同卵双胞胎脐静脉内皮细胞的性别特异性代谢和功能差异。
Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs.
机构信息
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany.
Institut für Chemie und Biochemie, Freie Universität Berlin, Germany; Berlin School of Integrative Oncology (DFG Graduate School 1093), Germany.
出版信息
Atherosclerosis. 2019 Dec;291:99-106. doi: 10.1016/j.atherosclerosis.2019.10.007. Epub 2019 Oct 10.
BACKGROUND AND AIMS
Gonadal hormones are mainly thought to account for sex and gender differences in the incidence, clinical manifestation and therapy of many cardiovascular diseases. However, intrinsic sex differences at the cellular level are mostly overlooked. Here, we assessed sex-specific metabolic and functional differences between male and female human umbilical vein endothelial cells (HUVECs).
METHODS
Cellular metabolism was investigated by bioenergetic studies (Seahorse Analyser) and a metabolomic approach. Protein levels were determined by Western blots and proteome analysis. Vascular endothelial growth factor (VEGF)-stimulated cellular migration was assessed by gap closure. HUVECs from dizygotic twin pairs were used for most experiments.
RESULTS
No sex differences were observed in untreated cells. However, sexual dimorphisms appeared after stressing the cells by serum starvation and treatment with VEGF. Under both conditions, female cells had higher intracellular ATP and metabolite levels. A significant decline in ATP levels was observed in male cells after serum starvation. After VEGF, the ratio of glycolysis/mitochondrial respiration was higher in female cells and migration was more pronounced.
CONCLUSIONS
These results point to an increased stress tolerance of female cells. We therefore propose that female cells have an energetic advantage over male cells under conditions of diminished nutrient supply. A more favourable energy balance of female HUVECs after serum starvation and VEGF could potentially explain their stronger migratory capacity.
背景与目的
性腺激素被认为主要导致许多心血管疾病的发病率、临床表现和治疗存在性别和性别差异。然而，细胞水平上的内在性别差异在很大程度上被忽视了。在这里，我们评估了男性和女性人脐静脉内皮细胞（HUVEC）之间的特定于性别的代谢和功能差异。
方法
通过生物能量学研究（ Seahorse 分析仪）和代谢组学方法研究细胞代谢。通过 Western blot 和蛋白质组分析测定蛋白质水平。通过缝隙封闭评估血管内皮生长因子（VEGF）刺激的细胞迁移。大多数实验使用来自同卵双胞胎的 HUVEC。
结果
未处理的细胞中未观察到性别差异。然而，在通过血清饥饿和 VEGF 处理使细胞紧张后，出现了性别二态性。在这两种情况下，女性细胞的细胞内 ATP 和代谢物水平都更高。血清饥饿后，男性细胞中的 ATP 水平显着下降。在 VEGF 之后，女性细胞中的糖酵解/线粒体呼吸比率更高，迁移更为明显。
结论
这些结果表明女性细胞的应激耐受性更高。因此，我们提出，在营养供应减少的情况下，女性细胞比男性细胞具有更高的能量优势。血清饥饿和 VEGF 后，女性 HUVEC 的能量平衡更为有利，这可能解释了它们更强的迁移能力。
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