MDPI, Journal of Clinical Medicine, 8(8), p. 1193, 2019
DOI: 10.3390/jcm8081193
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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.