Endothelial dysfunction and collagen accumulation - Two independent factors for restenosis and constrictive remodeling after experimental angioplasty

Background-Constrictive remodeling plays a prominent role in restenosis aft er balloon angioplasty, but its regulation remains unclear. Because endothe lial dysfunction and changes in extracellular matrix have been reported aft er angioplasty, this study was designed to simultaneously evaluate endothel ial function and collagen and elastin changes after restenosis and arterial remodeling. Methods and Results-Atherosclerosis was induced in femoral arteries of 22 N ew Zealand White rabbits by air-desiccation and a high-cholesterol diet. On e month later, angioplasty was performed. Histomorphometry and in vitro ass essment of endothelial function were performed 4 weeks after angioplasty. R estenosis correlated with constrictive remodeling (r=0.60, P=0.01) but not with neointimal growth (r=-0.06, P=0.79). Restenosis correlated with an imp aired relaxation to acetylcholine (ACh; r=0.61, P=0.02) but not with the re sponse to the endothelium-independent vasodilator sodium nitroprusside (r=- 0.25, P=0.40), Restenosis correlated positively with collagen accumulation (r=0.69, P=0.004) and inversely with elastin density (r=-0.48, P=0.05). Rel axations to ACh were significantly more decreased in arteries with constric tive remodeling than in those with enlargement remodeling (3.7+/-7.9% versu s 35.5+/-15.0%, P=0.04). Neointimal collagen density was significantly high er in arteries with constrictive remodeling than in those with enlargement remodeling (34.5+/-4.5% versus 18.2+-4.7%, P=0.03). Endothelial function an d collagen and elastin density were independent predictors of restenosis in the study. Conclusions-These results demonstrate that the severity of restenosis after angioplasty correlated with both defective endothelium-dependent relaxatio n and increased collagen density.