ArticleBlood2022
SOD2 V16A amplifies vascular dysfunction in sickle cell patients by curtailing mitochondria complex IV activity.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- The Important Role of Superoxide Dismutase 2 in Controlling Poxvirus Proliferation and Pathogenicity.Antioxidants (Basel, Switzerland) · 2026Article
- SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans.Scientific reports · 2025Article
- Mitochondrial Dysfunction in the Development and Progression of Cardiometabolic Diseases: A Narrative Review.Journal of clinical medicine · 2025Review
- Mitochondrial transfer in endothelial cells and vascular health.Trends in cell biology · 2025Review
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Identifying Water-Salt Homeostasis and Inflammatory Response in Pathological Cardiac Surgery-Associated Acute Kidney Injury: NT-proBNP-related lncRNAs and miRNAs as Novel Diagnostic Biomarkers and Therapeutic Targets.International journal of medical sciences · 2025Article
- Endurance training improves oxygen uptake/demand mismatch, metabolic flexibility and recovery in patients with sickle cell disease.Haematologica · 2024Article
- Article
- Flipping Off and On the Redox Switch in the Microcirculation.Annual review of physiology · 2023Review
- Endogenous SOD2 (Superoxide Dismutase) Regulates Platelet-Dependent Thrombin Generation and Thrombosis During Aging.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Sickle Cell Disease and Oxidative Stress: Implications for a Role of Diminished Endothelial SOD2 in Pulmonary Complications.Function (Oxford, England) · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Superoxide dismutase 2 (SOD2) catalyzes the dismutation of superoxide to hydrogen peroxide in mitochondria, limiting mitochondrial damage. The SOD2 amino acid valine-to-alanine substitution at position 16 (V16A) in the mitochondrial leader sequence is a common genetic variant among patients with sickle cell disease (SCD). However, little is known about the cardiovascular consequences of SOD2V16A in SCD patients or its impact on endothelial cell function. Here, we show SOD2V16A associates with increased tricuspid regurgitant velocity (TRV), systolic blood pressure, right ventricle area at systole, and declined 6-minute walk distance in 410 SCD patients. Plasma lactate dehydrogenase, a marker of oxidative stress and hemolysis, significantly associated with higher TRV. To define the impact of SOD2V16A in the endothelium, we introduced the SOD2V16A variant into endothelial cells. SOD2V16A increases hydrogen peroxide and mitochondrial reactive oxygen species (ROS) production compared with controls. Unexpectedly, the increased ROS was not due to SOD2V16A mislocalization but was associated with mitochondrial complex IV and a concomitant decrease in basal respiration and complex IV activity. In sum, SOD2V16A is a novel clinical biomarker of cardiovascular dysfunction in SCD patients through its ability to decrease mitochondrial complex IV activity and amplify ROS production in the endothelium.
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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.