Effects of human C-reactive protein on pathogenesis of features of the metabolic syndrome.
Effects of human C-reactive protein on pathogenesis of features of the metabolic syndrome.
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DOI：
10.1161/hypertensionaha.110.164350
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发表时间：
2011-04
期刊：
影响因子：
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通讯作者：
Kurtz TW
中科院分区：
文献类型：
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作者：
Pravenec M;Kajiya T;Zídek V;Landa V;Mlejnek P;Simáková M;Silhavý J;Malínská H;Oliyarnyk O;Kazdová L;Fan J;Wang J;Kurtz TW
关于C-反应蛋白（CRP）的增加是否有助于代谢综合征的各个组成部分，或者只是炎症性疾病过程的继发反应，存在重大争议。我们测量了自发性高血压大鼠（SHR）的血压和代谢表型，其中我们在apoE启动子的控制下在肝脏中转基因表达人CRP。在SHR转基因大鼠中，人CRP的血清水平接近大鼠中正常发现的CRP的内源性水平。通过遥测测量，表达人CRP的转基因SHR的收缩压和舒张压比SHR对照组高10-15 mmHg（P<0.01）。在口服葡萄糖耐量试验中，转基因SHR与对照组相比表现出高胰岛素血症（胰岛素曲线下面积分别为36±7和8±2 nmol/L/2 h，P<0.05）。转基因SHR对胰岛素刺激的骨骼肌糖原生成也表现出抵抗（174±18 vs 278±32 nmol葡萄糖/g/2 h，P<0.05），高甘油三酯血症（0.84± 0.05vs 0.64± 0.03mmol/L，P<0.05），降低血清脂联素水平（2.4±0.3 vs 4.3±0.6 mmol/L，P<0.05），微量白蛋白尿（分别为200±35 vs 26±5 mg白蛋白/g肌酐，P<0.001）。转基因SHR有炎症和氧化性组织损伤的证据，血清白细胞介素6（IL 6）水平升高（36.4±5.2 vs 18±1.7 pg/ml，P<0.005），肝和肾TBARS增加（分别为1.2±0.09对0.8±0.07和1.5±0.1对1.1±0.05 nM/mg蛋白，P<0.01），表明氧化应激可能介导人CRP升高的不良反应。这些发现与CRP升高不仅仅是炎症标志物的假设一致，并且可以直接促进代谢综合征的多种特征。
Major controversy exists as to whether increased C-reactive protein (CRP) contributes to individual components of the metabolic syndrome or is just a secondary response to inflammatory disease processes. We measured blood pressure and metabolic phenotypes in spontaneously hypertensive rats (SHR) in which we transgenically expressed human CRP in liver under control of the apoE promoter. In SHR transgenic rats, serum levels of human CRP approximated the endogenous levels of CRP normally found in the rat. Systolic and diastolic blood pressures measured by telemetry were 10–15 mmHg greater in transgenic SHR expressing human CRP than in SHR controls (P<0.01). During oral glucose tolerance testing, transgenic SHR exhibited hyperinsulinemia compared to controls (insulin area under the curve 36±7 versus 8±2 nmol/L/2h, respectively, P<0.05). Transgenic SHR also exhibited resistance to insulin stimulated glycogenesis in skeletal muscle (174±18 versus 278±32 nmol glucose/g/2h, P<0.05), hypertriglyceridemia (0.84±0.05 versus 0.64±0.03 mmol/L, P<0.05), reduced serum adiponectin (2.4±0.3 versus 4.3±0.6 mmol/L, P<0.05), and microalbuminuria (200±35 versus 26±5 mg albumin/g creatinine, respectively, P<0.001). Transgenic SHR had evidence of inflammation and oxidative tissue damage with increased serum levels of interleukin 6 (IL6) (36.4±5.2 versus 18±1.7 pg/ml, P<0.005) and increased hepatic and renal TBARS (1.2±0.09 versus 0.8±0.07 and 1.5±0.1 versus 1.1±0.05 nM/mg protein, respectively, P<0.01), suggesting that oxidative stress may be mediating adverse effects of increased human CRP. These findings are consistent with the hypothesis that increased CRP is more than just a marker of inflammation and can directly promote multiple features of the metabolic syndrome.