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Peer-reviewedCC BYJournal of cardiovascular development and disease

Altered Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Coupling and Complex IV Respiration in Severe Aortic Stenosis Before and After Transcatheter Aortic Valve Replacement (TAVR).

5 affiliations
  1. 1Cardiology Department, Strasbourg University Hospital, 1 Place de L'Hôpital, 67000 Strasbourg, France.
  2. 2UR 3072, "Mitochondria, Oxidative Stress and Muscle Plasticity", Biomedicine Research Center of Strasbourg (CRBS), Faculty of Medicine, University of Strasbourg, 67000 Strasbourg, France.
  3. 3Department of Physiology and Functional Explorations, Strasbourg University Hospital, 67000 Strasbourg, France.
  4. 4Cardiac Surgery Department, Strasbourg University Hospital, 1 Place de L'Hôpital, 67000 Strasbourg, France.
  5. 5FMTS, Biomedicine Research Center of Strasbourg, UR 3074, Translational Cardiovascular Medicine, University of Strasbourg, 1 Rue Eugène Boeckel, 67000 Strasbourg, France.

Abstract

Background

Circulating peripheral blood mononuclear cell (PBMC) mitochondrial respiration is impaired in heart failure and transplanted patients. Severe aortic stenosis (AS), characterized by pressure overload leading to cardiac mitochondrial dysfunction, might also be associated with PBMC mitochondrial respiration alterations, likely related to systemic inflammation and left heart hypertrophy and diastolic dysfunction.Population and methods

We determined PBMC mitochondrial respiration by high-resolution respirometry (Oroboros Instruments) in 9 healthy subjects and 25 AS patients before and until 30 days after transcatheter aortic valve replacement (TAVR) and investigated potential correlates with the clinical, biological and echocardiographic characteristics of the patients.Results

AS patients with a transaortic valvular gradient of 45 mm Hg were older and demonstrated slightly impaired renal function, inflammation markers, increased brain natriuretic peptide, left ventricular hypertrophy, and impaired diastolic function. PBMC mitochondrial coupling was decreased in the AS patients compared to controls (2.12 ± 0.10 vs. 2.76 ± 0.17, p = 0.003) and mitochondrial complex IV respiration was increased (31.07 ± 2.84 vs. 18.69 ± 2.09, p = 0.017). TAVR did not modify the alterations. Interestingly, increased complex IV mitochondrial respiration was associated with reduced mortality (p < 0.01).Conclusions

Severe aortic stenosis is associated with bioenergetic remodeling of circulating mononuclear cells that were not significantly associated with valvular hemodynamic impairment and ventricular function, before and after the mechanical relief of afterload. Nevertheless, future studies will be useful to determine whether such systemic immuno-metabolic phenotype, particularly PBMC mitochondrial complex IV respiration stimulation, may contribute to reduce the risk following TAVR.

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BibTeX
@article{marchandot2026altered,
  title = {{Altered Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Coupling and Complex IV Respiration in Severe Aortic Stenosis Before and After Transcatheter Aortic Valve Replacement (TAVR).}},
  author = {Benjamin Marchandot and Anne-Laure Charles and Kerem Demir and Cedric Momas and Samy Talha and Michel Kindo and Patrick Ohlmann and Margherita Giannini and Alain Meyer and Olivier Morel and Bernard Geny},
  journal = {Journal of cardiovascular development and disease},
  year = {2026},
  month = sep,
  doi = {10.3390/jcdd13100480},
  url = {https://europepmc.org/article/MED/42930876},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Altered Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Coupling and Complex IV Respiration in Severe Aortic Stenosis Before and After Transcatheter Aortic Valve Replacement (TAVR).
AU  - Benjamin Marchandot
AU  - Anne-Laure Charles
AU  - Kerem Demir
AU  - Cedric Momas
AU  - Samy Talha
AU  - Michel Kindo
AU  - Patrick Ohlmann
AU  - Margherita Giannini
AU  - Alain Meyer
AU  - Olivier Morel
AU  - Bernard Geny
PY  - 2026
DA  - 2026/09/23
JO  - Journal of cardiovascular development and disease
DO  - 10.3390/jcdd13100480
UR  - https://europepmc.org/article/MED/42930876
AB  - Background  Circulating peripheral blood mononuclear cell (PBMC) mitochondrial respiration is impaired in heart failure and transplanted patients. Severe aortic stenosis (AS), characterized by pressure overload leading to cardiac mitochondrial dysfunction, might also be associated with PBMC mitochondrial respiration alterations, likely related to systemic inflammation and left heart hypertrophy and diastolic dysfunction.Population and methods  We determined PBMC mitochondrial respiration by high-resolution respirometry (Oroboros Instruments) in 9 healthy subjects and 25 AS patients before and until 30 days after transcatheter aortic valve replacement (TAVR) and investigated potential correlates with the clinical, biological and echocardiographic characteristics of the patients.Results  AS patients with a transaortic valvular gradient of 45 mm Hg were older and demonstrated slightly impaired renal function, inflammation markers, increased brain natriuretic peptide, left ventricular hypertrophy, and impaired diastolic function. PBMC mitochondrial coupling was decreased in the AS patients compared to controls (2.12 ± 0.10 vs. 2.76 ± 0.17, p = 0.003) and mitochondrial complex IV respiration was increased (31.07 ± 2.84 vs. 18.69 ± 2.09, p = 0.017). TAVR did not modify the alterations. Interestingly, increased complex IV mitochondrial respiration was associated with reduced mortality (p < 0.01).Conclusions  Severe aortic stenosis is associated with bioenergetic remodeling of circulating mononuclear cells that were not significantly associated with valvular hemodynamic impairment and ventricular function, before and after the mechanical relief of afterload. Nevertheless, future studies will be useful to determine whether such systemic immuno-metabolic phenotype, particularly PBMC mitochondrial complex IV respiration stimulation, may contribute to reduce the risk following TAVR.
SN  - 2308-3425
ER  -