The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients.
It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA-IR, HbA1c, triglycerides, hs-CRP and lower HDL-c with respect to controls. Mitochondrial ROS production was enhanced in T2D patients and decreased by MitoQ. The antioxidant also increased GPX-1 levels and PMN rolling velocity and decreased PMN rolling flux and PMN adhesion in T2D patients. NFκB-p65 and TNFα were augmented in T2D and were both reduced by MitoQ treatment. Our findings support that the antioxidant MitoQ has an anti-inflammatory and antioxidant action in the leukocytes of T2D patients by decreasing ROS production, leukocyte-endothelium interactions and TNFα through the action of NFκB. These data suggest that mitochondria-targeted antioxidants such as MitoQ should be investigated as a novel means of preventing cardiovascular events in T2D patients.
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
Irene
I
Escribano-Lopez
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
Noelia
N
Diaz-Morales
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
Susana
S
Rovira-Llopis
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
Arantxa Martinez
AM
de Marañon
CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.
Samuel
S
Orden
CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.
Angeles
A
Alvarez
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
Celia
C
Bañuls
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.
Milagros
M
Rocha
MRC Mitochondrial Biology Unit, Cambridge, United Kingdom.
Michael P
MP
Murphy
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain.
Antonio
A
Hernandez-Mijares
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain. Electronic address: victor.victor@uv.es.
Victor M
VM
Victor
D000368:Aged; D000886:Anthropometry; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000094765:Glutathione Peroxidase GPX1
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D009943:Organophosphorus Compounds; C498143:RELA protein, human; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014451:Ubiquinone; C429014:mitoquinone; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
Endothelium; Inflammation; Leukocytes; MitoQ; Oxidative stress; Type 2 diabetes