Apoptosis and Bcl-xs in the intimal thickening of balloon-injured carotid arteries

We performed balloon injury in the rat carotid artery and identified intima l thickening after injury. Balloon-injured carotid arteries showed maximum thickness of the neointima on the 14th day before complete endothelial cell regeneration. In this lesion we identified apoptosis of vascular smooth mu scle cells (VSMCs) by in situ DNA labelling and electron microscopy in the neointima on the 14th day after injury, mRNA expression levels of bcl-2, bo x, bcl-x, p53 and cospose-1 were determined by the reverse transcriptase-po lymerase chain reaction method both in injured and uninjured carotid arteri es. Neither bcl-2 nor bcl-xl mRNA expression was detected in either injured or uninjured arteries, whereas box and P53 mRNA expression was identified and their mRNA levels were not altered after balloon injury. In contrast, b oth bcl-xs and caspase-1 mRNA was detected and was markedly induced only in the injured carotid artery. Positive staining for immunoreactive Bcl-x was observed specifically in the injured arterial wall and co-localized with p ositive staining of nuclei identified by in situ DNA labelling. We conclude that two opposite cellular responses, VSMC proliferation and apoptosis, ex ist together in the neointima of the rat carotid artery after balloon injur y, and selective induction of Bcl-xs expression is a key regulator of VSMC apoptosis in the process of vascular remodelling.