Goulter Andrew B, Avella Michael, Botham Kathleen M, Elliott Jonathan
Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College St, London NW1 0TU, UK.
Clin Sci (Lond). 2003 Sep;105(3):363-71. doi: 10.1042/CS20030039.
The effects of chylomicron remnants on the activity of basally produced nitric oxide (NO) from porcine coronary artery rings and porcine aortic endothelial cells were studied by investigating the effects of chylomicron-remnant-like particles (CMR-LPs) containing porcine apolipoprotein E on the vessel tone of porcine coronary arteries and on cGMP release by aortic endothelial cells. CMR-LPs were oxidized by incubation with CuSO(4) (10 microM) for 18 h at 37 degrees C. N (omega)-nitro-L-arginine (L-NOARG) and oxidized CMR-LPs (oxCMR-LPs), but not native CMR-LPs, increased the vessel tone of static porcine coronary artery rings (increase in tone as a percentage of the tone induced by depolarizing Krebs-Henseleit solution: L-NOARG, 14.24 +/- 2.09; oxCMR-LPs, 4.98 +/- 0.88; and native CMR-LPs, 0.47 +/- 0.21). L-NOARG, endothelium removal and oxCMR-LPs also all significantly increased the maximum relaxation of the vessels to S -nitroso- N -acetyl-DL-penicillamine. In addition, oxCMR-LPs reduced the amounts of cGMP released by porcine aortic endothelial cells into the culture medium from 116 +/- 12.0 to 84.2 +/- 11.6 fmol/microg of cellular protein, mimicking the effects of L-NOARG. These results indicate that oxCMR-LPs, but not native CMR-LPs, inhibit the activity, production or release of NO from unstimulated porcine coronary and aortic endothelial cells. oxCMR-LPs mimicked the addition of L-NOARG and endothelium removal in these experimental systems, suggesting that the lipoproteins were interfering with the L-arginine/NO pathway. This study provides further evidence to support a role of chylomicron remnants in the development of atherosclerosis.
通过研究含有猪载脂蛋白E的乳糜微粒残粒样颗粒（CMR-LPs）对猪冠状动脉血管张力以及主动脉内皮细胞环磷酸鸟苷（cGMP）释放的影响，探讨了乳糜微粒残粒对猪冠状动脉环和猪主动脉内皮细胞基础产生的一氧化氮（NO）活性的作用。CMR-LPs在37℃下与10微摩尔硫酸铜（CuSO₄）孵育18小时进行氧化。N（ω）-硝基-L-精氨酸（L-NOARG）和氧化型CMR-LPs（oxCMR-LPs），而非天然CMR-LPs，增加了静态猪冠状动脉环的血管张力（张力增加百分比以去极化Krebs-Henseleit溶液诱导的张力为参照：L-NOARG为14.24±2.09；oxCMR-LPs为4.98±0.88；天然CMR-LPs为0.47±0.21）。L-NOARG、去除内皮和oxCMR-LPs也均显著增加了血管对S-亚硝基-N-乙酰-DL-青霉胺的最大舒张反应。此外，oxCMR-LPs使猪主动脉内皮细胞释放到培养基中的cGMP量从116±12.0降至84.2±11.6飞摩尔/微克细胞蛋白，模拟了L-NOARG的作用。这些结果表明，oxCMR-LPs而非天然CMR-LPs抑制了未受刺激的猪冠状动脉和主动脉内皮细胞中NO的活性、产生或释放。在这些实验系统中，oxCMR-LPs模拟了添加L-NOARG和去除内皮的作用，提示脂蛋白干扰了L-精氨酸/NO途径。本研究为支持乳糜微粒残粒在动脉粥样硬化发展中的作用提供了进一步证据。
