Shimizu Nobuyuki, Suzuki Hiroshi, Wakabayashi Kohei, Iso Yoshitaka, Shibata Masayuki, Yorozuya Minoru, Katagiri Takashi, Takeyama Youichi
Department of Internal Medicine, Division of Cardiology, Showa University, Fujigaoka Hospital, Yokohama.
J Cardiol. 2004 Mar;43(3):131-9.
Restenosis after coronary intervention usually occurs due to coronary remodeling or neointimal formation, but inflammation is also important especially after stent implantation. Adhesion molecules are important in the recruitment of inflammatory cells into the neointima and in the phenotypical changes of vascular smooth muscle cells. To examine the role of adhesion molecules in the pathogenesis of restenosis, immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was investigated in the pig coronary injury model.
Left anterior descending coronary arteries of pigs were injured using a balloon. Two weeks after the injury, balloon injury was performed again in the balloon group and a Palmaz-Schatz stent was implanted in the stent group. Pigs were sacrificed at 1, 2 and 4 weeks. Immunohistochemical analysis was performed using ICAM-1, VCAM-1, macrophage and alpha-smooth muscle actin antibodies.
In non-injured vessels, weak immunoreactivities of ICAM-1 and VCAM-1 were observed in the endothelium and media. In injured sites, ICAM-1 and VCAM-1 were found in the inflammatory cells and smooth muscle cells in the neointima from 1 week, and strong immunoreactivities were seen around the strut in the stent group. Although the immunoreactivities peaked at 2 weeks in the balloon group, strong immunoreactivities were still seen at 4 weeks in the stent group. Regenerated endothelial cells were positive for both antibodies from 2 weeks.
The expression of ICAM-1 and VCAM-1 lasted longer in the stent group than in the balloon group, suggesting the occurrence of late restenosis after stent implantation. Control of the inflammatory response including adhesion molecules is essential for further reduction of restenosis after stent implantation.
冠状动脉介入术后再狭窄通常是由于冠状动脉重塑或新生内膜形成所致，但炎症也很重要，尤其是在支架植入后。黏附分子在炎症细胞募集到新生内膜以及血管平滑肌细胞表型变化中起重要作用。为研究黏附分子在再狭窄发病机制中的作用，在猪冠状动脉损伤模型中研究了细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的免疫组化表达。
用球囊损伤猪的左前降支冠状动脉。损伤后两周，球囊组再次进行球囊损伤，支架组植入Palmaz-Schatz支架。在1、2和4周时处死猪。使用ICAM-1、VCAM-1、巨噬细胞和α-平滑肌肌动蛋白抗体进行免疫组化分析。
在未损伤的血管中，在内皮和中膜观察到ICAM-1和VCAM-1的弱免疫反应性。在损伤部位，从第1周起在新生内膜的炎症细胞和平滑肌细胞中发现ICAM-1和VCAM-1，在支架组的支架周围可见强免疫反应性。虽然球囊组的免疫反应性在2周时达到峰值，但支架组在4周时仍可见强免疫反应性。从第2周起，再生的内皮细胞对两种抗体均呈阳性。
ICAM-1和VCAM-1的表达在支架组比在球囊组持续时间更长，提示支架植入后发生晚期再狭窄。控制包括黏附分子在内的炎症反应对于进一步降低支架植入后的再狭窄至关重要。
