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| Status |
Public on May 03, 2011 |
| Title |
Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Data from clinical studies, cell culture, and animal models implicate the urokinase (uPA)/Plasminogen (Plg) system in the development of atherosclerosis and aneurysms. However, the mechanisms through which uPA/Plg stimulate these diseases are not yet defined. We used genetically modified, atherosclerosis-prone mice, including mice with macrophage-specific uPA overexpression to clarify mechanisms of uPA/Plg-accelerated atherosclerosis and aneurysm formation. Microarray studies were performed to identify potential mediators of uPA-accelerated atherosclerosis. These studies identified S100A8 and S100A9 mRNA as the most highly upregulated transcripts in uPA-overexpressing macrophages; upregulation of S100A9 protein in uPA-overexpressing macrophages was confirmed by Western blotting. S100A8/A9, which are atherogenic in mice and are expressed in human atherosclerotic plaques, are also upregulated in aortae of mice with uPA-overexpressing macrophages, and macrophage S100A9 mRNA is upregulated by exposure of wild-type macrophages to medium from uPA-overexpressing macrophages. Bioinformatics analysis of the microarray data suggest significant effects of uPA overexpression on cell migration and cell-matrix interactions. Our results confirm—in a second animal model—that macrophage-expressed uPA stimulates atherosclerosis and aortic dilation. They also implicate specific pathways in uPA/Plg-accelerated atherosclerosis and aneurysmal disease.
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| Overall design |
Six independent biological replicate RNA samples were prepared from thioglycollate-elicited peritoneal macrophages from mice of two different genotypes: SR-uPA+/0 transgenic (overexpress uPA in macrophages) and nontransgenic, respectively), for a total of 12 independent RNA samples. Both transgenic and nontransgenic mice were Apoe-/- and were fed Western diet from 5-15 weeks before peritoneal macrophages were elicited. In addition, from the six samples of each genotype, a pooled sample was prepared by combining the six genotype-specific samples. Each of the two pooled samples was assayed on the BeadChip in two technical replicates, for a total of 16 hybridizations performed using two Illumina Mouse Ref-8 v1.1 chips.
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| Contributor(s) |
Farris SD, Hu JH, Krishnan R, Emery I, Chu T, Du L, Kremen M, Dichek HL, Gold ES, Ramsey SA, Dichek DA, Amon L |
| Citation(s) |
21536666 |
| Submission date |
May 03, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Jie Hong Hu |
| E-mail(s) |
jhhu@u.washington.edu
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| Phone |
206-616-4232
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| Fax |
206-221-6346
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| Organization name |
University of Washington
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| Department |
Medicine
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| Lab |
David Dichek
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| Street address |
1959 NE Pacific St, HSB K-127
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98195 |
| Country |
USA |
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| Platforms (1) |
| GPL7868 |
VUmc/Illumina Sentrix MouseRef8 v1.1 |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA140485 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29028_non-normalized_data.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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