ArticleBlood2020
Heme induces rapid endothelial barrier dysfunction via the MKK3/p38MAPK axis.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 33 citations in OpenAlex.
- Biologic Mechanisms Underlying the Heterogeneous Response to Tight Glycemic Control among Differentially Inflamed Patients in the HALF-PINT Trial.American journal of respiratory and critical care medicine · 2025Trial
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Mitigating sepsis-induced vascular endothelial dysfunction through Niban phosphorylation.Vascular medicine (London, England) · 2026Article
- Heme-mediated Tau phosphorylation drives neurocognitive responses in sickle cell disease.Blood red cells & iron · 2026Article
- Distinct populations of lung capillary endothelial cells and their functional significance.Communications biology · 2025Article
- Mitochondrial dysfunction-induced hemolysis: a precursor to vascular leakage and pulmonary hypertension.Blood vessels, thrombosis & hemostasis · 2025Article
- Myocardial infarction induces endothelial dysfunction with independence of cardiovascular risk factors.Angiogenesis · 2025Article
- Red blood cell extracellular vesicles: new frontiers in hematological biomarker discovery.Frontiers in medicine · 2025Review
- Circulating free heme induces cytokine storm and pulmonary hypertension through the MKK3/p38 axis.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Regulatory effects of the p38 mitogen-activated protein kinase-myosin light chain kinase pathway on the intestinal epithelial mechanical barrier and the mechanism of modified Pulsatilla decoction in the treatment of ulcerative colitis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome.Journal of inflammation research · 2024Article
- Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death.Journal of inflammation research · 2024Review
- Novel Populations of Lung Capillary Endothelial Cells and Their Functional Significance.Research square · 2023Article
- Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injuryActa pharmaceutica Sinica. B · 2023Article
- Article
- Cortactin loss protects against hemin-induced acute lung injury in sickle cell disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- HSPB1 Regulates Autophagy and Apoptosis in Vascular Smooth Muscle Cells in Arteriosclerosis Obliterans.Cardiovascular therapeutics · 2022Article
- Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats.PloS one · 2022Article
- A novel intronic circular RNA, circGNG7, inhibits head and neck squamous cell carcinoma progression by blocking the phosphorylation of heat shock protein 27 at Ser78 and Ser82.Cancer communications (London, England) · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Several studies demonstrate that hemolysis and free heme in circulation cause endothelial barrier dysfunction and are associated with severe pathological conditions such as acute respiratory distress syndrome, acute chest syndrome, and sepsis. However, the precise molecular mechanisms involved in the pathology of heme-induced barrier disruption remain to be elucidated. In this study, we investigated the role of free heme in the endothelial barrier integrity and mechanisms of heme-mediated intracellular signaling of human lung microvascular endothelial cells (HLMVECs). Heme, in a dose-dependent manner, induced a rapid drop in the endothelial barrier integrity of HLMVECs. An investigation into barrier proteins revealed that heme primarily affected the tight junction proteins zona occludens-1, claudin-1, and claudin-5, which were significantly reduced after heme exposure. The p38MAPK/HSP27 pathway, involved in the regulation of endothelial cytoskeleton remodeling, was also significantly altered after heme treatment, both in HLMVECs and mice. By using a knockout (KO) mouse for MKK3, a key regulator of the p38MAPK pathway, we showed that this KO effectively decreased heme-induced endothelial barrier dysfunction. Taken together, our results indicate that targeting the p38MAPK pathway may represent a crucial treatment strategy in alleviating hemolytic diseases.
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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 Socratic graph.