Neointima formation after vascular stent implantation. Spatial and chronological distribution of smooth muscle cell proliferation and phenotypic modulation.

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Abstract
Intravascular stents have proved useful as angioplasty devices, but intimal hyperplasia after stent implantation remains an unsolved problem. In the present study, we analyzed the spatial and chronological distribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after stent implantation (Gianturco's Z type) by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (SM1, 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-positive and SM2-negative). They migrated into the intima and proliferated 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 implantati...

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