Transcriptomics

Dataset Information

0

Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE29028 | GEO | 2011/05/03

SECONDARY ACCESSION(S): PRJNA140485

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2011-05-03 | E-GEOD-29028 | biostudies-arrayexpress
2021-12-01 | GSE174796 | GEO
2024-11-06 | GSE265848 | GEO
2011-11-20 | E-GEOD-33768 | biostudies-arrayexpress
2023-05-10 | PXD030857 | Pride
2024-05-06 | GSE247260 | GEO
2011-11-20 | GSE33768 | GEO
2024-07-29 | GSE234287 | GEO
2021-01-01 | GSE155421 | GEO
2022-02-15 | PXD028363 | Pride