Lipid peroxidation triggers both c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK) activation and neointimal hyperplasia induced by cessation of blood flow in the mouse carotid artery

We investigated whether lipid peroxidation might influence activation of the mitogen activated protein kinase (MAPK) extracellular regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) in neointimal hyperplasia induced by flow interruption of carotid artery in mice. C57/BL6 mice were subjected to a complete ligation of the left common carotid artery or to a sham ligation. Animals were randomized to receive either IRFI-042, a Vitamin E-like inhibitor of lipid peroxidation (20 mg/kg/i.p., immediately after artery occlusion) or its vehicle (1 ml/kg of a NaCl-DMSO solution). The extent of lipid peroxidation (investigated by the means of conjugated dienes levels) and JNK and ERK activation were evaluated by Western blot analysis after blood flow interruption. ICAM-1 expression in injured arteries was investigated 4 days after artery ligation by the means of reverse transcriplase polymerase chain reaction (RT-PCR) and quantification of the ICAM-1 protein levels. Morphometric analysis of the structural alteration caused by the disruption of the arterial blood flow was performed 4 weeks after surgery.