Apolipoprotein J/clusterin is induced in vascular smooth muscle cells after vascular injury

Background-Understanding the precise molecular mechanisms underlying the ph enomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to i dentify the genes involved in vascular restenosis. Methods and Results-Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apoli poprotein J (apoJ)/clusterin, were constitutively expressed in noninjured a orta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, a nd returned to the control level at 24 weeks. Western blot and immunohistoc hemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55- fold increase) at 2 to 8 weeks. The expression of apoJ protein continued un til 24 weeks after injury. In situ hybridization revealed that apoJ mRNA wa s expressed in smooth muscle cells (SMCs) of media at 2 days after injury a nd in SMCs of media and neointima at 2 weeks. To analyze the function of ap oJ, stably transfected rabbit SMCs were created. The expression of apoJ sti mulated proliferation and migration of SMCs. Conclusions-ApoJ is dramatically induced in media and neointima after vascu lar injury, suggesting that apoJ contributes to restenosis after angioplast y.