The effect of pressure on gene expression of blood and venous endothelial cells in humans
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237856 | GEO | 2023/08/28
REPOSITORIES: GEO
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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 number of heart failure (HF) patients is increasing. HF is frequently accompanied by kidney dysfunction and such organ failure is closely related. Recent investigations revealed that increased renal venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in HF patients; however, the underlying responsible mechanisms are unknown. We demonstrated that reduced blood flow speed in peritubular capillaries (PTCs) by renal congestion and upregulation of nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral renal congestion by coarctation of the inferior vena cava between renal veins. Intravital imaging highlighted the notable dilatation of PTCs and decreased renal blood flow speed in the congestive kidney. Renal damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes (PMNs) within PTCs was observed at the acute phase after injury. Pharmacological inhibition of NF-κB ameliorated renal congestion-mediated exacerbation of kidney injury. In vitro, adhesion of PMNs on the TNFα-stimulated endothelial cells was accelerated by perfusion of PMNs at a slower speed, which was cancelled by the inhibition of NF-κB signaling. Our study demonstrates the importance of slower blood flow accompanying activated NF-κB signaling in the congestive kidney in the exacerbation of renal injury. These mechanisms may explain how increased renal venous pressure in HF patients causes the deterioration of kidney dysfunction. Inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased renal venous pressure.
2024-02-16 | GSE166838 | GEO
Project description:Vascular compromise in microsurgical free flap transfers continues to present devastating outcomes in terms of flap failure and increased operating room costs. Current devices to detect early venous congestion have not become widely accepted because of insufficient sensitivity, incisiveness, or practicality. In our study, we developed a venous obstruction rat model in which the superficial inferior epigastric (SIE) vessels to the lower abdominal flaps was separated and artery or vein was ligated, and the flap reattached. Flaps were harvested 4 hours post-op. Total RNA was isolated and gene expression profiles were compared by Affymetrix Whole Genome 230 2.0. Flaps from groups of Venous or artery congestion (VC or AC, resp.) and sham operation group, were harvested and RNA extraction and hybridization on Affymetrix microarrays. Other controls including histology assays to assure comparable phenotype within groups.
2016-07-24 | E-GEOD-35270 | biostudies-arrayexpress
Project description:Six healthy male adults underwent RIPC, consisting of 3x5 min cycles of upper arm ischemia (inflating a blood pressure cuff to >200 mmHg) alternating with 3x5 min reperfusion (bp cuff deflated). Blood samples were collected at baseline and at 1 and 4 min into each reperfusion period. Plasma was isolated and the six reperfusion samples were pooled to one RIPC sample. Both baseline and RIPC samples were depleted, concentrated, trypsin digested, iTRAQ labeled and analyzed by LC and Orbitrap-MS where each RIPC sample was compared to the same individual's baseline sample.
2014-09-16 | PXD000605 | Pride
Project description:Vascular compromise in microsurgical free flap transfers continues to present devastating outcomes in terms of flap failure and increased operating room costs. Current devices to detect early venous congestion have not become widely accepted because of insufficient sensitivity, incisiveness, or practicality. In our study, we developed a venous obstruction rat model in which the superficial inferior epigastric (SIE) vessels to the lower abdominal flaps was separated and artery or vein was ligated, and the flap reattached. Flaps were harvested 4 hours post-op. Total RNA was isolated and gene expression profiles were compared by Affymetrix Whole Genome 230 2.0.
2016-07-24 | GSE35270 | GEO
Project description:RELEVANCE: Identifying early plasma protein biomarkers that predict the development of heart failure (HF) following myocardial infarction (MI) will help to stratify at risk subjects and provide insight into more effective therapeutic strategies. OBJECTIVE/HYPOTHESIS: The goal of this study was to determine markers of HF in African Americans, using plasma samples collected before the development of symptoms. We propose that early plasma glycoprotein changes will link to later development of heart failure. ApolipoproteinF will be the strongest indicator. METHODS: Plasma samples from a subset of Jackson Heart Study participants with a history of MI but without prevalent heart failure (HF) at visit 2 (2005-2008) were analyzed by glycoproteomics. Individuals were grouped into those who experienced subsequent HF hospitalization after visit 2 (n=15; 3 men/ 12 women) and those without HF hospitalization through 2012 (n=45; 24 men/ 21 women). N-linked plasma glycopeptides were quantified by solid-phase extraction coupled to mass spectrometry and identified using RefSeq and SwissProt. Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis (IPA) and linked to clinical characteristics.
2018-08-30 | PXD009870 | Pride
Project description:Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury.
2024-11-06 | PXD043481 | Pride
Project description:Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodeling. Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. CITE-Seq analysis of cardiac immune cells reveals an altered abundance and/or transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including upregulation of Trem2, which was also recently implicated in obesity and atherosclerosis. The role of macrophage Trem2 in cardiac remodeling, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls, and Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programs. Furthermore, we found that plasma levels of soluble TREM2 are elevated in human heart failure. Together, our data suggest a novel cardioprotective role for macrophage Trem2 in cardiac remodeling and heart failure and provide an atlas for the identification of additional targets that can lead to improved diagnostic and therapeutic strategies for HFpEF.
2023-05-01 | GSE211166 | GEO
Project description:The aim of the present study was to examine potential differences in the regulation of myocardial ECM constituents, in mice that develop hypertrophy only (ABnonHF) and in mice that develop overt heart failure (ABHF) as response to pressure overload. Seven weeks old male C57BL/6 mice were subjected to aortic banding (AB) or sham operation (sAB), with sacrifice 4 weeks after banding. Prior to sacrifice, cardiac function and geometry were evaluated by echocardiography. Animals with comparable gradients over the banded ascending aorta, comparable cardiac output and heart rate were divided into two groups: ABnonHF and ABHF. Our criterion for dividing AB animals into these two groups was based on lung weight and left atrial diameter (LAD), as an increase in these parameters most likely is due to pulmonary congestion. Heart failure (HF) was defined as an increase in lung weight and LAD defining ABnonHF as lung weight/tibia length M-bM-^IM-$ 10.5 mg/mm and LAD M-bM-^IM-$ 2.0 mm and ABHF as lung weight/tibia length M-bM-^IM-% 15 mg/mm and LAD M-bM-^IM-% 2.4 mm. Microarray screening was performed in 7 mice from each AB group and in 5 sAB mice. Sham was used as control.
2012-11-01 | E-GEOD-36074 | biostudies-arrayexpress