Keller Amy C, Klawitter Jelena, Hildreth Kerry L, Christians Uwe, Putnam Kelly, Kohrt Wendy M, Reusch Jane E B, Moreau Kerrie L
Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, Colorado.
Denver Veterans Affairs Medical Center , Denver, Colorado.
J Appl Physiol (1985). 2019 Jun 1;126(6):1533-1540. doi: 10.1152/japplphysiol.00819.2018. Epub 2019 Mar 21.
Hyperhomocysteinemia is associated with endothelial dysfunction and increased cardiovascular disease (CVD). We determined whether elevated homocysteine (Hcy) and markers of Hcy metabolism were associated with the previously reported endothelial dysfunction across stages of the menopause transition. Brachial artery flow-mediated dilation (FMD) and plasma concentrations of Hcy, cysteine, and methionine were measured in healthy women ( = 128) 22-70 yr of age categorized as premenopausal ( = 35), perimenopausal (early: = 16; late: = 21), and postmenopausal (early: = 21; late: = 35). Dietary intake of micronutrients involved in Hcy metabolism (e.g., vitamins B6, B12, folate) was assessed in a subpopulation of women. Hcy and cysteine concentrations were progressively higher, and methionine was progressively lower across menopausal stages (all < 0.005). The higher Hcy and cysteine concentrations correlated with lower circulating estradiol levels ( = -0.49 and -0.50, respectively, both < 0.001). FMD was inversely correlated with Hcy ( = -0.25, = 0.004) and cysteine ( = -0.39, < 0.001) and positively correlated with methionine concentrations ( = 0.25, = 0.005). Dietary intake of vitamins B6 and B12 (both < 0.05) were lower in postmenopausal women. Vitamin B12 intake correlated with FMD ( = 0.22, = 0.006). These data suggest that declines in estradiol across stages of the menopause transition may lead to elevations in Hcy and cysteine that may contribute to endothelial dysfunction in postmenopausal women. Future studies should examine whether targeting Hcy metabolism during the perimenopausal to early postmenopausal period with interventions, including diet, attenuates or reverses the decline in endothelial function in women. Declines in circulating estradiol across the stages of the menopausal transition may lead to elevations in Hcy and cysteine concentrations that may contribute to endothelial dysfunction. Abnormalities in the Hcy metabolic pathways, possibly related to dietary deficiencies of vitamins B12 and B6 and folate, may contribute to elevations in Hcy and cysteine concentrations. Findings also suggest that higher cysteine levels may be more damaging to the vascular endothelium than Hcy.
高同型半胱氨酸血症与内皮功能障碍及心血管疾病（CVD）风险增加相关。我们研究了同型半胱氨酸（Hcy）升高及Hcy代谢标志物是否与先前报道的绝经过渡各阶段的内皮功能障碍有关。对年龄在22 - 70岁的128名健康女性进行了肱动脉血流介导的血管舒张功能（FMD）检测，并测定了她们血浆中Hcy、半胱氨酸和蛋氨酸的浓度。这些女性被分为绝经前（n = 35）、围绝经期（早期：n = 16；晚期：n = 21）和绝经后（早期：n = 21；晚期：n = 35）。对部分女性亚组评估了参与Hcy代谢的微量营养素（如维生素B6、B12、叶酸）的饮食摄入量。在绝经各阶段，Hcy和半胱氨酸浓度逐渐升高，而蛋氨酸浓度逐渐降低（均P < 0.005）。较高的Hcy和半胱氨酸浓度与较低的循环雌二醇水平相关（分别为r = -0.49和 -0.50，均P < 0.001）。FMD与Hcy（r = -0.25，P = 0.004）和半胱氨酸（r = -0.39，P < 0.001）呈负相关，与蛋氨酸浓度呈正相关（r = 0.25，P = 0.005）。绝经后女性维生素B6和B12的饮食摄入量较低（均P < 0.05）。维生素B12摄入量与FMD相关（r = 0.22，P = 0.006）。这些数据表明，绝经过渡各阶段雌二醇水平下降可能导致Hcy和半胱氨酸升高，这可能是绝经后女性内皮功能障碍的原因。未来研究应探讨在围绝经期至绝经后早期通过饮食等干预措施针对Hcy代谢是否可减轻或逆转女性内皮功能的下降。绝经过渡各阶段循环雌二醇水平下降可能导致Hcy和半胱氨酸浓度升高，这可能导致内皮功能障碍。Hcy代谢途径异常，可能与维生素B12、B6和叶酸的饮食缺乏有关，可能导致Hcy和半胱氨酸浓度升高。研究结果还表明较高的半胱氨酸水平可能比Hcy对血管内皮的损害更大。
