Prolonged proliferative response of smooth muscle cells after experimental intravascular stenting

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Abstract
The purpose of this experimental in vivo study was to determine the time course of smooth muscle cell proliferation early and late after intravascular stenting compared to conventional balloon angioplasty in normal vessels. A balloon expandable 2·0 mm tantalum Strecker stent was placed in the right carotid artery of 33 male New Zealand White rabbits after they had been fed a 0·5% cholesterol diet for 28 days. In addition, balloon angioplasty was performed in 27 of the animals; 19 contralateral vessels served as controls without treatment. The vessels were excised at 7, 14, 28, 42 or 90 days after treatment. During the final 18 h before the rabbits were killed, bromodeoxyuridine (BrdU) was applied and proliferating cells were detected by using a monoclonal antibody against BrdU. In histological cross sections the proportion of cells undergoing DNA synthesis was determined. Analysis was performed separately in the intimal and medial layers. Additionally, the area adjacent to the stent wire was compared with the intermediate area. Smooth muscle cells were identified by alpha-actin staining. Intimal wall thickness increased from 23 ± 28,μm (control group without intervention) to 323 ± 84μm within 42 days after slenting (P<0·01), and to 81 ± 82μm at day 42 after balloon angioplasty (P<005). However, between 42 and 90 days following stent implantation a significant (P<0·05) decrease in neointimal thickness was observed (90 days: 215 ± 15 μm). A significant increase in intimal cells undergoing DNA synthesis was found at day 7 (16·2 ±3·7%, P<0·001), day 14 (7·5 ± 1·2%, P<0·001), day 28 (4·1 ± 1·8%, P<0·001) and day 42 (2 ± 0·3%, P<0·01) after stenting as compared to the control group (0·3 ± 0·4%). Regional determination of proliferating cells in the area of the stent showed a significantly increased prolifération of smooth muscle cells (1·5 ± 0·5%, P<0·01) even 90 days after stent implantation. In contrast, after balloon treatment the proliferative activity was significantly increased at day 7 (13·4 ± 5·0%, P<0·0001), day 14 (2·2 ± 1·7%, P<0·0001) and day 28 (1·0 ± 0·4%, P<0·01) only. Compared to conventional balloon angioplasty, the proliferative response after intravascular stenting is increased and prolonged. Despite a decrease of intimal wall thickness between 42 and 90 days following stent implantation, the cellular proliferation in the area adjacent to the stent was still increased at 3 months after stenling.

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