The Effect of Vascular Wall Injury on the Regulation of Cell Cycle and Inflammation Marker Proteins
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The objective of this study was to investigate the effect of vascular wall injury through stent oversizing on the regulation of cell cycle proteins and inflammation markers. In particular, the amounts of cell cycle regulatory proteins, p27 and FKBP12, and inflammation marker, PCNA, were assessed in high injury, low injury and control treatment groups. Cypher© sirolimus eluting stents and Bx Velocity© (balloon expandable) bare metal stents were implanted in four Sus scrofa at high injury (30% balloon to artery ratio, or BAR), and in four swine at low injury (15% BAR). It was hypothesized that PCNA and FKBP12 would be upregulated and p27 would be downregulated in the high injury treatment group as compared to the low injury and control treatment groups. Arterial tissue samples were obtained from stented vessels and from non-stented control vessels, three days following stent implantation. Fallowing determination of protein concentration in the sample, SDS-PAGE and Western Blot analysis were performed. For statistical analysis, protein values were normalized initially to actin, as a loading control, and then to untreated (non-stented) controls, to account for variation among the pigs. No significant differences in p27 or PCNA expression were found among high injury, low injury or untreated models. For FKBP12, however, we found that as vessel wall trauma became more severe due to stent oversizing, the amount of FKBP 12 increased from 1.807±1.473 to 9.952±13.963 (p=0.0396). This suggests that high vessel wall injury leads to cell cycle hyperactivation and potentially contributes to increased intimal thickening.