ArticleCell death and differentiation2018
Heme accumulation in endothelial cells impairs angiogenesis by triggering paraptosis.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 98 citations in OpenAlex.
- Effects of argon plasma treatment on the osteoconductivity of bone grafting materials.Clinical oral investigations · 2020Trial
- Tramadol induced hypoxia signaling and paraptosis-like cell death in breast cancer cells via HIF-1α and ATF4 dependent pathways.Redox report : communications in free radical research · 2026Article
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis.Science advances · 2026Article
- Heterogeneous CRISPR/Cas9 Editing ofInternational journal of molecular sciences · 2026Article
- FLVCR2 Regulation of Intracellular Heme Modulates Vascular Tip/Stalk Specification During Retinal Angiogenesis.Investigative ophthalmology & visual science · 2026Article
- More than a ring: the emerging role of heme in angiogenesis.Cell communication and signaling : CCS · 2026Review
- Distinct types of regulated cell death in atherosclerosis.Journal of pharmaceutical analysis · 2026Review
- Exploiting porphyrin metabolism to inhibit angiogenesis.Angiogenesis · 2026Article
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- FLVCR1-related diseases: from clinical heterogeneity to mechanistic insights.Brain communications · 2026Review
- Heme drives cardiac endothelial senescence in sepsis via STING activation.Cell death & disease · 2025Article
- SHP2-mediated ROS activation induces chondrocyte paraptosis in osteoarthritis and is attenuated by low-intensity pulsed ultrasound.Journal of orthopaedic translation · 2025Article
- Heme-induced lung injury in human precision cut lung slices: a new model for acute lung injury.Respiratory research · 2025Article
- Exploring paraptosis as a therapeutic approach in cancer treatment.Journal of biomedical science · 2024Review
- Paraptosis-A Distinct Pathway to Cell Death.International journal of molecular sciences · 2024Review
- Raman imaging unveils heme uptake in endothelial cells.Scientific reports · 2024Article
- Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.Cell reports. Medicine · 2024Article
- Unearthing FLVCR1a: tracing the path to a vital cellular transporter.Cellular and molecular life sciences : CMLS · 2024Review
- Targeting paraptosis in cancer: opportunities and challenges.Cancer gene therapy · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme is required for cell respiration and survival. Nevertheless, its intracellular levels need to be finely regulated to avoid heme excess, which may catalyze the production of reactive oxygen species (ROS) and promote cell death. Here, we show that alteration of heme homeostasis in endothelial cells due to the loss of the heme exporter FLVCR1a, results in impaired angiogenesis. In vitro, FLVCR1a silencing in endothelial cells causes defective tubulogenesis and poor viability due to intracellular heme accumulation. Consistently, endothelial-specific Flvcr1a knockout mice show aberrant angiogenesis responsible for hemorrhages and embryonic lethality. Importantly, we demonstrate that impaired heme export leads to endothelial cell death by paraptosis and provide evidence that endoplasmic reticulum (ER) stress precedes heme-induced paraptosis. These findings highlight a crucial role for the cytosolic heme pool in the control of endothelial cell survival and in the regulation of the angiogenic process. Interfering with endothelial heme export represents a valuable model for a deeper understanding of the molecular mechanisms underlying heme-triggered paraptosis and, in the future, might provide a novel tool for the modulation of angiogenesis in pathophysiologic conditions.
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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.