ArticleThe Journal of biological chemistry2017
Estrogen receptor β-dependent Notch1 activation protects vascular endothelium against tumor necrosis factor α (TNFα)-induced apoptosis.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Sexually dimorphic role of estrogen receptor α in preserving right ventricular endothelial integrity.bioRxiv : the preprint server for biology · 2025Article
- Multifaceted Role of Notch Signaling in Vascular Health and Diseases.Biomedicines · 2025Review
- Menopause mysteries: the exosome-inflammation connection.Journal of ovarian research · 2025Review
- 17β-estradiol inhibits Notch1 activation in murine macrophage cell line RAW 264.7.Molecular biology reports · 2024Article
- Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.Current medical science · 2024Review
- Single-cell RNA reveals a tumorigenic microenvironment in the interface zone of human breast tumors.Breast cancer research : BCR · 2023Article
- Kindlin-2 controls angiogenesis through modulating Notch1 signaling.Cellular and molecular life sciences : CMLS · 2023Article
- Caveolin-1 inhibition mediates the opposing effects of alcohol on γ-secretase activity in arterial endothelial and smooth muscle cells.Physiological reports · 2023Article
- Estrogen receptor beta activity contributes to both tumor necrosis factor alpha expression in the hypothalamic paraventricular nucleus and the resistance to hypertension following angiotensin II in female mice.Neurochemistry international · 2022Article
- Agri-Food Waste from Apple, Pear, and Sugar Beet as a Source of Protective Bioactive Molecules for Endothelial Dysfunction and Its Major Complications.Antioxidants (Basel, Switzerland) · 2022Review
- Pathophysiology and risk factors of peripartum cardiomyopathy.Nature reviews. Cardiology · 2022Review
- Inflammation and atherosclerosis: signaling pathways and therapeutic intervention.Signal transduction and targeted therapy · 2022Review
- Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart.Open life sciences · 2022Article
- Article
- Oestradiol promotes the intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via Notch signalling pathway.Journal of cellular and molecular medicine · 2021Article
- Article
- Well-Known and Novel Players in Endothelial Dysfunction: Updates on a Notch(ed) Landscape.Biomedicines · 2021Review
- Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective.Frontiers in cell and developmental biology · 2021Review
- Adding a "Notch" to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach.Frontiers in cell and developmental biology · 2021Review
- Mechanobiology of Microvascular Function and Structure in Health and Disease: Focus on the Coronary Circulation.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Unlike age-matched men, premenopausal women benefit from cardiovascular protection. Estrogens protect against apoptosis of endothelial cells (ECs), one of the hallmarks of endothelial dysfunction leading to cardiovascular disorders, but the underlying molecular mechanisms remain poorly understood. The inflammatory cytokine TNFα causes EC apoptosis while dysregulating the Notch pathway, a major contributor to EC survival. We have previously reported that 17β-estradiol (E2) treatment activates Notch signaling in ECs. Here, we sought to assess whether in TNFα-induced inflammation Notch is involved in E2-mediated protection of the endothelium. We treated human umbilical vein endothelial cells (HUVECs) with E2, TNFα, or both and found that E2 counteracts TNFα-induced apoptosis. When Notch1 was inhibited, this E2-mediated protection was not observed, whereas ectopic overexpression of Notch1 diminished TNFα-induced apoptosis. Moreover, TNFα reduced the levels of active Notch1 protein, which were partially restored by E2 treatment. Moreover, siRNA-mediated knockdown of estrogen receptor β (ERβ), but not ERα, abolished the effect of E2 on apoptosis. Additionally, the E2-mediated regulation of the levels of active Notch1 was abrogated after silencing ERβ. In summary, our results indicate that E2 requires active Notch1 through a mechanism involving ERβ to protect the endothelium in TNFα-induced inflammation. These findings could be relevant for assessing the efficacy and applicability of menopausal hormone treatment, because they may indicate that in women with impaired Notch signaling, hormone therapy might not effectively protect the endothelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.