Lipid Metabolism Laboratory, Tufts University, Boston, MA 02111, USA.
Metabolism. 2013 Mar;62(3):369-75. doi: 10.1016/j.metabol.2012.08.008. Epub 2012 Sep 25.
Inflammation plays an important role in atherosclerosis. Elevated C-reactive protein (CRP) levels are associated with a greater risk of cardiovascular disease. Our goal was to study CRP metabolism, and to determine its relationship with lipoprotein metabolism using stable isotope methodology.
MATERIAL/METHODS: Eight subjects with combined hyperlipidemia underwent a 15-h primed-constant infusion with deuterated leucine. CRP was purified from the plasma density fraction greater than 1.21g/ml by affinity chromatography. Lipoprotein fractions were separated by sequential ultracentrifugation. Isotope enrichment was determined by gas chromatography/mass spectrometry.
The subjects had mean LDL-C levels of 147.5mg/dl and mean CRP levels of 3.4mg/l. The mean CRP production rate (PR) was 0.050±0.012mg/kg/day and the mean CRP fractional catabolic rate (FCR) was 0.343±0.056 pools/day (residence time 2.92days). CRP pool size (PS) was significantly related to production (r=0.93; p<0.001), but not FCR. CRP PS was also related to body mass index (r=0.79; p=0.02). There was a significant association between CRP FCR and TRL apoB-100 FCR (r=0.74, p=0.04), as well as between CRP PS and TRL apoB-48 FCR (r=-0.90, p=0.002), indicating linkage between CRP and TRL metabolism.
The main determinant of plasma CRP levels was CRP production rate. Moreover a significant linkage between CRP metabolism and both TRL apoB-100 and apoB-48 catabolism was noted.
炎症在动脉粥样硬化中起着重要作用。C 反应蛋白(CRP)水平升高与心血管疾病风险增加相关。我们的目标是使用稳定同位素方法研究 CRP 代谢,并确定其与脂蛋白代谢的关系。
材料/方法:8 名合并高脂血症的患者接受了 15 小时的氘标记亮氨酸脉冲-恒速输注。通过亲和层析从血浆密度大于 1.21g/ml 的部分纯化 CRP。通过连续超速离心分离脂蛋白部分。通过气相色谱/质谱法测定同位素丰度。
患者的 LDL-C 平均水平为 147.5mg/dl,CRP 平均水平为 3.4mg/l。CRP 的平均生成率(PR)为 0.050±0.012mg/kg/天,CRP 的平均分解代谢率(FCR)为 0.343±0.056 池/天(停留时间 2.92 天)。CRP 库大小(PS)与生成率显著相关(r=0.93;p<0.001),但与 FCR 无关。CRP PS 也与体重指数(r=0.79;p=0.02)相关。CRP FCR 与 TRL apoB-100 FCR 之间存在显著相关性(r=0.74,p=0.04),CRP PS 与 TRL apoB-48 FCR 之间也存在显著相关性(r=-0.90,p=0.002),表明 CRP 与 TRL 代谢之间存在联系。
血浆 CRP 水平的主要决定因素是 CRP 生成率。此外,还观察到 CRP 代谢与 TRL apoB-100 和 apoB-48 分解代谢之间存在显著联系。