Rutledge J C, Woo M M, Rezai A A, Curtiss L K, Goldberg I J
Department of Internal Medicine, School of Medicine, University of California, Davis 95616, USA.
Circ Res. 1997 Jun;80(6):819-28. doi: 10.1161/01.res.80.6.819.
Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and efflux were separately determined. Perfusion of arteries with buffer plus lipoprotein lipase (LpL) increased LDL accumulation 5-fold (0.1 +/- 0.03 mV/min [control] versus 0.5 +/- 0.05 mV/min [LpL]) by increasing LDL retention in the artery wall. This effect was blocked by heparin and monoclonal antibodies directed against the amino-terminal region of apolipoprotein B (apo B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effect of hydrolysis of triglyceride-rich lipoproteins on endothelial barrier function was studied. We compared endothelial layer permeability using a water-soluble reference molecule, fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma, dextran accumulation within the artery wall increased > 4-fold (0.024 +/- 0.01 mV/min [control] versus 0.098 +/- 0.05 mV/min [LpL]). Under the same conditions, LpL increased LDL accumulation approximately 3-fold (0.016 +/- 0.003 mV/min [control] versus 0.047 +/- 0.013 mV/min [LpL]). Rapid efflux of LDL from the artery wall indicated that increased endothelial layer permeability was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the amount of LDL in the artery wall. These findings may pertain to the observed relationship between increased postprandial lipemia and atherosclerosis.
在一种新的模型——灌注的仓鼠主动脉中，研究了负责低密度脂蛋白（LDL）积聚的机制。为此，我们开发了一种方法来实时研究单个灌注动脉中的LDL通量；每条动脉都作为自身的对照。使用定量荧光显微镜，分别测定了LDL的积聚和流出速率。用缓冲液加脂蛋白脂肪酶（LpL）灌注动脉，通过增加LDL在动脉壁中的潴留，使LDL积聚增加了5倍（对照为0.1±0.03 mV/分钟，LpL为0.5±0.05 mV/分钟）。这种作用被肝素和针对载脂蛋白B（apo B）氨基末端区域的单克隆抗体所阻断。这表明apo B的特定区域参与了动脉内LDL的积聚。此外，还研究了富含甘油三酯脂蛋白的水解对内皮屏障功能的影响。我们使用一种水溶性参考分子——荧光标记的葡聚糖，比较了内皮层的通透性。当将LpL添加到高甘油三酯血症血浆中时，动脉壁内葡聚糖的积聚增加了4倍以上（对照为0.024±0.01 mV/分钟，LpL为0.098±0.05 mV/分钟）。在相同条件下，LpL使LDL积聚增加了约3倍（对照为0.016±0.003 mV/分钟，LpL为0.047±0.013 mV/分钟）。LDL从动脉壁的快速流出表明，在内皮脂肪分解增加期间，内皮层通透性增加是主要机制。我们的数据证明了两种LpL介导的效应，它们可能会增加动脉壁中LDL的量。这些发现可能与餐后血脂升高与动脉粥样硬化之间观察到的关系有关。
