Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway.

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.