Persistent Monocytic Bioenergetic Impairment and Mitochondrial DNA Damage in PASC Patients with Cardiovascular Complications DOI Open Access
Dilvin Semo,

Zornitsa Shomanova,

Jürgen Sindermann

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4562 - 4562

Published: May 9, 2025

Cardiovascular complications are a hallmark of Post-Acute Sequelae Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial in immune cells as key contributor. This study investigated whether CD14++ monocytes from long COVID patients exhibit bioenergetic impairment, DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms PASC. were isolated 14 with (e.g., dyspnea, angina) 10 age-matched controls similar risk profiles. Mitochondrial function was assessed using Seahorse Agilent Analyzer under basal conditions after induction buthionine sulfoximine (BSO). membrane potential measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity qPCR, reactive oxygen species (ROS) dynamics Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy to SARS-CoV-2 spike protein evaluate direct viral effects. (n = 14) exhibited profound compared 10). Under induced by (BSO), failed upregulate respiration (9.5 vs. 30.4 pmol/min controls, p 0.0043), showed 65% reduction maximal (p 0.4035, ns) demonstrated 70% loss spare respiratory capacity 0.4143, significantly impaired adaptation BSO challenge (long + BSO: 9.9 control 54 pmol/min, 0.0091). Proton leak, protective mechanism against ROS overproduction, blunted (3-fold 13-fold elevation 0.0294). Paradoxically, reduced accumulation treatment (6% decrease 1.2-fold increase 0.0015) elevated (157 113.7 TMRE fluorescence, 0.0179), remained stable stress. analysis revealed severe depletion (80% reduction, < 0.001) region-specific 75% reductions amplification efficiency for regions C D 0.05), respectively. In contrast, exposure did not recapitulate these defects, preserved respiration, ATP production, capacity, though coupling 0.05). These findings suggest that syndrome arises maladaptive host responses rather than toxicity, characterized failure, genomic instability. identifies critical driver Key defects—bioenergetic damage—correlate clinical like heart failure exercise intolerance. The resistance remodeling physiology. position resilience therapeutic target, strategies including antioxidants, repair agents or metabolic modulators. dissociation between highlights need explore host-directed PASC pathophysiology. work advances our understanding sequelae provides foundation biomarker development targeted interventions mitigate long-term morbidity.

Language: Английский

Persistent Monocytic Bioenergetic Impairment and Mitochondrial DNA Damage in PASC Patients with Cardiovascular Complications DOI Open Access
Dilvin Semo,

Zornitsa Shomanova,

Jürgen Sindermann

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4562 - 4562

Published: May 9, 2025

Cardiovascular complications are a hallmark of Post-Acute Sequelae Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial in immune cells as key contributor. This study investigated whether CD14++ monocytes from long COVID patients exhibit bioenergetic impairment, DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms PASC. were isolated 14 with (e.g., dyspnea, angina) 10 age-matched controls similar risk profiles. Mitochondrial function was assessed using Seahorse Agilent Analyzer under basal conditions after induction buthionine sulfoximine (BSO). membrane potential measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity qPCR, reactive oxygen species (ROS) dynamics Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy to SARS-CoV-2 spike protein evaluate direct viral effects. (n = 14) exhibited profound compared 10). Under induced by (BSO), failed upregulate respiration (9.5 vs. 30.4 pmol/min controls, p 0.0043), showed 65% reduction maximal (p 0.4035, ns) demonstrated 70% loss spare respiratory capacity 0.4143, significantly impaired adaptation BSO challenge (long + BSO: 9.9 control 54 pmol/min, 0.0091). Proton leak, protective mechanism against ROS overproduction, blunted (3-fold 13-fold elevation 0.0294). Paradoxically, reduced accumulation treatment (6% decrease 1.2-fold increase 0.0015) elevated (157 113.7 TMRE fluorescence, 0.0179), remained stable stress. analysis revealed severe depletion (80% reduction, < 0.001) region-specific 75% reductions amplification efficiency for regions C D 0.05), respectively. In contrast, exposure did not recapitulate these defects, preserved respiration, ATP production, capacity, though coupling 0.05). These findings suggest that syndrome arises maladaptive host responses rather than toxicity, characterized failure, genomic instability. identifies critical driver Key defects—bioenergetic damage—correlate clinical like heart failure exercise intolerance. The resistance remodeling physiology. position resilience therapeutic target, strategies including antioxidants, repair agents or metabolic modulators. dissociation between highlights need explore host-directed PASC pathophysiology. work advances our understanding sequelae provides foundation biomarker development targeted interventions mitigate long-term morbidity.

Language: Английский

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