Observational studyScientific reports2021
Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression.
Observational study in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Levels of ER Stress Markers GRP78, CHOP, and PERK in Cardiovascular Diseases.International journal of molecular sciences · 2026Article
- Iron Compartmentalisation and Vascular Endothelial Cell Dysfunction.Antioxidants (Basel, Switzerland) · 2026Review
- Effects of prosthetic heart valve-associated subclinical intravascular hemolysis on endothelium and cardiovascular system: a retrospective cohort study.Heart and vessels · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Mitochondrial Iron Handling and Lipid Peroxidation as Drivers of Ferroptosis.International journal of molecular sciences · 2026Review
- Heme as a Pro-Inflammatory Stimulus in Abdominal Aortic Aneurysm.Antioxidants (Basel, Switzerland) · 2026Article
- Article
- Heme-induced lung injury in human precision cut lung slices: a new model for acute lung injury.Respiratory research · 2025Article
- Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.Blood · 2025Article
- Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.Clinical rheumatology · 2024Article
- Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death.Journal of inflammation research · 2024Review
- Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human carotid artery plaques compared to healthy controls or atheromas without hemorrhage as demonstrated by RNA sequencing and immunohistochemistry. In EC cultures, heme also induces ER stress. In contrast, if cultured ECs are pulsed with heme arginate, cells become resistant to heme-induced ER (HIER) stress that is associated with heme oxygenase-1 (HO-1) and ferritin induction. Knocking down HO-1, HO-2, biliverdin reductase, and ferritin show that HO-1 is the ultimate cytoprotectant in acute HIER stress. Carbon monoxide-releasing molecules (CORMs) but not bilirubin protects cultured ECs from HIER stress via HO-1 induction, at least in part. Knocking down HO-1 aggravates heme-induced cell death that cannot be counterbalanced with any known cell death inhibitors. We conclude that endothelium and perhaps other cell types can be protected from HIER stress by induction of HO-1, and heme-induced cell death occurs via HIER stress that is potentially involved in the pathogenesis of diverse pathologies with hemolysis and hemorrhage including atherosclerosis.
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What OpenQuestion holds
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.