Improvement of Platelet Respiration by Cell–Permeable Succinate in Diabetic Patients Treated with Statins
Vlad Florian Avram,
Anca Mihaela Bîna,
Alexandra Sima,
Oana Maria Aburel,
Adrian Sturza,
Ovidiu Burlacu,
Romulus Zorin Timar,
Danina Mirela Muntean,
Eskil Elmér,
Octavian Marius Crețu
Affiliations
Vlad Florian Avram
Department VII Internal Medicine—Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Anca Mihaela Bîna
Center for Translational Research and Systems Medicine, ”Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Alexandra Sima
Department VII Internal Medicine—Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Oana Maria Aburel
Center for Translational Research and Systems Medicine, ”Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Adrian Sturza
Center for Translational Research and Systems Medicine, ”Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Ovidiu Burlacu
Department IX Surgery—Surgical Semiotics I, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Romulus Zorin Timar
Department VII Internal Medicine—Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Danina Mirela Muntean
Center for Translational Research and Systems Medicine, ”Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Eskil Elmér
Mitochondrial Medicine, Department of Clinical Sciences, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden
Octavian Marius Crețu
Department IX Surgery—Surgical Semiotics I, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania
Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first–line lipid–lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM– and statin–induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell–permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.
