Aorta intimal macrophages prevent the formation of intravascular clots in regions of turbulent flow
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA679463 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13084596_1.fastq.gz | Fastqsanger.gz | |||
| SRR13084596_2.fastq.gz | Fastqsanger.gz | |||
| SRR13084597_1.fastq.gz | Fastqsanger.gz | |||
| SRR13084597_2.fastq.gz | Fastqsanger.gz | |||
| SRR13084599_1.fastq.gz | Fastqsanger.gz |
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Project description:Vascular endothelial and hematopoietic cells hold a close relationship that is initiated during development, but that continuously broadens to include new functions aimed at maintaining homeostasis in the adult organism. Here, we report on a population of aortic intimal resident macrophages (MacAIRs) that is a permanent feature of the inner vessel wall (tunica intima) of the aorta in regions of turbulent flow and that shares the luminal surface with the endothelium. MacAIRs were found to be transcriptionally distinct from other macrophages and closely associated with the endothelium in the absence of pathology. Lineage tracing analysis indicated that adult MacAIRs were derived from definitive hematopoietic lineage precursors that migrated from the ductus arteriosus seeding the aorta immediately post-birth in areas of turbulent flow including the lesser curvature of the aortic arch and branch openings. These aortic resident macrophages expanded via direct cell renewal and continued to grow in aged aortae to also populate regions of laminar flow. Binding of MacAIRs relied heavily on expression of endothelial ICAM that interacts with CD11c on macrophages. Genetic deletion of CD11c significantly impaired anchorage of MacAIRs to the endothelium. To clarify the biological significance of this population of macrophages, we used a dual diphtheria toxin induced-depletion system that efficiently eliminated MacAIRs in adult mice. Utilizing this model, we found that absence of MacAIRs led to progressive fibrin accumulation and formation of microclots that, once dislodged, can cause blockade of vessels and organ failure. In fact, 40% of the animals with genetic-mediated depletion of MacAIRs died within 2 weeks post-depletion suggesting that these macrophages were required to clear fibrin deposits in regions of turbulent blood flow. These findings advance our knowledge of how vascular endothelial cells profit from this unique interaction with macrophages to control hemostasis, prevent intravascular clotting, and ensure vascular health.
2021-11-08 | GSE161787 | GEO
Project description:Purpose: To investigate the effects of high cholesterol diet on the intimal transcriptome related to atherosclerosis. Methods: 3-week-old LDLR-/- male mice were fed a high cholesterol or low cholesterol diet for 9 weeks. Intimal RNA was extracted by injecting Trizol into the aorta and collecting the flow through for further processing. Results: Mice fed a high cholesterol revealed upregulation in atherosclerosis and immune/inflammatory related genes.
2023-02-08 | GSE213303 | GEO
Project description:Purpose: To investigate the effects of paternal high cholesterol diet on the F1 intimal transcriptome related to atherosclerosis. Methods:Three-week-old male LDL Receptor-deficient (LDLR-/-) male mice were fed a low-cholesterol diet (LCD) or high-cholesterol diet (HCD) for 8 weeks and then mated with age-matched control LDLR-/- female mice to generate F1 offspring. F1 LDLR-/- mice were fed a LCD for 16 weeks. Intimal RNA was extracted by injecting Trizol into the aorta and collecting the flow through for further processing. Results: . Total RNA isolated from the F1 intima were then subjected for RNA-sequencing analysis and results show that paternal hypercholesterolemia led to upregulation of 147 genes in the intimal of F1 female mice, many of which are involved in immune and inflammatory pathways.
2024-10-08 | GSE251711 | GEO
Project description:We reported the cellular heterogeneity in the whole aorta (adventitial and medial/intimal layers).
2020-03-31 | GSE140811 | GEO
Project description:Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in portions of the entire aorta under physiological conditions. Methods and Results: Animal-specific WSS magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Hand2, trpc4 and slain2, and confirmed well-known ones, such as klf2 and BMP4. Three genes were further validated for protein , including Hand2, which showed higher expression in the endothelium in regions exposed to disturbed flow. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation. Microarray analysis of two distinct flow pattern regions were identified in the normal rat aorta. Tissue pieces from groups of five animals were pooled for each region giving total of 28 pools; 14 paired sample pools of high and low wall shear stress.
2012-12-24 | E-GEOD-40170 | biostudies-arrayexpress
Project description:Here we undertook a proteomic investigation of ascending aorta from New Zealand White rabbits after 10 weeks on a high (2% w/w) cholesterol diet (HCD, n=5) or control diet (n=5) in order to profile the proteomic changes in response to the HCD. Histology confirmed intimal thickening in the HCD group and LC-MS/MS analysis of individually obtained ascending aorta extracts labelled with isobaric (iTRAQ) tags led to identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p<0.05), 62 were elevated and five decreased in ascending aorta from HCD-fed rabbits compared to controls. Six proteins were selected for validation using Multiple Reaction Monitoring which confirmed the iTRAQ results.
2018-06-21 | PXD002345 | Pride
Project description:Purpose: To reveal the small RNA profiles in the intima using traditional and PANDORA-seq methods. Methods: 3-week-old LDLR-/- male mice were fed a high cholesterol or low cholesterol diet for 9 weeks. Intimal RNA was extracted by injecting Trizol into the aorta and collecting the flow through for further processing. Results: PANDORA-seq revealed an abundant amount of tsRNA and rsRNA that were undetected by traditional-seq. Importantly, PANDORA-seq revealed that many differentially regulated sncRNAs also undetected with traditional-seq.
2023-02-08 | GSE213304 | GEO
Project description:Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in portions of the entire aorta under physiological conditions. Methods and Results: Animal-specific WSS magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Hand2, trpc4 and slain2, and confirmed well-known ones, such as klf2 and BMP4. Three genes were further validated for protein , including Hand2, which showed higher expression in the endothelium in regions exposed to disturbed flow. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation.
2012-12-24 | GSE40170 | GEO
Project description:Recently, we have shown that disturbed flow caused by partial ligation of mouse carotid artery rapidly induces endothelial dysfunction and atherosclerosis within two weeks. To understand the molecular mechanisms by which disturbed flow induces atherosclerosis, we carried out genome-wide microarray study using endothelial RNAs isolated from the flow-disturbed left and the contralateral right common carotid artery (LCA and RCA) in C57BL/6 mice. Total intimal RNAs were obtained from LCA and RCA at 12hr and at 48hr post-ligation. Intimal RNAs from three LCAs or RCAs were pooled to obtain ~30ng total RNA.
2011-03-10 | E-GEOD-20741 | biostudies-arrayexpress
Project description:Background: Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood. Sphingosine-1-phosphate (S1P) is a lipid mediator that regulates immune cell trafficking by signaling via five G protein-coupled receptors (S1PRs). We investigated the role of S1P in the RTM of aortic intimal MCs. Methods: Intravenous injection of lipopolysaccharide (LPS) was used to model a systemic inflammatory stimulus that triggers RTM. CD11c+ intimal MCs in the lesser curvature of the ascending aortic arch were enumerated by en face confocal microscopy. Local gene expression was evaluated by transcriptomic analysis of microdissected intimal cells. Results: In wild-type C57BL/6 mice, LPS induced intimal cell expression of S1pr1, S1pr3, and sphingosine kinase 1 (Sphk1, a kinase responsible for S1P production). Pharmacological modulation of multiple S1PRs blocked LPS-induced RTM and modulation of S1PR1 and S1PR3 reduced RTM in an additive manner. Cre-mediated deletion of S1pr1 in MCs blocked LPS-induced RTM, confirming a role for myeloid-specific S1PR1 signaling. Global or hematopoietic deficiency of Sphk1 reduced plasma S1P levels, the abundance of CD11c+ MCs in the aortic intima and blunted LPS-induced RTM. In contrast, plasma S1P levels, the abundance of intimal MCs, and LPS-induced RTM were rescued in Sphk1-/- mice transplanted with Sphk1+/+ or mixed Sphk1 +/+ and -/- bone marrow. Stimulation with LPS increased endothelial permeability and intimal MC exposure to circulating factors such as S1P. Conclusions: Functional and expression studies support a novel role for S1P signaling in the regulation of LPS-induced RTM as well as the homeostatic maintenance of aortic intimal MCs. Our data provides insight into how circulating plasma mediators help orchestrate intimal MC dynamics.
2024-02-22 | GSE252674 | GEO