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 t...

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Main Authors: Ke Zhou, Jun Xiao, Hao Wang, Bing Ni, Jietao Huang, Xueyuan Long
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023015128
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author Ke Zhou
Jun Xiao
Hao Wang
Bing Ni
Jietao Huang
Xueyuan Long
author_facet Ke Zhou
Jun Xiao
Hao Wang
Bing Ni
Jietao Huang
Xueyuan Long
author_sort Ke Zhou
collection DOAJ
description 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.
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spelling doaj.art-6c87be48afeb487b816ba3c0628b86262023-04-05T08:23:01ZengElsevierHeliyon2405-84402023-03-0193e14305Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathwayKe Zhou0Jun Xiao1Hao Wang2Bing Ni3Jietao Huang4Xueyuan Long5Vasculocardiology Department, Chongqing University Central Hospital, Chongqing, 400014, ChinaVasculocardiology Department, Chongqing University Central Hospital, Chongqing, 400014, China; Corresponding author.Vasculocardiology Department, Chongqing University Central Hospital, Chongqing, 400014, ChinaInstitute of Immunology of Army Medical University, Chongqing, 400014, ChinaVasculocardiology Department, Chongqing University Central Hospital, Chongqing, 400014, ChinaVasculocardiology Department, Chongqing University Central Hospital, Chongqing, 400014, ChinaCardiovascular 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.http://www.sciencedirect.com/science/article/pii/S2405844023015128Cardiovascular diseasesEstradiolCDKOxidative stressAngiogenesis
spellingShingle Ke Zhou
Jun Xiao
Hao Wang
Bing Ni
Jietao Huang
Xueyuan Long
Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway
Heliyon
Cardiovascular diseases
Estradiol
CDK
Oxidative stress
Angiogenesis
title Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway
title_full Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway
title_fullStr Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway
title_full_unstemmed Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway
title_short Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway
title_sort estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the cdk1 cdk2 pathway
topic Cardiovascular diseases
Estradiol
CDK
Oxidative stress
Angiogenesis
url http://www.sciencedirect.com/science/article/pii/S2405844023015128
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