Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice

摘要: Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures its induction results the attenuation monocyte chemotaxis resulting from treatment vitro. To elucidate role development atherosclerotic lesions vivo, we modulated expression LDL-receptor knockout mice fed high-fat diets. During 6-week diet trials, intraperitoneal injections hemin (H group) or desferrioxamine (HD to induce HO-1, Sn-protoporphyrin IX inhibit (Sn group), saline as control (C were performed. Both H HD groups showed significantly less mean proximal aorta compared C group, whereas Sn group larger lesion group. Modulation HO activities confirmed Northern blot analysis activity assay. Immunohistochemical studies revealed significant lesions, where phospholipids also localized. Major types expressing macrophages foam cells lesions. modulations affected plasma lipid hydroperoxide (LPO) levels nitrite/nitrate levels. These suggest under hyperlipidemia, functioned an intrinsic protective factor against formation, possibly inhibiting peroxidation influencing nitric oxide pathway.