ArticleAntioxidants & redox signaling2014
Nrf2 regulates angiogenesis: effect on endothelial cells, bone marrow-derived proangiogenic cells and hind limb ischemia.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 116 citations in OpenAlex.
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- Targeted KEAP1 disruption enhances antioxidant defense and mesenchymal stromal cell therapy for chronic limb-threatening ischemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Nrf2 regulates angiogenesis in spinal cystic echinococcosis via RTN4.Microbiology spectrum · 2026Article
- Oxidative Stress and the KEAP1/NRF2 Axis in Saphenous Vein: Implications for Graft Patency.Cells · 2026Review
- Inhibition of smooth muscle phenotypic modulation by bardoxolone methyl, omaveloxolone, and cinnamaldehyde is Nrf-2 dependent.Advances in redox research · 2026Article
- Multifunctional pectin derivatives as anticancer agents in colorectal cancer via synthesis, computational insights, and modulation of NRF2/HO-1, HIF-1α, and VEGF/PDGF-D signaling pathways.Scientific reports · 2026Article
- Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease.Antioxidants & redox signaling · 2025Review
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- PLZF promotes compensatory lung growth by increasing HPMEC proliferation and angiogenesis.PloS one · 2025Article
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- Dysregulated VEGF/VEGFR-2 Signaling and Plexogenic Lesions in the Embryonic Lungs of Chickens Predisposed to Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Article
- Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.Experimental & molecular medicine · 2024Review
- Angiogenic potential of skeletal muscle derived extracellular vesicles differs between oxidative and glycolytic muscle tissue in mice.Scientific reports · 2023Article
- Fucoidan promotes angiogenesis and accelerates wound healing through AKT/Nrf2/HIF-1α signalling pathway.International wound journal · 2023Article
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- Harnessing the cardiovascular benefits of exercise: Are Nrf2 activators useful?Sports medicine and health science · 2021Review
- NRF2 is a key regulator of endothelial microRNA expression under proatherogenic stimuli.Cardiovascular research · 2021Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsNuclear factor E2-related factor 2 (Nrf2), a key cytoprotective transcription factor, regulates also proangiogenic mediators, interleukin-8 and heme oxygenase-1 (HO-1). However, hitherto its role in blood vessel formation was modestly examined. Particularly, although Nrf2 was shown to affect hematopoietic stem cells, it was not tested in bone marrow-derived proangiogenic cells (PACs). Here we investigated angiogenic properties of Nrf2 in PACs, endothelial cells, and inflammation-related revascularization.
resultsTreatment of endothelial cells with angiogenic cytokines increased nuclear localization of Nrf2 and induced expression of HO-1. Nrf2 activation stimulated a tube network formation, while its inhibition decreased angiogenic response of human endothelial cells, the latter effect reversed by overexpression of HO-1. Moreover, lack of Nrf2 attenuated survival, proliferation, migration, and angiogenic potential of murine PACs and affected angiogenic transcriptome in vitro. Additionally, angiogenic capacity of PAC Nrf2(-/-) in in vivo Matrigel assay and PAC mobilization in response to hind limb ischemia of Nrf2(-/-) mice were impaired. Despite that, restoration of blood flow in Nrf2-deficient ischemic muscles was better and accompanied by increased oxidative stress and inflammatory response. Accordingly, the anti-inflammatory agent etodolac tended to diminish blood flow in the Nrf2(-/-) mice. INNOVATION: Identification of a novel role of Nrf2 in angiogenic signaling of endothelial cells and PACs.
conclusionNrf2 contributes to angiogenic potential of both endothelial cells and PACs; however, its deficiency increases muscle blood flow under tissue ischemia. This might suggest a proangiogenic role of inflammation in the absence of Nrf2 in vivo, concomitantly undermining the role of PACs in such conditions.
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