Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits.
Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits.
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心脏瓣膜中的大分子运输。
DOI：
10.1152/ajpheart.00606.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Rumschitzki,DavidS
中科院分区：
文献类型：
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作者：
Zeng,Zhongqing;Nievelstein-Post,Patricia;Yin,Yongyi;Jan,Kung-Ming;Frank,JoyS;Rumschitzki,DavidS
在不进行常规化学固定/处理的情况下，通过超速冷冻检查29天胆固醇喂养的兔的心脏瓣膜小叶，然后进行旋转阴影冷冻蚀刻。这个过程中的图像小叶的内皮下细胞外基质非常详细，和细胞外脂质脂质体，从23至220纳米的直径，清楚地出现在那里。这些脂质体与基质丝连接并以簇的形式出现。它们的粒径分布显示60.7%的直径为23-69 nm，31.7%的直径在70 - 119 nm之间，7.3%的直径在120 - 169 nm之间，0.3%的直径在170 - 220 nm之间（超大型），这表明较小的脂质体可以融合成较大的脂质体。我们将本系列第二部分（Zeng Z，Yin Y，Jan KM，Rumschitzki DS.Am J Physiol Heart Circ Physiol 292：H2671-H2686，2007）中用于脂质转运至瓣叶的模型与最初针对主动脉脂质体提出的用于脂质体形成的成核-聚合模型层级结合，以预测心脏瓣膜中的脂质体形成/生长。模拟表明，最简单的这种模型不能解释所观察到的尺寸分布。然而，通过使用主动脉脂质体确定的参数包括脂质体融合/合并来修改该模型，导致预测的尺寸分布与我们的瓣膜数据非常一致。脂质体尺寸分布和总脂质体质量的演变表明，只有在高管腔胆固醇2周后，融合才变得显著。包括巨噬细胞的吞噬作用限制了否则单调增加的总脂质体质量，同时保持脂质体尺寸分布与数据的极好拟合。
The heart valve leaflets of 29-day cholesterol-fed rabbits were examined by ultrarapid freezing without conventional chemical fixation/processing, followed by rotary shadow freeze-etching. This procedure images the leaflets' subendothelial extracellular matrix in extraordinary detail, and extracellular lipid liposomes, from 23 to 220 nm in diameter, clearly appear there. These liposomes are linked to matrix filaments and appear in clusters. Their size distribution shows 60.7% with diameters 23–69 nm, 31.7% between 70 and 119 nm, 7.3% between 120 and 169 nm, and 0.3% between 170 and 220 nm (superlarge) and suggests that smaller liposomes can fuse into larger ones. We couple our model from Part II of this series (Zeng Z, Yin Y, Jan KM, Rumschitzki DS.Am J Physiol Heart Circ Physiol292: H2671–H2686, 2007) for lipid transport into the leaflet to the nucleation-polymerization model hierarchy for liposome formation proposed originally for aortic liposomes to predict liposome formation/growth in heart valves. Simulations show that the simplest such model cannot account for the observed size distribution. However, modifying this model by including liposome fusing/merging, using parameters determined from aortic liposomes, leads to predicted size distributions in excellent agreement with our valve data. Evolutions of both the liposome size distribution and total liposome mass suggest that fusing becomes significant only after 2 wk of high lumen cholesterol. Inclusion of phagocytosis by macrophages limits the otherwise monotonically increasing total liposome mass, while keeping the excellent fit of the liposome size distribution to the data.