020-06-17 | GSE136813 | GEO