Sus scrofa
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA98423 | ENA |
REPOSITORIES: ENA
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Project description:A porcine aortic coarctation model was used to examine regulation of gene expression in early hypertensive vascular remodeling. Aortic segments were collected proximal (high pressure) and distal (low pressure) to the coarctation after 2 weeks of sustained hypertension (mean arterial pressure>150mmHg). Porcine 10K oligoarrays used for gene expression profiling of the two regions of aorta revealed downregulation of cytoskeletal and upregulation of extracellular region genes relative to the whole genome. A genomic database search for transforming growth factor-β (TGFβ) control elements (TCE) showed that 19% of the genes that changed expression due to hypertension contained putative TCEs. Real time PCR and microarray analysis showed no change in expression of TGFβ1, TGFβ2, TGFβ3, or bone morphogenetc proteins (BMP)2 and 4, yet immunohistochemical staining for phosphorylated SMAD2, an indicator of TGFβ signaling, and for phosphorylated SMAD1/5/8, an indicator of signaling through the BMPs, showed the highest percentage of positively stained cells in the proximal aortic segments of occluded animals. For TGFβ signaling, this increase was significantly different from sham-operated controls. Western blot analysis showed no difference in total TGFβ1 protein levels with respect to treatment or aortic segment. Immunohistochemistry showed that the protein levels of latency associated peptide, was decreased in proximal segments of occluded animals. Collectively, these results suggest that activation of TGFβ, but not altered expression, may be a major mechanism regulating early hypertensive vascular remodeling.
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