Zhou Ke, Xiao Jun, Wang Hao, Ni Bing, Huang Jietao, Long Xueyuan
Vasculocardiology Department, Chongqing University Central Hospital, Chongqing, 400014, China.
Institute of Immunology of Army Medical University, Chongqing, 400014, China.
Heliyon. 2023 Mar 4;9(3):e14305. doi: 10.1016/j.heliyon.2023.e14305. eCollection 2023 Mar.
Cardiovascular diseases remain the leading cause of death, morbidity, and disability. Recently, it has been reported that gonadal hormones such as estradiol can act on membrane receptors and activate intracellular signaling mechanisms, thereby altering cellular function. This study aims to explore the function and molecular mechanism of estradiol on cardiac microvascular endothelial cells (CMVECs). Estradiol had low toxicity to CMVECs. Hypoxia/reoxygenation (H/R) stimulation inhibited the proliferation and migration of CMVECs, while estradiol significantly promoted proliferation and migration. Estradiol inhibited il-1, IL6, and TNF-α secretion levels after H/R stimulation. Meanwhile, estradiol inhibits oxidative stress and promotes angiogenesis. Further, estradiol upregulated the gene and protein levels of cyclin-dependent kinases 1 (CDK1) and CDK2 after H/R stimulation. When knocking down CDK1 and CDK2 of CMVECs, estradiol did not affect the protein expression of Cyclin E1 and Cyclin D1. Meanwhile, the regulatory effect of estradiol on oxidative stress, angiogenesis, and inflammatory response was significantly weakened or even disappeared. In conclusion, estradiol mediates oxidative stress and angiogenesis of myocardial microvascular endothelial cells by regulating the CDK/cyclin signaling pathway.
心血管疾病仍然是导致死亡、发病和残疾的主要原因。最近，有报道称，雌二醇等性腺激素可作用于膜受体并激活细胞内信号传导机制，从而改变细胞功能。本研究旨在探讨雌二醇对心脏微血管内皮细胞（CMVECs）的作用及其分子机制。雌二醇对CMVECs的毒性较低。缺氧/复氧（H/R）刺激抑制了CMVECs的增殖和迁移，而雌二醇则显著促进了其增殖和迁移。雌二醇抑制了H/R刺激后白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的分泌水平。同时，雌二醇抑制氧化应激并促进血管生成。此外，雌二醇在H/R刺激后上调了细胞周期蛋白依赖性激酶1（CDK1）和细胞周期蛋白依赖性激酶2（CDK2）的基因和蛋白水平。当敲低CMVECs的CDK1和CDK2时，雌二醇不影响细胞周期蛋白E1（Cyclin E1）和细胞周期蛋白D1（Cyclin D1）的蛋白表达。同时，雌二醇对氧化应激、血管生成和炎症反应的调节作用显著减弱甚至消失。综上所述，雌二醇通过调节CDK/细胞周期蛋白信号通路介导心肌微血管内皮细胞的氧化应激和血管生成。
