Homo sapiens
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PROVIDER: PRJNA168633 | ENA |
REPOSITORIES: ENA
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Project description:Background: Venous hypertension is often present in advanced and in acute decompensated heart failure (HF). However, it is unclear whether high intravenous pressure can cause alterations in homeostasis by promoting inflammation and endothelial cell (EC) activation. We used an experimental model of acute, local venous hypertension to study the changes in circulating inflammatory mediators and EC phenotype that occur in response to biomechanical stress. Methods and Results: Twenty-four healthy subjects (14 men, age 35±2 years) were studied. Venous arm pressure was increased to ~30 mmHg above baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 minutes of venous hypertension, using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. 5,332 probe sets were differentially expressed in venous ECs before vs. after testing. Among the 143 probe sets that exhibited a significant absolute fold change >2, we identified several inflammatory mediators including ET-1, VCAM-1, and CXCL2. Conclusions: Acute experimental venous hypertension is sufficient to cause local increase in circulating inflammatory mediators and to activate venous ECs in healthy human subjects. Additional work is needed to determine the effect of venous hypertension in patients with established HF. 24 samples were analyzed from 12 patients. Each patient contributed 2 samples (1 prior to intervention and 1 after intervention). The pre-intervention sample serves as the control.
2013-12-04 | E-GEOD-38783 | biostudies-arrayexpress
Project description:Background: Venous hypertension is often present in advanced and in acute decompensated heart failure (HF). However, it is unclear whether high intravenous pressure can cause alterations in homeostasis by promoting inflammation and endothelial cell (EC) activation. We used an experimental model of acute, local venous hypertension to study the changes in circulating inflammatory mediators and EC phenotype that occur in response to biomechanical stress. Methods and Results: Twenty-four healthy subjects (14 men, age 35±2 years) were studied. Venous arm pressure was increased to ~30 mmHg above baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 minutes of venous hypertension, using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. 5,332 probe sets were differentially expressed in venous ECs before vs. after testing. Among the 143 probe sets that exhibited a significant absolute fold change >2, we identified several inflammatory mediators including ET-1, VCAM-1, and CXCL2. Conclusions: Acute experimental venous hypertension is sufficient to cause local increase in circulating inflammatory mediators and to activate venous ECs in healthy human subjects. Additional work is needed to determine the effect of venous hypertension in patients with established HF.
2013-12-04 | GSE38783 | 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:Severe systemic inflammatory reactions, including sepsis, often lead to shock, organ failure and death, in part through an acute release of cytokines that promote vascular dysfunction. However, little is known about the vascular endothelial signaling pathways regulating the transcriptional profile in failing organs. Among all the cytokines altered during a cytokine storm, IL-6 levels are particularly informative, as they correlate with systemic disease severity and are highly predictive of mortality. Here, we show that loss of endothelial expression of the IL-6 pathway inhibitor, SOCS3, promotes a type I interferon (IFNI)-like gene signature in response to endotoxemia in mouse kidneys and brains. In cultured primary human endothelial cells, IL-6 induces a transient IFNI-like gene expression in a non-canonical, interferon-independent fashion. We further show that STAT3, which we had previously shown to control IL-6-driven endothelial barrier function, is dispensable for this activity. Instead, IL-6 promotes a transient increase in cytosolic mitochondrial DNA and requires STAT1, cGAS, STING, and the IRFs 1, 3, and 4. Inhibition of this pathway in endothelial-specific STING knockout mice or global STAT1 knockout mice leads to reduced severity of an acute endotoxemic challenge and prevents the endotoxin-induced IFNI-like gene signature. These results suggest that permeability and DNA sensing responses are driven by parallel pathways downstream of this cytokine, provide new insights into the complex response to acute inflammatory responses, and offer the possibility of novel therapeutic strategies for independently controlling the intracellular responses to IL-6 in order to tailor the inflammatory response.
2025-08-11 | GSE300619 | GEO
Project description:Study hypothesis: To compare standard surgical approach to minilaparotomy in patients undergoing surgical resection for colorectal cancer. Once group will have surgery in the conventional manner and the other will have it performed using a mini-laparotomy. A mini-laparotomy being where the incision, through which the abdominal cavity is entered to reach the cancer, is 15cm or less; whereas conventionally a cut is made along the entire length of the abdomen.
We aim to show that there is a reduced inflammatory response to the mini-laparotomies by measuring inflammatory markers (cytokines) from blood samples taken before and after surgery.
We believe that a reduced acute inflammatory response post surgery has benefits for the patient in both the short term with regards to improved recovery times to mobilisation and restoration of bowel function and the longer term with relation to rates of local recurrence of the tumour and overall prognosis.
Primary outcome(s): The primary outcome measure is the amount of acute inflammatory markers (the cytokines IL-6, IL-2, IL-1beta and TNF-alpha) measured from venous blood samples taken 1 day pre operation, day 1, day 5 and 2 months post surgery in the two groups.
| 2424569 | ecrin-mdr-crc
Project description:Acute lung injury (ALI) refers to a clinical syndrome characterized by bilateral lung injury, severe lung diffuse failure and hypoxemia caused by non-cardiogenic pulmonary edema.Sepsis is the leading etiology of ALI and a common admission to the intensive care unit, which induces pulmonary inflammation leading disruption of endothelial-epithelial barriers by surge release of pro-inflammatory cytokines that increases the permeability of the alveolar-capillary membrane, pulmonary infiltration, and edema.Ultimately, gas exchange across the alveolar-capillary membrane is severely impaired and acute respiratory failure and hypoxia occur. ALI patients may suffer from pulmonary inflammation and hypoxia simultaneously or sequentially, those two pathophysiological processes may interact mutually and contribute together to the development of ALI. LPS is the most important biological mediator of sepsis induce secretion of inflammatory cytokines including TNF-α, IL-1, and IL-6 from many cell types in response to bacterial toxins. Thus LPS has been commonly used to establish inflammatory ALI models of rats and mice. Clinically, hypoxia commonly coexists with sepsis; however, the role of hypoxia on the development of inflammatory ALI is unclear. The understanding of interaction of hypoxia and inflammation in ALI is of the importance for the treatment of ALI.
2018-08-21 | GSE111241 | GEO
Project description:Arterial and venous endothelial cells exhibit distinct molecular characteristics at early developmental stages. These lineage-specific molecular programs are instructive to the development of distinct vascular architectures and physiological conditions of arteries and veins, but their roles in angiogenesis remain unexplored. Here, we show that the caudal vein plexus in zebrafish forms by endothelial cell sprouting, migration and anastomosis, providing a venous-specific angiogenesis model. Using this model, we identified a novel compound, aplexone, which effectively suppresses venous, but not arterial, angiogenesis. Multiple lines of evidence indicate that aplexone differentially regulates arteriovenous angiogenesis by targeting the HMG-CoA reductase (HMGCR) pathway. Treatment with aplexone affects the transcription of enzymes in the HMGCR pathway and reduces cellular cholesterol levels. Injecting mevalonate, a metabolic product of HMGCR, reverses the inhibitory effect of aplexone on venous angiogenesis. In addition, aplexone treatment inhibits protein prenylation and blocking the activity of geranylgeranyl transferase induces a venous angiogenesis phenotype resembling that observed in aplexone-treated embryos. Furthermore, endothelial cells of venous origin have higher levels of proteins requiring geranylgeranylation than arterial endothelial cells and inhibiting the activity of Rac or Rho Kinase effectively reduces the migration of venous, but not arterial, endothelial cells. Taken together, our findings indicate that angiogenesis is differentially regulated by the HMGCR pathway via an arteriovenousdependent requirement for protein prenylation in zebrafish and human endothelial cells.
2011-01-11 | E-MTAB-494 | biostudies-arrayexpress
Project description:BACKGROUND: As evidenced by epidemiological and etiological studies, the development of varicose veins is driven by risk-factors which support the development of venous hypertension and thus chronically augment circumferential stress of the venous wall (e.g. dysfunctional venous valves, pregnancy or obesity). We have previously verified the relevance of this biomechanical stimulus for the activation of venous endothelial as well as smooth muscle cells and the subsequent detrimental structural remodeling of the vein wall in experimental mouse models. METHODS: Here, transcriptome analyses revealed an increase in the expression of cyclooxygenase 2 (COX-2) in human venous endothelial cells upon exposure to biomechanical stress. Subsequently, we investigated the impact of diclofenac – a cyclooxygenase inhibitor – on responses of isolated mouse veins to augmented wall stress in vitro and on varicose-like venous remodeling in vivo. RESULTS: Diclofenac treatment decreased COX-2 protein abundance in mouse veins but had no significant impact on the expression of corresponding transcripts. Short-term exposure to elevated pressure levels stimulated the activity of matrix-metalloproteinase-2 (MMP-2) and mitogen activated protein kinases ERK1/2. Diclofenac decreased the level of activated MMP-2 and ERK1/2 in pressure-exposed mouse veins. Varikose-like remodeling of veins in the mouse auricle was significantly inhibited by transdermal application of diclofenac-containing phospholipid-micelles. This effect was associated with decreased COX-2 and MMP-2 abundance as well as cell proliferation. CONCLUSION: The cyclooxygenase inhibitor diclofenac interferes with short term activation of MAP-kinases and matrix-metalloproteinases in cells of the wall stress-exposed venous wall while attenuating venous remodeling in vivo. Thus, nonsteroidal anti-inflammatory drugs may be suitable to interfere with processes promoting the progression of varicose vein development and biomechanical activation of venous cells.
2021-01-12 | GSE121557 | GEO
Project description:The secondary immune response to ischemic stroke progresses for days to weeks and involves glial and brain endothelium activation, recruitment of peripheral immune cells, and release of cytokines and chemokines. Whereas there is evidence that the acute inflammatory response contributes to the progression of ischemic brain injury, on the other hand, recent research points at a more multifaceted role of immune cells in brain ischemia, where immune cells participate in repair processes during the sub-acute and chronic stages. Here we used single-cell sequencing to gain deeper insights into the impact of ischemic stroke on signature and the heterogeneity of brain immune cells, endothelial cells and circulating leukocytes in mice.
2023-06-14 | GSE225948 | GEO
Project description:Intestinal edema induced by a combination of mesenteric venous hypertension and resuscitative fluids (RESUS+VH, E), control was sham operated (CONTROL, C), also included mesenteric venous hypertension only (VH, V) and resuscitative fluid administration only (RESUS, S); samples collected 6 hours after surgery. Keywords: disease state analysis
2008-12-01 | GSE13193 | GEO