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| Status |
Public on Dec 04, 2013 |
| Title |
Acute venous hypertension induces local release of inflammatory cytokines and endothelial activation in humans |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Colombo PC, Onat D, Harxhi A, Demmer RT, Hayashi Y, Jelic S, LeJemtel TH, Bucciarelli L, Kebschull M, Papapanou PN, Uriel N, Schmidt AM, Sabbah HN, Jorde UP |
| Citation(s) |
24265434 |
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| Submission date |
Jun 18, 2012 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Ryan T Demmer |
| E-mail(s) |
rtd2106@columbia.edu
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| Organization name |
Columbia University
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| Department |
Epidemiology
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| Street address |
722 W 168th St.
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (24)
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| GSM949418 |
Endothelial cell at T1, patient 2 |
| GSM949419 |
Endothelial cell at T0, patient 3 |
| GSM949420 |
Endothelial cell at T1, patient 3 |
| GSM949421 |
Endothelial cell at T0, patient 4 |
| GSM949422 |
Endothelial cell at T1, patient 4 |
| GSM949423 |
Endothelial cell at T0, patient 5 |
| GSM949424 |
Endothelial cell at T1, patient 5 |
| GSM949425 |
Endothelial cell at T0, patient 6 |
| GSM949426 |
Endothelial cell at T1, patient 6 |
| GSM949427 |
Endothelial cell at T0, patient 7 |
| GSM949428 |
Endothelial cell at T1, patient 7 |
| GSM949429 |
Endothelial cell at T0, patient 8 |
| GSM949430 |
Endothelial cell at T1, patient 8 |
| GSM949431 |
Endothelial cell at T0, patient 9 |
| GSM949432 |
Endothelial cell at T1, patient 9 |
| GSM949433 |
Endothelial cell at T0, patient 10 |
| GSM949434 |
Endothelial cell at T1, patient 10 |
| GSM949435 |
Endothelial cell at T0, patient 11 |
| GSM949436 |
Endothelial cell at T1, patient 11 |
| GSM949437 |
Endothelial cell at T0, patient 12 |
| GSM949438 |
Endothelial cell at T1, patient 12 |
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| Relations |
| BioProject |
PRJNA168633 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38783_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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