Olin-Lewis Katherine, Krauss Ronald M, La Belle Michael, Blanche Patricia J, Barrett P Hugh R, Wight Thomas N, Chait Alan
Department of Medicine, University of Washington, Seattle, WA, USA.
J Lipid Res. 2002 Nov;43(11):1969-77. doi: 10.1194/jlr.m200322-jlr200.
Retention of apolipoprotein (apo)B and apoE-containing lipoproteins by extracellular vascular proteoglycans is critical in atherogenesis. Moreover, high circulating apoC-III levels are associated with increased atherosclerosis risk. To test whether apoC-III content of apoB-containing lipoproteins affects their ability to bind to the vascular proteoglycan biglycan, we evaluated the impact of apoC-III on the interaction of [(35)S]SO(4)-biglycan derived from cultured arterial smooth muscle cells with lipoproteins obtained from individuals across a spectrum of lipid concentrations. The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r = 0.78, P < 0.01), IDL (r = 0.67, P < 0.01), and LDL (r = 0.52, P < 0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apoC-III-containing lipoprotein particles in plasma by anti-apoC-III immunoaffinity chromatography. Since apoC-III does not bind biglycan directly, enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apoB and/or apoE become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apoC-III enrichment of LDL and VLDL did not increase binding. ApoC-III content may thus be a marker for lipoproteins characterized as having an increased ability to bind proteoglycans.
细胞外血管蛋白聚糖对载脂蛋白（apo）B和含apoE脂蛋白的保留在动脉粥样硬化形成过程中至关重要。此外，循环中apoC-III水平升高与动脉粥样硬化风险增加相关。为了测试含apoB脂蛋白的apoC-III含量是否影响其与血管蛋白聚糖双糖链蛋白聚糖结合的能力，我们评估了apoC-III对来自培养的动脉平滑肌细胞的[（35）S]SO（4）-双糖链蛋白聚糖与从脂质浓度范围各异的个体获得的脂蛋白之间相互作用的影响。双糖链蛋白聚糖结合程度与极低密度脂蛋白（VLDL）（r = 0.78，P < 0.01）、中间密度脂蛋白（IDL）（r = 0.67，P < 0.01）和低密度脂蛋白（LDL）（r = 0.52，P < 0.05）中的apoC-III水平呈正相关。此外，通过抗apoC-III免疫亲和层析去除血浆中含apoC-III的脂蛋白颗粒后，VLDL、IDL和LDL与双糖链蛋白聚糖的结合减少。由于apoC-III不直接结合双糖链蛋白聚糖，增强的双糖链蛋白聚糖结合可能是由于与apoC-III含量增加相关的构象变化导致apoB和/或apoE更容易被蛋白聚糖识别。这可能是脂蛋白的固有特性，因为外源性apoC-III富集LDL和VLDL并未增加结合。因此，apoC-III含量可能是脂蛋白具有增加的与蛋白聚糖结合能力的一个标志物。
