ArticleMicrocirculation (New York, N.Y. : 1994)2025
Oxidized Cell-Free Hemoglobin Induces Mitochondrial Dysfunction by Activation of the Mitochondrial Permeability Transition Pore in the Pulmonary Microvasculature.
Article in Microcirculation (New York, N.Y. : 1994), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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.
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Who cites it
4 citing papers in PubMed.
- Extracellular Hemoglobin, Hypoxia, and Macrophage-Mediated Pulmonary Vascular Remodeling in Hemolytic Disease.International journal of molecular sciences · 2026Review
- Early-life lung injury and the developing brain: a lung-brain axis perspective on neurodevelopmental disorders.Journal of neuroinflammation · 2026Review
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.Frontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectiveCell-free hemoglobin (CFH) is released into the circulation during sepsis where it can redox cycle from the ferrous 2+ to ferric 3+ and disrupt endothelial function, but the mechanisms of CF-mediated endothelial dysfunction are unknown. We hypothesized that oxidized CFH induces mitochondrial dysfunction via the mitochondrial permeability transition pore (mPTP) in pulmonary endothelial cells, leading to the release of mitochondrial DNA (mtDNA).
methodsHuman lung microvascular endothelial cells were treated with CFH2+/CFH3+. We measured mitochondrial mPTP activation (flow cytometry), network and mass (immunostaining), structure (electron microscopy), mtDNA release (PCR), and oxygen consumption rate (OCR; Seahorse). Plasma from critically ill patients and conditioned cell media were quantified for mtDNA and CFH.
resultsCFH3+ disrupted the mitochondrial network, activated the mPTP (1434 (874-1642) vs. 2302 (1729-2654) mean fluorescent intensity, p = 0.02), increased the spare respiratory capacity (30.61 (29.36-37.78) vs. 7.83 (3.715-10.63) OCR, p = 0.004), and caused the release of mtDNA. CFH was associated with circulating mtDNA (R
conclusionCFH3+, not CFH2+, is the primary driver of CFH-induced lung microvascular mitochondrial dysfunction. Activation of the mPTP and the release of mtDNA are a feature of CFH3+ mediated injury.
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