Lee A.-S.Chen W.-Y.Chan H.-C.Hsu J.-F.Shen M.-Y.Chang C.-M.Bair H.MING-JAI SUChang K.-C.Chen C.-H.2021-05-312021-05-31201414752840https://scholars.lib.ntu.edu.tw/handle/123456789/563946Background: Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage.Methods: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS. We further studied the effects of gender-influenced LDL electronegativity on aortic cellular senescence and DNA damage in leptin receptor-deficient (db/db) mice by using senescence-associated-β-galactosidase and γH2AX staining, respectively. We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL-induced senescence in cultured bovine aortic endothelial cells (BAECs).Results: L5 levels were higher in MetS patients than in healthy subjects (P < 0.001), particularly in men (P = 0.001). LDL isolated from male db/db mice was more electronegative than that from male or female wild-type mice. In addition, LDL from male db/db mice contained abundantly more apolipoprotein CIII and induced more BAEC senescence than did female db/db or wild-type LDL. In the aortas of db/db mice but not wild-type mice, we observed cellular senescence and DNA damage, and the effect was more significant in male than in female db/db mice. Pretreatment with 17β-estradiol or genistein inhibited BAEC senescence induced by male or female db/db LDL and downregulated the expression of lectin-like oxidized LDL receptor-1 and tumor necrosis factor-alpha protein.Conclusion: The gender dichotomy of LDL-induced cardiovascular damage may underlie the increased propensity to coronary artery disease in men. ? 2014 Lee et al.; licensee BioMed Central Ltd.[SDGs]SDG3estradiol; genistein; low density lipoprotein; oxidized low density lipoprotein receptor 1; tumor necrosis factor alpha; adult; animal experiment; animal model; article; cardiovascular disease; clinical article; controlled study; coronary artery disease; disease predisposition; DNA damage; down regulation; endothelial dysfunction; endothelium cell; enzyme activity; fast protein liquid chromatography; female; heart protection; human; male; metabolic syndrome X; mouse; nonhuman; protein expression; senescence; sex difference; ST segment elevation myocardial infarction; waist circumference; Western blotting; wild type; Animals; Aorta; Cardiovascular Diseases; Cattle; Cells, Cultured; DNA Damage; Estrogens; Female; Humans; Lipoproteins, LDL; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Organ Culture Techniques; Sex Characteristicsjournal article10.1186/1475-2840-13-64246665252-s2.0-84897433208