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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Analysis of Variance, Angioplasty, Balloon, Coronary, Animals, Arachidonate 12-Lipoxygenase, Carotid Artery Diseases, Cell Movement, Contrast Media, Disease Models, Animal, Fibronectins, Fluorescein, Hyperplasia, Leukocytes, Lipoxygenase Inhibitors, Male, RNA, Catalytic, RNA, Messenger, Rats, Rats, Sprague-Dawley, Transfection, Tunica Intima.
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Does ribozyme-mediated inhibition of rat leukocyte-type 12-lipoxygenase prevent intimal hyperplasia in balloon-injured rat carotid arteries? Context: 12-Lipoxygenase (12-LO) products of arachidonate metabolism have growth and chemotactic effects in vascular smooth muscle cells. We have also recently demonstrated increased 12-LO mRNA and protein expression in the neointima of balloon-injured rat carotid arteries. In this study, we evaluated whether 12-LO activation plays a role in neointimal thickening in this rat model by using a specific ribozyme (Rz) directed to rat 12-LO. We designed a chimeric DNA-RNA hammerhead Rz to cleave rat leukocyte-type 12-LO mRNA. This Rz dose-dependently cleaved a 166-nucleotide target 12-LO mRNA substrate in vitro and reduced 12-LO mRNA and protein expression in rat vascular smooth muscle cells. A control mutant Rz (MRz) with a point mutation in the catalytic site was inactive. To test the in vivo efficacy of the 12-LO Rz, the left common carotid arteries of rats were injured with a balloon catheter. The distal half of the injured arteries was treated with Rz or MRz mixed with lipofectin. The proximal half received only lipofectin. Twelve days after injury, intima-to-media ratios were significantly lower in the Rz-treated sections than in untreated sections from the same rat (0.742+/-0.16 versus 1.749+/-0.12, P:<0.001). In contrast, the MRz had no significant effect.
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These results indicate the important role of the leukocyte-type 12-LO pathway in restenosis in response to injury. Final Decision: yes