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正常和高胆固醇血症白卡诺鸽体内低密度脂蛋白和β-极低密度脂蛋白的清除情况

In vivo clearance of low-density lipoproteins and beta-very-low-density lipoproteins in normal and hypercholesterolemic White Carneau pigeons.

作者信息

Reagan J W, St Clair R W

机构信息

Department of Pathology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27103.

出版信息

Biochim Biophys Acta. 1991 Jan 28;1081(2):202-10. doi: 10.1016/0005-2760(91)90027-f.

DOI:10.1016/0005-2760(91)90027-f
PMID:1998739
Abstract

Low-density lipoproteins (hLDL) and beta-migrating-very-low-density lipoproteins (beta-VLDL) were isolated from the plasma of cholesterol-fed White Carneau (WC) pigeons and low-density lipoproteins (nLDL) were isolated from the plasma of grain-fed WC pigeons. The lipoproteins were radiolabeled with 125I or 131I and injected into normocholesterolemic or hypercholesterolemic WC pigeons to determine their rate of clearance from the plasma. The fractional catabolic rate (FCR) of nLDL and hLDL in normocholesterolemic pigeons averaged 0.202 and 0.206 pools/h.respectively. beta-VLDL was cleared at a significantly slower rate of 0.155 pools/h. The FCR of the same lipoproteins injected into hypercholesterolemic pigeons was reduced by 17% for nLDL, 50% for hLDL and 57% for beta-VLDL, indicating that the effect of hypercholesterolemia on clearance in vivo was different for the three lipoproteins. The FCR of reductively methylated pigeon LDL (MeLDL), which gives a measure of receptor-independent clearance of LDL, was shown previously to be 0.037 pools/h. These studies suggest therefore that LDL and beta-VLDL are cleared from the plasma of normocholesterolemic and hypercholesterolemic pigeons at a rate substantially greater than that predicted for non-specific processes. Despite the reduction in the clearance rate of hLDL and beta-VLDL due to cholesterol feeding, the absolute amount of cholesterol that was cleared from the plasma by these lipoproteins was increased from approx. 200 mg/kg body weight per day in the normocholesterolemic pigeons to greater than 1000 mg/kg body weight per day in the hypercholesterolemic pigeons. This is due principally to the enrichment in cholesterol relative to protein of the lipoproteins isolated from cholesterol-fed pigeons and the failure of hypercholesterolemia to completely inhibit receptor-dependent clearance of LDL and beta-VLDL. The lower rate of clearance of beta-VLDL relative to LDL is in marked contrast to mammalian beta-VLDL, which is cleared much faster than LDL, but is consistent with the lack of apo E on pigeon lipoproteins. Apo E is the apoprotein that is thought to be responsible for the rapid clearance of beta-VLDL in normocholesterolemic mammals. The low rate of beta-VLDL clearance in pigeons also suggests that pigeons lack an apolipoprotein that function like mammalian apo E.

摘要

从喂食胆固醇的白卡诺(WC)鸽血浆中分离出低密度脂蛋白(hLDL)和β-迁移极低密度脂蛋白(β-VLDL),从喂食谷物的WC鸽血浆中分离出低密度脂蛋白(nLDL)。这些脂蛋白用125I或131I进行放射性标记,然后注射到正常胆固醇血症或高胆固醇血症的WC鸽体内,以测定它们从血浆中的清除率。正常胆固醇血症鸽体内nLDL和hLDL的分解代谢率(FCR)平均分别为0.202池/小时和0.206池/小时。β-VLDL的清除速度明显较慢,为0.155池/小时。注射到高胆固醇血症鸽体内的相同脂蛋白的FCR,nLDL降低了17%,hLDL降低了50%,β-VLDL降低了57%,这表明高胆固醇血症对三种脂蛋白体内清除的影响不同。还原甲基化鸽低密度脂蛋白(MeLDL)的FCR(可衡量低密度脂蛋白的非受体依赖性清除)先前已证明为0.037池/小时。因此,这些研究表明,正常胆固醇血症和高胆固醇血症鸽血浆中LDL和β-VLDL的清除速度大大高于非特异性过程所预测的速度。尽管由于喂食胆固醇导致hLDL和β-VLDL的清除率降低,但这些脂蛋白从血浆中清除的胆固醇绝对量却从正常胆固醇血症鸽每天约200毫克/千克体重增加到高胆固醇血症鸽每天超过1000毫克/千克体重。这主要是由于从喂食胆固醇的鸽体内分离出的脂蛋白中胆固醇相对于蛋白质的富集,以及高胆固醇血症未能完全抑制LDL和β-VLDL的受体依赖性清除。与哺乳动物的β-VLDL相比,β-VLDL相对于LDL的清除率较低,哺乳动物的β-VLDL清除速度比LDL快得多,但这与鸽脂蛋白上缺乏载脂蛋白E是一致的。载脂蛋白E是一种载脂蛋白,被认为是正常胆固醇血症哺乳动物中β-VLDL快速清除的原因。鸽体内β-VLDL清除率低也表明鸽缺乏一种功能类似于哺乳动物载脂蛋白E的载脂蛋白。

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