Assessment of subacute inflammatory and proliferative response to coronary stenting in a porcine model by local gene expression studies and histomorphometry

The aim of the study was to analyse inflammatory and proliferative response early after coronary stenting by angiography, histomorphometry and local gene expression analysis using quantitative rt-PCR. Therefore, eight German domestic pigs underwent stenting of the left coronary artery. Selective coronary angiography was performed after 14 days. Explanted coronary arteries were examined histomorphometrically after methacrylate-embedding. Snap-frozen samples were examined for local gene expression of TGF-beta, TNF-alpha, GM-CSF, VEGF, PDGF and Fas Ligand (FasL) by real-time quantitative rt-PCR normalized to the housekeeping gene GAPDH and compared to unstented coronary arteries. All stented coronaries were patent with only little neointima formation. The median vessel diameter was 2.55 mm (range 2.43-2.68 mm). Histopathology revealed little inflammatory response limited to the tissue surrounding the stent struts; luminal area ranged from 84% to 91%. Compared to unstented control arteries, no significant differences in local gene expression were detected for VEGF, PDGF, TGF-beta, TNF-alpha and GM-CSF. Expression of FasL was upregulated as little as 1.7-fold (p=0.01). We conclude that, in native coronary arteries, no significant upregulation of investigated genes regulating vascular remodelling, inflammation or fibrogenesis was demonstrated 14 days after stenting. Whether upregulation of FasL as a marker gene of apoptosis is transient and biological significant requires further investigation.