PGHS-2 Derived Prostanoid Promote Vascular Smooth Muscle Cell Proliferation Response To Injury

Background and objective:Prostaglandin H synthase (PGHS), also known as Cyclooxygenase (COX), is the key enzyme in the biosynthesis of prostanoid and it plays an important role in the development of vascular inflammation such as atherosclerosis and post-angioplasty restenosis. Although selective inhibition of COX-2 increases the risk of heart attack and stock, little is known about its effect in vascular remodeling after interventional therapy. To investigate whether COX-2 derived prostanoid mediate vascular smooth muscle cell (VSMC) proliferation, femoral arterial intima were evaluated followed by wire-induced artery injury from both COX-2 knock out (KO) and COX-1>COX-2 mice, where the COX-1 gene was knocked-into COX-2 locus.Methods and Results:In this study, whether the mouse femoral artery injury model was established successfully was determined by immunofluorescence and HE staining. HE staining, Envision immunohistochemical method and image pro plus software were used to analyze the mice membrane and the membrane area ratio (I/M ratio). Femoral arterial remodeling was characterized 4 weeks after injury in COX-2 KO mice, COX-1>COX-2 mice and wild type (WT) controls. The immunohistochemical staining of VSMC marker (a-actin) showed that the neointima of injured vessels was almost completely composed of VSMCs in all the injured mice. The infiltration of macrophages and neutrophilic granulocytes in arterial lesion from COX-2 KO mice was significantly less than from COX-1>COX-2 mice (P<0.05) and WT controls (P<0.01). The intima/media ratio of injured artery was significantly reduced in the COX-2 KO mice (2.042±0.218) compared to COX-1>COX-2 mice (4.534±1.274, P<0.05) and WT controls (4.534±1.274, P<0.05). The results above indicate COX-2 deletion protects against VSMC proliferation response to injury. Conclusions:COX-2 derived prostanoid is involved in injury-induced arterial remodeling. These findings indicate that blockage of COX-2 downstream signaling may offer an approach to prevent arterial restenosis after angioplasty.