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Improvement of platelet respiration by cell-permeable succinate in diabetic patients treated with statins

Avram, Vlad Florian LU ; Bîna, Anca Mihaela ; Sima, Alexandra ; Aburel, Oana Maria ; Sturza, Adrian ; Burlacu, Ovidiu ; Timar, Romulus Zorin ; Muntean, Danina Mirela ; Elmér, Eskil LU orcid and Cret, Octavian Marius (2021) In Life 11(4).
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell-permeable succinate (NV118), Diabetes, High-resolution respirometry, Mitochondria, Platelets, Statins
in
Life
volume
11
issue
4
article number
288
publisher
MDPI AG
external identifiers
  • scopus:85103590860
  • pmid:33800630
ISSN
0024-3019
DOI
10.3390/life11040288
language
English
LU publication?
yes
id
616c3f9b-0dab-44c8-9a46-8b6f0d9af2c2
date added to LUP
2021-04-14 11:15:45
date last changed
2024-06-15 09:52:02
@article{616c3f9b-0dab-44c8-9a46-8b6f0d9af2c2,
  abstract     = {{<p>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.</p>}},
  author       = {{Avram, Vlad Florian and Bîna, Anca Mihaela and Sima, Alexandra and Aburel, Oana Maria and Sturza, Adrian and Burlacu, Ovidiu and Timar, Romulus Zorin and Muntean, Danina Mirela and Elmér, Eskil and Cret, Octavian Marius}},
  issn         = {{0024-3019}},
  keywords     = {{Cell-permeable succinate (NV118); Diabetes; High-resolution respirometry; Mitochondria; Platelets; Statins}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{Life}},
  title        = {{Improvement of platelet respiration by cell-permeable succinate in diabetic patients treated with statins}},
  url          = {{http://dx.doi.org/10.3390/life11040288}},
  doi          = {{10.3390/life11040288}},
  volume       = {{11}},
  year         = {{2021}},
}