Department of Medicine, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.
PLoS One. 2011 Apr 4;6(4):e18370. doi: 10.1371/journal.pone.0018370.
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.
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 (23,984 µm(2)±5,922 vs. 4,189 µm(2)±1,130, p<0.001).
Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks.
肝素酶调节硫酸乙酰肝素蛋白聚糖（HSPGs）的水平，HSPGs 在多种细胞过程中具有重要作用。最近的研究表明，HSPGs 在肝脏脂蛋白处理和涉及脂蛋白颗粒清除的过程中具有重要功能。
为了确定 HSPGs 链长降低对脂蛋白代谢和动脉粥样硬化的影响，研究了过度表达人肝素酶基因的转基因小鼠。通过给予转基因小鼠口服脂肪负荷和标记视黄醇，评估 hpa-Tg 小鼠的肝脂质摄取。用动脉粥样硬化饮食喂养过度表达肝素酶（hpa-Tg）和对照（C57/BL6）的小鼠的主动脉切片检查动脉粥样硬化的证据。肝素酶过表达导致餐后脂蛋白在肝脏中的清除减少，空腹和餐后血清甘油三酯水平升高。肝素酶过表达还诱导主动脉中形成脂肪条纹。与对照小鼠相比，肝素酶过表达小鼠的平均病变截面积几乎高 6 倍（23984µm²±5922 与 4189µm²±1130，p<0.001）。
肝素酶的过表达证明了 HSPGs 对肠道衍生脂蛋白摄取的重要性及其在形成脂肪条纹中的作用。
