Transforming growth factor-β signaling in hypertensive remodeling of porcine aorta

Natasa Popovic, Eric A. Bridenbaugh, Jessemy D. Neiger, Jin Jia Hu, Marina Vannucci, Qianxing Mo, Jerome Trzeciakowski, Matthew W. Miller, Theresa W. Fossum, Jay D. Humphrey, Emily Wilson

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19 引文 斯高帕斯(Scopus)


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 wk of sustained hypertension (mean arterial pressure > 150 mmHg). 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 (TGF-β) control elements showed that 19% of the genes that changed expression due to hypertension contained putative TGF-β control elements. Real-time RT-PCR and microarray analysis showed no change in expression of TGF-β1, TGF-β2, TGF-β3, or bone morphogenetic proteins-2 and -4, yet immunohistochemical staining for phosphorylated SMAD2, an indicator of TGF-β signaling, and for phosphorylated SMAD1/5/8, an indicator of signaling through the bone morphogenetic proteins, showed the highest percentage of positively stained cells in the proximal aortic segments of occluded animals. For TGF-β signaling, this increase was significantly different than for sham-operated controls. Western blot analysis showed no difference in total TGF-β1 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 TGF-β, but not altered expression, may be a major mechanism regulating early hypertensive vascular remodeling.

頁(從 - 到)H2044-H2053
期刊American Journal of Physiology - Heart and Circulatory Physiology
出版狀態Published - 2009 12月

All Science Journal Classification (ASJC) codes

  • 生理學
  • 心臟病學與心血管醫學
  • 生理學(醫學)


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