Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Isolation and immortalization of human portal vein endothelial cells: a novel research tool for investigating splanchnic vasculature

ABSTRACT: Cirrhosis profoundly impacts extrahepatic vasculature, particularly altering the portal venous system (PVS), leading to increased portal pressure, portosystemic collaterals, and portal vein thrombosis, which heightens morbidity and reduced survival in patients with liver disease. Despite extensive research on intrahepatic vasculature in cirrhosis, understanding of extrahepatic changes in the splanchnic territory at the molecular level remains limited. The distinct characteristics of the PVS suggest a unique endothelial profile crucial for elucidating vascular dysfunction in liver diseases. However, current research is hampered by the inaccessibility of the portal vein and imperfect preclinical models. Here, we aim to isolate and immortalize primary human portal vein endothelial cells (hPVECs) to enhance understanding of pathophysiological changes during liver disease and establish a platform for future drug testing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296600 | GEO | 2025/12/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Gut microbiota in cirrhosis and extrahepatic portal vein obstruction

| PRJNA1208993 | ENA

Endothelial-to-mesenchymal transition: A targetable mechanism that contributes to portal vein thrombosis in cirrhosis

Project description:Portal vein thrombosis (PVT) is a prevalent thrombotic complication in cirrhosis, yet its pathophysiology remains elusive, hindering effective treatment strategies. Unlike thrombosis in other vascular beds, anticoagulation often fails to achieve complete recanalization in PVT, highlighting the need of alternative therapeutic approaches. We investigated portal vein endothelium involvement in PVT pathogenesis, identifying potential therapeutic targets. We isolated for the first time primary human portal vein endothelial cells (PVEC) from explanted livers of cirrhotic patients with and without PVT, as well as from a control group without portal hypertension and conducted RNA sequencing. Transcriptomic analysis unveiled endothelial-to-mesenchymal transition (EndMT) pathway as a key mechanism underlying PVT in cirrhosis, predominantly induced through TGFβ/SMAD mechanism. Remarkably, coagulation markers remained unaffected. In silico drug repurposing identified statins as potential agents targeting these alterations. Our study elucidates significant endothelial changes in the portal vein of cirrhotic patients, particularly pronounced in those with PVT, with EndMT emerging as a pivotal process. Simvastatin emerges as a promising therapeutic option for PVT treatment and prevention by modulating EndMT in PVEC.

2025-12-02 | GSE261883 | GEO

Proteomics and Metabolomics based analysis of Metabolic changes in a swine model of Pulmonary Hypertension

Project description:Pulmonary vein stenosis (PVS) is a rare type of Pulmonary Hypertension (PH), which impacts the flow and pressure within the lung tissue and vasculature resulting in endothelial dysfunction and metabolic changes. We used a pig model in order to mimic PH post PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to investigate the alteration of pressure and flow which provides an impetus for development of PH. In order to develop site-specific therapies, our current study aimed to employ proteomics and metabolomics on both the upper and lower lobes of the pig lung to identify compartment-specific metabolic alterations.

2023-04-20 | PXD038982 | Pride

Portal Hypertension Induced Changes in Splenic Gene Expression

Project description:Splenomegaly is caused by several pathological conditions, including portal hypertension, which is most frequently caused by chronic liver disease (e.g., liver cirrhosis). The detailed mechanisms through which portal pressure induces splenomegaly and the precise pathophysiological conditions in portal hypertension-induced splenomegaly remain to be fully elucidated. We used microarrays to identify the differential gene expression underlying the portal hypertension-induced splenomegaly.

2018-11-21 | GSE113613 | GEO

Portal Hypertension Induced Changes in Splenic microRNA Expression

Project description:Splenomegaly is caused by several pathological conditions, including portal hypertension, which is most frequently caused by chronic liver disease (e.g., liver cirrhosis). The detailed mechanisms through which portal pressure induces splenomegaly and the precise pathophysiological conditions in portal hypertension-induced splenomegaly remain to be fully elucidated. We used microarrays to identify the differential microRNA expression underlying the portal hypertension-induced splenomegaly.

2018-11-21 | GSE113612 | GEO

Transcription profiling of rat cirrhotic liver treated with angiogenesis inhibitors

Project description:Background and aims: There are considerable evidences demonstrating that angiogenesis and chronic inflammation are mutually dependent. However, although cirrhosis progression is characterized with a chronic hepatic inflammatory process, this connection is not sufficiently explored as a therapeutic strategy. Therefore, this study was aimed to assess the potential benefits of targeting angiogenesis in cirrhotic livers to modulate inflammation and fibrosis. For this purpose, we evaluate the therapeutic utility of angiogenesis inhibitors. Methods: The in vivo effects of angiogenesis inhibitors were monitored in liver of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, a-smooth muscle actin (a-SMA) accumulation, differential gene expression (by microarrays), and portal pressure. Results: Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1, angiopoietin-2 and placental growth factor (PlGF) in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Interestingly, the expression of these adhesion molecules correlated well with local inflammatory infiltrate. Livers of cirrhotic rats treated with angiogenesis inhibitors presented a significant decrease in hepatic vascular density, inflammatory infiltrate, a-SMA abundance, collagen expression and portal pressure. Conclusion: Angiogenesis inhibitors may offer a potential novel therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation and fibrosis in cirrhotic livers. Experiment Overall Design: RNA from liver of 4 non-treated cirrhotic rats or 4 rats treated with angiogenesis inhibitors was hybridized to 8 high-density oligonucleotide microarray (Rat2302, Affymetrix, Santa Clara, CA)

2008-06-15 | E-GEOD-6929 | biostudies-arrayexpress

Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension

Project description:Persistent liver injury triggers a fibrogenic program that causes pathologic remodelling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and regression remain understudied. Here, we generated hepatic transcriptome profiles in two well-established liver disease models at peak fibrosis and during spontaneous regression after the removal of the inducing agents. We linked the dynamics of key liver disease readouts, such as portal pressure, collagen proportionate area, and transaminase serum levels, to most differentially expressed genes, enabling the identification of transcriptomic signatures of progressive vs. regressive liver fibrosis and portal hypertension. These candidate biomarkers (e.g., Scube1, Tcf4, Src, Hmga1, Trem2, Mafk, Mmp7) were also validated in RNA-seq datasets of patients with cirrhosis and portal hypertension. Finally, deconvolution analysis identified major cell types and suggested an association of macrophage and portal hepatocyte signatures with portal hypertension and fibrosis area in both models.

2024-02-13 | E-MTAB-13804 | biostudies-arrayexpress

Angiogenesis inhibitors ameliorates inflammatory infiltrate, fibrosis and portal pressure in cirrhotic rats

Project description:Background and aims: There are considerable evidences demonstrating that angiogenesis and chronic inflammation are mutually dependent. However, although cirrhosis progression is characterized with a chronic hepatic inflammatory process, this connection is not sufficiently explored as a therapeutic strategy. Therefore, this study was aimed to assess the potential benefits of targeting angiogenesis in cirrhotic livers to modulate inflammation and fibrosis. For this purpose, we evaluate the therapeutic utility of angiogenesis inhibitors. Methods: The in vivo effects of angiogenesis inhibitors were monitored in liver of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, a-smooth muscle actin (a-SMA) accumulation, differential gene expression (by microarrays), and portal pressure. Results: Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1, angiopoietin-2 and placental growth factor (PlGF) in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Interestingly, the expression of these adhesion molecules correlated well with local inflammatory infiltrate. Livers of cirrhotic rats treated with angiogenesis inhibitors presented a significant decrease in hepatic vascular density, inflammatory infiltrate, a-SMA abundance, collagen expression and portal pressure. Conclusion: Angiogenesis inhibitors may offer a potential novel therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation and fibrosis in cirrhotic livers. Keywords: angiogenesis, cirrhosis, liver, Affymetrix, fibrosis

2007-10-18 | GSE6929 | GEO

Identification of a portal vessel-associated fetal liver hematopoietic stem cell niche

Project description:Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation. Characterization of the transcriptome of fetal liver and adult bone marrow niche using RNA-seq

2015-12-03 | E-GEOD-72341 | biostudies-arrayexpress

Project description:Potential contribution of the gut microbiota in the development of Portal vein thrombosis in liver cirrhosis

| PRJNA967488 | ENA