In vitro effect of cholesterol on calcifying activity of vesicles isolated from rabbit aortas.
In vitro effect of cholesterol on calcifying activity of vesicles isolated from rabbit aortas.
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胆固醇对兔主动脉分离囊泡钙化活性的体外影响。
DOI：
10.1016/s0925-4439(03)00088-7
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Hsu,HowardHT
中科院分区：
文献类型：
--
作者：
Hsu,HowardHT
研究表明，囊泡在与胆固醇诱导的动脉粥样硬化相关的主动脉钙化的发病机制中起着关键作用。这项研究使用兔模型来确定胆固醇是否对囊泡的钙化能力产生直接影响。钙化介质中的胆固醇以剂量依赖的方式刺激ATP启动的钙沉积，这种方式是通过使用粗胶原酶消化从正常主动脉分离的小泡来实现的。相比之下，如果从动脉粥样硬化的动脉中分离出小泡，胆固醇对ATP促进的钙化没有显著影响。为了确定动脉粥样硬化囊泡制剂中的高胆固醇水平是否已经使钙化活性最大化，从而解释了囊泡对类固醇缺乏反应的原因，我们使用傅立叶变换红外光谱(FT-IR)来比较对照和动脉粥样硬化囊泡中的胆固醇含量。光谱图谱显示动脉粥样硬化性大动脉的囊泡制剂中的胆固醇水平高于正常大动脉。通过相对较低的离心力从动脉粥样硬化的囊泡中去除囊泡外的胆固醇胶束，使小泡对胆固醇刺激敏感，导致钙化活性增加2倍。在测试的各种氧化形式的胆固醇中，7-酮和6-酮胆固醇将活性提高了2倍。总之，这些观察表明，胆固醇，特别是其氧化形式，可能通过直接增强小泡的钙化能力而诱导主动脉钙化。
It has been shown that vesicles play a key role in the onset mechanism of aortic calcification related to cholesterol-induced atherosclerosis. This study using a rabbit model was conducted to determine whether cholesterol exerts a direct effect on vesicle's calcifiability. Inclusion of cholesterol in calcifying media stimulated ATP-initiated deposition of calcium in a dose-dependent manner by vesicles isolated from normal aortas using crude collagenase digestion. By contrast, cholesterol did not significantly affect ATP-promoted calcification if vesicles were isolated from atherosclerotic aortas. To determine whether high cholesterol levels in atherosclerotic vesicle preparations may have already maximized calcifying activity and therefore account for lack of the vesicle's response to the sterol, Fourier transform infrared spectroscopy (FT-IR) was used to compare the cholesterol contents in control and atherosclerotic vesicles. The spectral patterns revealed higher levels of cholesterol in vesicle preparations from atherosclerotic aortas than those from normal aortas. Removal of extra-vesicular cholesterol micelles from atherosclerotic vesicles by a relatively low centrifugal force sensitized the vesicles to cholesterol stimulation causing a 2-fold increase in calcifying activity. Of various oxidized forms of cholesterol tested, 7-keto and 6-keto cholesterol enhanced the activity by 2-fold. Altogether, these observations suggest that cholesterol and especially its oxidized forms may induce aortic calcification by directly enhancing the vesicle's ability to calcify.