The Role of Extracellular Matrix within the Neointima in A Porcine Coronary Stent Restenosis Model

ABSTRACT

BACKGROUND AND OBJECTIVES: Coronary stent restenosis remains a major limitation to percutaneous coronary intervention. The most important mechanism of coronary stent restenosis is neointimal hyperplasia (NIH). In addition to neointimal cell proliferation, extracellular matrix (ECM) synthesis may be important in the induction of NIH. We sought to observe the degree of this in a porcine model. SUBJECTS AND METHODS: Twenty-one coronary stents were placed in 15 pigs, and the pigs were sacrificed at 14 (Group I), 28 (Group II) and 56 (Group III) days following stenting. The twenty-one coronary stents were classified into three groups, followed by histopathological analyses of 7 stented arteries. Each specimen was analyzed by H&E, modified Movat and Masson-Trichrome staining methods. Immunocytochemistry was performed for type I collagen, smooth muscle a-actin and proliferating cell nuclear antigen (PCNA). A Visus 2000 Visual Image Analysis System was used. RESULTS: There were no differences in the injury scores of the stented porcine coronary arteries between the three groups. The areas of neointima in Groups I, II and III were 0.75+/-0.32, 1.45+/-0.78 and 1.62+/-0.51 mm2, respectively (Group I vs. II and Group I vs. III ; p=0.08, p=0.03). The pathological area stenoses were 18.8+/-7.4, 34.2+/-0.2 and 43.1+/-28.4% in Groups I, II and III, respectively (Group I vs. II and Group I vs. III ; p=0.35, p=0.02). The PCNA indices of neointima were 16.5+/-14.4, 0.5+/-0.74 and 0.83+/-0.68% in Groups I, II and III, respectively (Group I vs. II and Group I vs. III ; p=0.01). The collagen content ratios within the neointima were 23.5+/-4.7, 27.7+/-5.0 and 36.6+/-10.5% in Groups I, II and III, respectively (Group I vs. II and Group I vs. III ; p=0.52, p=0.01). Proteoglycans were abundant in Groups I and II, and alpha-actin was positive in the neointima cells. CONCLUSION: The role of cell proliferation and proteoglycans are important in the early period, but collagen plays a major role in the late period, following coronary stenting, in a porcine model.