Bedreag Ovidiu

Borza Claudia

Burghelea Radu N.

Bînă Anca-Mihaela

Bînă Paul

Crețu Octavian M.

Muntean Danina M.

Neagu Adrian

Paraschivoiu Anca

Săndesc Dorel

English

University of Szeged

 97  8th European Section Meeting of the International Academy of Cardiovascular Sciences (IACS); September 28 – October 1, 2022; Szeged, Hungary CELL- PERMEABLE SUCCINATE RESCUES PLATELET MITOCHONDRIAL RESPIRATION IN COVID-19 PATIENTS   Paul Bînă1, Radu N. Burghelea2, Anca M. Bînă3,4, Anca Paraschivoiu5, Ovidiu Bedreag6, Dorel Săndesc6, Claudia Borza3,4, Adrian Neagu7, Octavian M. Crețu8, Danina M. Muntean3,4  1Doctoral School Medicine-Pharmacy, ”Victor Babeș" University of Medicine and Pharmacy Timișoara; Clinic of Anaesthesia and Intensive Care, "Pius Brînzeu" Emergency County Hospital, Timișoara, Romania 2Emergency City Hospital, Clinic of Anaesthesia and Intensive Care, Timișoara, Romania 3Department III - Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania 4Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania 5Dr. Victor Popescu” Military Emergency Hospital, Timișoara, Romania 6Department X - Anaesthesia and Intensive Care, "Victor Babeș" University of Medicine and Pharmacy Timișoara; Clinic of Anaesthesia and Intensive Care, "Pius Brînzeu" Emergency County Hospital Timișoara, Romania 7Department III - Biophysics, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania 8Department IX - Surgical Semiotics 1, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania  The COVID-19 pandemic remains a global health issue since its outbreak. Hyperinflammation with “cytokine storm”, endothelial dysfunction, and more recently, mitochondrial dysfunction were identified as main pathomechanisms. Platelet respiratory dysfunction has recently emerged as a peripheral biomarker that could mirror organ mitochondrial dysfunction. NV118, a cell-permeable succinate, is a new prodrug able to support mitochondrial function by enhancing complex II-supported respiration.   The present pilot study performed in platelets harvested from patients hospitalized for various forms of SARS-CoV2 infection was double-aimed: i) to assess the mitochondrial respiratory dysfunction; ii) to investigate whether NV118 can rescue it. Nineteen patients with moderate (n=5) and severe (n=14) disease were included. Peripheral blood was collected and used for platelet isolation. Platelet respiration was measured at 37°C using high-resolution respirometry according to a SUIT protocol for permeabilized platelets allowing the measurement of the following respiratory parameters: routine, active, non-phosphorylating and maximal uncoupled respiration. Intact platelets (n=15) were acutely exposed to NV118 (vs DMSO) and routine, leak and maximal uncoupled respiration were measured. The severe forms of disease expressed a significant decrease in platelet active respiration for both respiratory complexes and an increase of routine, leak and uncoupled respiration. Moderate forms of disease present only a significant decrease in active respiration, particularly for CI. Cell-permeable succinate elicited a significant increase in routine, leak and maximal uncoupled respiration for both mitochondrial complexes.  In conclusion, COVID-19 differentially impairs platelet bioenergetics, according to the severity of the disease, eliciting mitochondrial respiratory dysfunction that can be rescued by cell-permeable succinate.   Keywords: COVID-19, platelets, mitochondria, high-resolution respirometry, cell-permeable succinate    

Cell-permeable succinate rescues platelet mitochondrial respiration in COVID-19 patients : [abstract]

http://acta.bibl.u-szeged.hu/77557/1/iacs_es_2022_097.pdf

Cell-permeable succinate rescues platelet mitochondrial respiration in COVID-19 patients : [abstract]

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