Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency
Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency
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DOI：
10.1038/89977
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发表时间：
2001-07-01
期刊：
影响因子：
82.9
通讯作者：
Tall, AR
中科院分区：
文献类型：
--
作者：
Jiang, XC;Qin, SC;Tall, AR
含ApoB脂蛋白（BLp）的分泌和水平增加通常发生在家族性高脂血症、肥胖症和糖尿病中。已知血浆磷脂转移蛋白（PLTP）在血管内代谢过程中介导BLp和HDL之间的磷脂转移。为了解决PLTP在血脂异常和动脉粥样硬化形成中可能发挥的作用，我们使用不同的高脂血症小鼠品系培育了编码PLTP基因缺陷的小鼠（PLTP缺陷小鼠）。在ApoB转基因和ApoE缺陷的背景下，PLTP缺陷导致BLp的产生和水平降低，并显着降低动脉粥样硬化。在ApoB转基因PLTP缺陷小鼠的肝细胞中，BLp分泌减少，当PLTP重新引入腺病毒中时，这种缺陷得到纠正。这些研究揭示了PLTP在调节BLp分泌中的主要的、意想不到的作用，并将PLTP鉴定为治疗靶点。
Increased secretion and levels of ApoB-containing lipoproteins (BLp) commonly occur in familiar hyperlipidemia, obesity and diabetes. The plasma phospholipid-transfer protein (PLTP) is known to mediate transfer of phospholipids between BLp and HDL during their intravascular metabolism. To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains. In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis. BLp secretion was diminished in hepatocytes from ApoB-transgenic PLTP-deficient mice, a defect that was corrected when PLTP was reintroduced in adenovirus. The studies reveal a major, unexpected role of PLTP in regulating the secretion of BLp and identify PLTP as a therapeutic target.