A targetable pathway in neutrophils mitigates both arterial and venous thrombosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA859385 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20274801_1.fastq.gz | Fastqsanger.gz | |||
| SRR20274801_2.fastq.gz | Fastqsanger.gz | |||
| SRR20274802_1.fastq.gz | Fastqsanger.gz | |||
| SRR20274802_2.fastq.gz | Fastqsanger.gz | |||
| SRR20274803_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:Arterial and venous (A/V) thrombosis constitutes the greatest source of morbidity and mortality worldwide. Long considered as distinct entities, accumulating evidence indicates that A/V thrombosis can occur in the same populations suggesting that common mechanisms are likely operative. Although hyperactivation of the immune system is a common forerunner to the genesis of thrombotic events in both vascular systems, the key molecular control points remain poorly understood. Consequently, anti-thrombotic therapies targeting the immune system for therapeutic gain are lacking. Here we show that neutrophils are key effectors of both A/V thrombosis and can be targeted via novel immunoregulatory nanoparticles. Using antiphopholipid antibody syndrome (APS) as a model for devastating A/V thrombosis, we identified the transcription factor Krüppel-like factor 2 (KLF2) as a key regulator of neutrophil activation. Upon activation via genetic loss of KLF2 or administration of antiphospholipid antibodies, neutrophils cluster P-selectin glycoprotein ligand 1 (PSGL-1) via cortical actin remodeling, thereby increasing adhesion potential at thrombosis sites. Targeting clustered PSGL-1 using designer nanoparticles attenuates neutrophil-mediated A/V thrombosis in APS and KLF2 knockout models, illustrating the importance and feasibility of targeting activated neutrophils to prevent pathological thrombosis. Together, our results demosntrate a role for activated neutrophils to prevent pathological thrombosis. Together, our results demonstrate a role for activated neutorphils in both arterial and venous thrombosis and identify key molecular events that serve as potential targets for therapeutics against diverse causes of immunothrombosis.
2022-09-12 | GSE208336 | GEO
Project description:GENEVA GWAS of Venous Thrombosis
| PRJNA75937 | ENA
Project description:Arterial and venous thrombosis constitutes a major source of morbidity and mortality worldwide. Long considered as distinct entities, accumulating evidence indicates that arterial and venous thrombosis can occur in the same populations, suggesting that common mechanisms are likely operative. Although hyperactivation of the immune system is a common forerunner to the genesis of thrombotic events in both vascular systems, the key molecular control points remain poorly understood. Consequently, antithrombotic therapies targeting the immune system for therapeutics gain are lacking. Here, we show that neutrophils are key effectors of both arterial and venous thrombosis and can be targeted through immunoregulatory nanoparticles. Using antiphospholipid antibody syndrome (APS) as a model for arterial and venous thrombosis, we identified the transcription factor Krüppel-like factor 2 (KLF2) as a key regulator of neutrophil activation. Upon activation through genetic loss of KLF2 or administration of antiphospholipid antibodies, neutrophils clustered P-selectin glycoprotein ligand 1 (PSGL-1) by cortical actin remodeling, thereby increasing adhesion potential at sites of thrombosis. Targeting clustered PSGL-1 using nanoparticles attenuated neutrophil-mediated thrombosis in APS and KLF2 knockout models, illustrating the importance and feasibility of targeting activated neutrophils to prevent pathological thrombosis. Together, our results demonstrate a role for activated neutrophils in both arterial and venous thrombosis and identify key molecular events that serve as potential targets for therapeutics against diverse causes of immunothrombosis.
| S-EPMC10318551 | biostudies-literature
Project description:Background: Deep venous thrombosis is one of the most common peripheral vascular diseases that lead to major morbidity and mortality. We aimed to identify potential differentially expressed miRNAs and target mRNAs, which were helpful in understanding the potential molecule mechanism of deep venous thrombosis.
2025-02-01 | GSE196751 | GEO
Project description:Formation and maturation of a functional blood vascular system is required for the development and maintenance of all tissues in the body. During the process of blood vessel development, primordial endothelial cells are formed and become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues. Specification of arterial and venous endothelial cells occurs in conjunction with suppression of endothelial cell cycle progression, and endothelial cell hyperproliferation is associated with potentially lethal arterial-venous malformations. However, the mechanistic role that cell cycle state plays in arterial-venous specification is unknown. Herein, studying vascular development in Cdh5-CreERT2;R26FUCCI2aR reporter mice, we find that venous and arterial endothelial cells exhibit a propensity for different cell cycle states during development and in adulthood. That is, venous endothelial cells are predominantly FUCCI-Negative, while arterial endothelial cells are enriched for the FUCCI-Red reporter. Single cell RNA sequencing analysis of developing retinal endothelial cells reveals that venous endothelial cells are enriched for the FUCCI-Negative state and BMP signaling, while arterial endothelial cells are enriched for the FUCCI-Red state and TGF-b signaling. Further transcriptional analyses and live imaging of cultured endothelial cells expressing the FUCCI reporter show that reporter-negative corresponds to an early G1 state and reporter-red corresponds to late G1 state. We find the early G1 state is essential for BMP4-induced venous gene expression, whereas late G1 state is essential for TGF-b1-induced arterial gene expression. In a mouse model of endothelial cell hyperproliferation and disrupted arterial-venous specification, pharmacological inhibition of endothelial cell cycle prevents the vascular defects. Collectively, our results show that endothelial cell cycle control plays a key role in arterial-venous network formation, and distinct cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous specification.
2022-08-22 | GSE211658 | GEO
Project description:Formation and maturation of a functional blood vascular system is required for the development and maintenance of all tissues in the body. During the process of blood vessel development, primordial endothelial cells are formed and become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues. Specification of arterial and venous endothelial cells occurs in conjunction with suppression of endothelial cell cycle progression, and endothelial cell hyperproliferation is associated with potentially lethal arterial-venous malformations. However, the mechanistic role that cell cycle state plays in arterial-venous specification is unknown. Herein, studying vascular development in Cdh5-CreERT2;R26FUCCI2aR reporter mice, we find that venous and arterial endothelial cells exhibit a propensity for different cell cycle states during development and in adulthood. That is, venous endothelial cells are predominantly FUCCI-Negative, while arterial endothelial cells are enriched for the FUCCI-Red reporter. Single cell RNA sequencing analysis of developing retinal endothelial cells reveals that venous endothelial cells are enriched for the FUCCI-Negative state and BMP signaling, while arterial endothelial cells are enriched for the FUCCI-Red state and TGF-b signaling. Further transcriptional analyses and live imaging of cultured endothelial cells expressing the FUCCI reporter show that reporter-negative corresponds to an early G1 state and reporter-red corresponds to late G1 state. We find the early G1 state is essential for BMP4-induced venous gene expression, whereas late G1 state is essential for TGF-b1-induced arterial gene expression. In a mouse model of endothelial cell hyperproliferation and disrupted arterial-venous specification, pharmacological inhibition of endothelial cell cycle prevents the vascular defects. Collectively, our results show that endothelial cell cycle control plays a key role in arterial-venous network formation, and distinct cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous specification.
2022-08-28 | GSE211958 | GEO
Project description:The vascular tree has considerable diversity, with discrete regions having different physiologic characteristics and permeability. Of note are venules that are significantly more sensitive to pro-inflammatory cytokines than arterioles. We used microarrays to identify molecular signatures that distinguish primary human venous endothelial cells from arterial endothelial cells. We used microarrays to identify genes differentially expressed by venous vs arterial human endothelial cells.
2021-01-18 | GSE137041 | GEO
Project description:Circulating microRNAs (miRNAs) presented in venous plasma have recently been demonstrated as powerful biomarkers for the diagnosis and prognostic prediction of complex diseases like cancer. Nevertheless, those presented in arterial plasma have been ignored based on the assumption that the miRNA profiles in arterial and venous plasma would be identical. Here, we disputed this intuitive assumption by comparing arterial and venous plasma miRNA expression profiles from male rats using microarray technique. Though the microRNA profiles were largely similar, a considerable number of miRNAs showed significant differential expression, including 10 arterial highly expressed miRNAs and 14 venous highly expressed miRNAs. The differentially expressed miRNAs were validated by qRT-PCR. We performed computational analysis of the function enrichment and disease association of these miRNAs and their targets. Our analysis also suggested significant correlations between plasma miRNA expression and tissue miRNA expression. Four arterial highly expressed miRNAs showed enriched expression in specific tissues and thus could serve as novel biomarker candidates.
2016-11-22 | GSE90098 | GEO
Project description:HUVEC-FUCCI cells were used to demonstrate that different endothelial cell cycle states provide distict windows of opportunity for gene expression in response to extrinsic signals. HUVEC-FUCCI were FACS-isolated into three different cell cycle states. Peptide digests from the resulting lysates showed differentially expressed proteins among the three cell cycles. These studies show that endothelial cell cycle state determines the propensity for arterial vs. venous fate specification.
2022-10-12 | PXD036326 | Pride
Project description:Recent advancements have identified numerous long non-coding RNAs (lncRNAs) involved in various biological processes and diseases. However, the roles of lncRNAs in venous thromboembolism (VTE) remain largely unexplored. This study aims to elucidate the expression profiles of lncRNAs and mRNAs in a well-established animal model of VTE. Acute thrombosis was induced by surgical ligation of the inferior vena cava (IVC) within 24 hours. The thrombus burden in venous vessels was evaluated using hematoxylin and eosin staining and Masson's trichrome staining. The IVC and associated thrombus were harvested 24 hours post-ligation, and the extracted RNA was subjected to RNA sequencing (RNA-seq) analysis. This study offers a comprehensive overview of the expression profiles of lncRNAs and mRNAs in a murine model of venous thrombosis, providing novel insights into the roles of RNAs in VTE.
2025-02-19 | GSE269352 | GEO