Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL.
Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL.
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DOI：
10.1186/1475-2840-13-64
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发表时间：
2014-03-25
影响因子：
9.3
通讯作者：
Chen CH
中科院分区：
文献类型：
--
作者：
Lee AS;Chen WY;Chan HC;Hsu JF;Shen MY;Chang CM;Bair H;Su MJ;Chang KC;Chen CH
在代谢综合征（MetS）和st段抬高型心肌梗死患者的血浆中观察到电负性最强的低密度脂蛋白L5水平升高，并可诱导内皮功能障碍。由于男性比绝经前女性更容易患冠状动脉疾病，我们假设LDL电负性在男性中增加并促进内皮损伤。比较了中年男性和年龄匹配的绝经前女性（有或没有MetS）之间的L5水平。通过衰老相关的- β-半乳糖苷酶和γ - h2ax染色，我们进一步研究了性别影响的LDL电负性对瘦素受体缺陷（db/db）小鼠主动脉细胞衰老和DNA损伤的影响。我们还研究了17β-雌二醇和染料木素对培养的牛主动脉内皮细胞（BAECs）电负性ldl诱导的衰老的保护作用。met患者的L5水平高于健康受试者（P < 0.001），尤其是男性（P = 0.001）。从雄性db/db小鼠中分离的LDL比从雄性和雌性野生型小鼠中分离的LDL具有更强的电负性。此外，雄性db/db小鼠的LDL比雌性db/db或野生型LDL含有更多的载脂蛋白CIII，并诱导更多的BAEC衰老。在db/db小鼠而非野生型小鼠的主动脉中，我们观察到细胞衰老和DNA损伤，并且雄性db/db小鼠的作用比雌性db/db小鼠更显著。17β-雌二醇或染料木素预处理可抑制雄性或雌性db/db LDL诱导的BAEC衰老，下调凝集素样氧化LDL受体-1和肿瘤坏死因子- α蛋白的表达。低密度脂蛋白引起的心血管损伤的性别二分法可能是男性冠状动脉疾病倾向增加的基础。
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. 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). 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. The gender dichotomy of LDL-induced cardiovascular damage may underlie the increased propensity to coronary artery disease in men.
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影响因子：
3.7
作者：
Chu CS;Wang YC;Lu LS;Walton B;Yilmaz HR;Huang RY;Sawamura T;Dixon RA;Lai WT;Chen CH;Lu J
通讯作者：
Lu J
影响因子：
37.8
作者：
Chen, CH;Jiang, T;Yang, CY
通讯作者：
Yang, CY
影响因子：
20.3
作者：
Chan, Hua-Chen;Ke, Liang-Yin;Chen, Chu-Huang
通讯作者：
Chen, Chu-Huang
影响因子：
9.3
作者：
Kautzky-Willer, Alexandra;Stich, Kathrin;Lemmens-Gruber, Rosa
通讯作者：
Lemmens-Gruber, Rosa
影响因子：
20.1
作者：
Lu, Jonathan;Yang, Jun-Hai;Chen, Chu-Huang
通讯作者：
Chen, Chu-Huang