role of heparanase on hepatic uptake of intestinal derived lipoprotein and fatty streak formation in mice角色的heparanase肝吸收形成小鼠肠道中脂蛋白和脂质条纹.pdfVIP

Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice 1 1 2 3 2 David Planer , Shulamit Metzger , Eyal Zcharia , Isaiah D. Wexler , Israel Vlodavsky , Tova Chajek-Shaul1* 1 Department of Medicine, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel, 2 Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel, 3 Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel Abstract Background: Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. Principal Findings: To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa- Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over- expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (