Coronary Artery Proliferation and Remodeling after Coronary Artery Stenting and Directional Coronary Atherectomy

Lee, Dong Chea; Jeong, Myung Ho; Park, Ok Young; Kim, Weon; Kim, Kun Hyung; Cho, Jeong Gwan; Park, Jong Chun; Ahn, Byoung Hee; Kim, Sang Hyung; Kang, Jung Chaee; Schwartz, Robert S

Abstract

Coronary restenosis is a major concern in the field of interventional cardiology. Clinical trials for the prevention and treatment of coronary restenosis are focusing on atherectomy and stent, but the results are not promising in reducing the frequency of restenosis. The purpose of this study is the understanding the cell kinetics over time in cell proliferation following coronary stenting and directional coronary atherectomy in porcine coronary arteries. In porcine coronary models, Wiktor stent and directional coronary atherectomy (DCA) were performed in different major coronary arteries in the same animals. About 30% of overdilation injury was made by Wiktor stent and directional atherectomy in 12 animals. Histologic and immunopathologic analysis were performed at 7, 14 and 28 days after stent and DCA. Neointimal area after DCA was not changed significantly at 7, 14 and 28 days, but the neointimal area was significantly increased at 28 days after stenting (0.84+/-.21 mm2 at 7 days, 0.45+/-.10 mm2 at 14 days, 1.8+/-.23 mm2 at 28 days; p<0.05 for 28 days vs. 7 and 14 days). Cell densities of DCA and stent injury were not changed significantly at 7, 14 and 28 days. PCNA indices were 9.4+/-.3% at 7 days, 6.2+/-.9% at 14 days and 2.0+/-.1% at 28 days (p<0.05: 7 days vs. 14 days, 14 days vs. 28 days). PCNA indices of skin and intestine were 15+/-.2% and 20+/-.8%, which were significantly higher than that of coronary artery. In stented artery, the relationship between changes of external elastic lamina and neointimal area changes were well maintained (r=0.70, p=0.016), but in atherectomy arteries there were no relationship between both indices. Proliferation of coronary cells after stenting is more active in early phase than in late phase, but early proliferation of coronary cells was less active than normal skin and intestine. Stent injury induces beneficial remodeling. These results suggest that cell proliferation is important in the early phase of restenosis and that extracellular matrix production or aptosis is important in late restenosis.