Hime Neil J, Drew Kate J, Wee Kevin, Barter Philip J, Rye Kerry-Anne
Lipid Research Group, The Heart Research Institute, Camperdown, Sydney, New South Wales 2050, Australia.
J Lipid Res. 2006 Jan;47(1):115-22. doi: 10.1194/jlr.M500284-JLR200. Epub 2005 Oct 12.
Human plasma HDLs are classified on the basis of apolipoprotein composition into those that contain apolipoprotein A-I (apoA-I) without apoA-II [(A-I)HDL] and those containing apoA-I and apoA-II [(A-I/A-II)HDL]. ApoA-I enters the plasma as a component of discoidal particles, which are remodeled into spherical (A-I)HDL by LCAT. ApoA-II is secreted into the plasma either in the lipid-free form or as a component of discoidal high density lipoproteins containing apoA-II without apoA-I [(A-II)HDL]. As discoidal (A-II)HDL are poor substrates for LCAT, they are not converted into spherical (A-II)HDL. This study investigates the fate of apoA-II when it enters the plasma. Lipid-free apoA-II and apoA-II-containing discoidal reconstituted HDL [(A-II)rHDL] were injected intravenously into New Zealand White rabbits, a species that is deficient in apoA-II. In both cases, the apoA-II was rapidly and quantitatively incorporated into spherical (A-I)HDL to form spherical (A-I/A-II)HDL. These particles were comparable in size and composition to the (A-I/A-II)HDL in human plasma. Injection of lipid-free apoA-II and discoidal (A-II)rHDL was also accompanied by triglyceride enrichment of the endogenous (A-I)HDL and VLDL as well as the newly formed (A-I/A-II)HDL. We conclude that, irrespective of the form in which apoA-II enters the plasma, it is rapidly incorporated into spherical HDLs that also contain apoA-I to form (A-I/A-II)HDL.
人血浆高密度脂蛋白(HDL)根据载脂蛋白组成可分为含有载脂蛋白A-I(apoA-I)而不含载脂蛋白A-II的(A-I)HDL和含有apoA-I和apoA-II的(A-I/A-II)HDL。ApoA-I作为盘状颗粒的一种成分进入血浆,这些颗粒被卵磷脂胆固醇酰基转移酶(LCAT)重塑为球形(A-I)HDL。ApoA-II以无脂形式或作为不含apoA-I的含apoA-II的盘状高密度脂蛋白((A-II)HDL)的一种成分分泌到血浆中。由于盘状(A-II)HDL是LCAT的不良底物,它们不会转化为球形(A-II)HDL。本研究调查了apoA-II进入血浆后的命运。将无脂apoA-II和含apoA-II的盘状重组HDL((A-II)rHDL)静脉注射到新西兰白兔体内,该物种缺乏apoA-II。在这两种情况下,apoA-II都迅速且定量地掺入球形(A-I)HDL中,形成球形(A-I/A-II)HDL。这些颗粒在大小和组成上与人类血浆中的(A-I/A-II)HDL相当。注射无脂apoA-II和盘状(A-II)rHDL还伴随着内源性(A-I)HDL和极低密度脂蛋白(VLDL)以及新形成的(A-I/A-II)HDL的甘油三酯富集。我们得出结论,无论apoA-II以何种形式进入血浆,它都会迅速掺入也含有apoA-I的球形HDL中,形成(A-I/A-II)HDL。