Intestinal ABCA1 directly contributes to HDL biogenesis in vivo
Intestinal ABCA1 directly contributes to HDL biogenesis in vivo
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DOI：
10.1172/jci27352
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发表时间：
2006-04-01
影响因子：
15.9
通讯作者：
Hayden, MR
中科院分区：
文献类型：
--
作者：
Brunham, LR;Kruit, JK;Hayden, MR
血浆高密度脂蛋白胆固醇水平与动脉粥样硬化风险呈负相关。ATP结合盒，亚家族A，成员1（ABCA 1）介导HDL颗粒形成的速率控制步骤，游离胆固醇和磷脂与apoA-I的组装。ABCA 1在许多组织中表达;然而，ABCA 1在特定组织和器官中的生理功能仍然是难以捉摸的。已知肝脏是血浆HDL的主要来源，但可能还有其他重要的HDL生物合成位点。为了评估肠道ABCA 1对体内血浆HDL水平的贡献，我们产生了肠道中特异性缺乏ABCA 1的小鼠。我们的研究结果表明，大约30%的稳态血浆HDL池是由肠道ABCA 1在小鼠。此外，我们的数据表明，HDL来源于肠道ABCA 1直接分泌到循环中，淋巴中的HDL主要来源于血浆室。这些数据确立了肠道ABCA 1在体内血浆HDL生物合成中的关键作用。
Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. The liver is known to be the major source of plasma HDL, but it is likely that there are other important sites of HDL biogenesis. To assess the contribution of intestinal ABCA1 to plasma HDL levels in vivo, we generated mice that specifically lack ABCA1 in the intestine. Our results indicate that approximately 30% of the steady-state plasma HDL pool is contributed by intestinal ABCA1 in mice. In addition, our data suggest that HDL derived from intestinal ABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment. These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo.