Abstract
BackgroundArterial remodelling is a major pathologic change of restenosis after percutaneous coronary intervention (PCI). Our previous studies showed that XS0601 (consisting of Chuangxingol and paeoniflorin) had some effects on the prevention of restenosis after PCI. Therefore, the purpose of this study was to examine whether and how its mechanism was related to the regulation of the arterial remodelling after endothelial injury by balloon dilation.MethodsTwenty Chinese mini-pigs were randomized into four groups: control, probucol, low-dose XS0601 and high-dose XS0601 group before oversized balloon injury of the left anterior descending coronary arteries. Starting from two days before balloon injury, the mini-pigs in the treated group were administered with probucol (2 g/day) and XS0601 (0.02 g/kg/day for low dose; 0.04 g/kg/day for high dose) for four weeks after balloon injury. The animals receiving balloon injury alone were used as control. Morphometric and angiographic analysis of the injured arteries were performed.ResultsThe contribution of intimal hyperplasia and arterial remodelling to angiographic late lumen loss was 41% and 59% respectively. XS0601 markedly inhibited proliferation of smooth muscle cells (SMCs) and transformation of SMCs from contractile to synthetic phenotype in neointima, inhibited hyperplasia-related indices of morphometric analysis and reduce late angiographic lumen loss. The reduction of the late angiographic lumen loss resulting from vascular remodelling was greater after XS0601 treatment.ConclusionBoth intimal hyperplasia and vascular remodelling are attributed to late lumen loss in this porcine coronary injury model. XS0601 markedly reduced angiographic late lumen loss resulting from intimal hyperplasia, vascular remodelling and XS0601 may be a potential agent to prevent restenosis after PCI.
Highlights
Arterial remodelling is a major pathologic change of restenosis after percutaneous coronary intervention (PCI)
General comparison of the characteristics including MIT, injury score, LA, IELa, EELa, MA, IA, residual lumen (RL) (%) and Proliferation index (PI) between treatment and control groups are listed in Tables 2 and 3
As intimal hyperplasia after balloon dilation varied in proportion to injury in this model [13,14], quantitative group comparison was performed and the vessel injury score was used as a covariance
Summary
Arterial remodelling is a major pathologic change of restenosis after percutaneous coronary intervention (PCI). Our previous studies showed that XS0601 (consisting of Chuangxingol and paeoniflorin) had some effects on the prevention of restenosis after PCI. The porcine model for studying restenosis has specific advantages over other animal models because of its similarities to the human coronary circulation, the spontaneous development of atherosclerosis and the response to vascular injury [9]. In a balloon injury model of coronary restenosis in normolipemic swine, intimal smooth muscle cell proliferation is histologically similar to the hyperplasia in human restenosis [10]. The purpose of the present study is to observe the effect of XS0601 on vascular remodelling in a porcine coronary injury model and to determine whether it will be a potential agent for preventing restenosis
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