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Abstract：
The most electronegative constituents of human plasma LDL (i.e., L5) and VLDL (i.e., V5) are highly atherogenic. We determined whether the combined electronegativity of L5 and V5 (i.e., L5 + V5) plays a role in coronary heart disease (CHD). In 33 asymptomatic individuals (ages 32-64), 10-year hard CHD risk correlated with age (r = 0.42, p = 0.01). However, in age-adjusted analyses, 10-year hard CHD risk correlated with L5 + V5 plasma concentration (r = 0.43, p = 0.01) but not age (p = 0.74). L5 + V5 plasma concentration was significantly greater in the group with high CHD risk (39.4 ± 22.0 mg/dL; n = 17) than in the group with low CHD risk (16.9 ± 14.8 mg/dL; n = 16; p = 0.01). In cultured human aortic endothelial cells, L5 + V5 treatment induced significantly more senescence-associated-β-Gal activity than did equal concentrations of L1 + V1 (n = 4, p < 0.001). To evaluate the in vivo relevance of these findings, we fed ApoE-/- and wild-type mice with a high-fat diet and found that plasma LDL, VLDL, and LDL + VLDL from ApoE-/- mice exhibited significantly greater electrophoretic mobility than did wild-type counterparts (n = 6, p < 0.01). The increased electronegativity of LDL and VLDL in ApoE-/- mice was accompanied by increased aortic lipid accumulation and cellular senescence (n = 6, p < 0.05). Clinical trials are warranted to test the predictive value of L5 + V5 concentration in patients with CHD.
摘要：
人血浆LDL的电负性最强的成分(即，L5)和VLDL(即V5)是高度致动脉粥样硬化的。我们确定L5和V5的组合电负性(即，L5+V5)在冠心病(CHD)中发挥作用。在33名无症状个体（32-64岁）中，10年硬冠心病风险与年龄相关(r=0.42,p=0.01)。然而,在年龄调整分析中，10年硬CHD风险与L5+V5血浆浓度相关（r=0.43，p=0.01），但与年龄无关（p=0.74）。冠心病高危人群的L5+V5血浆浓度(39.4±22.0mg/dL;n=17)明显高于冠心病高危人群(16.9±14.8mg/dL;n=16;p=0.01)。在培养的人主动脉内皮细胞中，L5+V5处理诱导的衰老相关β-Gal活性显著高于相同浓度的L1+V1(n=4,p<0.001)。为了评估这些发现的体内相关性，我们用高脂肪饮食喂养ApoE-/-和野生型小鼠，发现血浆LDL，VLDL,和来自ApoE-/-小鼠的LDL+VLDL表现出比野生型对应物显著更大的电泳迁移率(n=6,p<0.01)。ApoE-/-小鼠中LDL和VLDL的电负性增加伴随着主动脉脂质积累和细胞衰老的增加（n=6，p<0.05）。有必要进行临床试验以测试L5+V5浓度在CHD患者中的预测价值。
