NEOINTIMA FORMATION AFTER VASCULAR STENT IMPLANTATION - SPATIAL AND CHRONOLOGICAL DISTRIBUTION OF SMOOTH-MUSCLE CELL-PROLIFERATION AND PHENOTYPIC MODULATION

Intravascular stents have proved useful as angioplasty devices, but in timal hyperplasia after stent implantation remains an unsolved problem . In the present study, we analyzed the spatial and chronological dist ribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after sten t implantation (Gianturco's Z type) by immunohistochemistry for prolif erating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (S M1, SM2, and SMemb). Stent implantation induced regional injury in the arterial wall. Medial SMCs then began to proliferate adjacent to the injured SMCs, maximally on day 4 (PCNA index in the media: 3.9+/-3.4% [mean+/-SD]), and were modulated to the embryonic phenotype (SMemb-pos itive and SM2-negative). They migrated into the intima and proliferate d most frequently on day 7 (PCNA index in the intima: 20.3+/-5.5%) and subsequently led to fibrocellular neointima formation at 2 weeks and later. At 1 month after implantation and later, SMC proliferation was rare, and the phenotype of intimal SMCs was gradually returning to the adult type (SMemb-negative and SM2-positive). Thus, this stent implan tation model demonstates that the regional effect on arterial wall by stenting leads to neointima formation through transient and regional p roliferation and migration of SMCs and their phenotypic modulations.