Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation
Autor: | Sudhi Tyagi, Amberly Anger, Jingli Wang, Kathryn Repp, Michael E. Widlansky, Venkata K. Puppala, Mamatha Kakarla, Rong Ying |
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Rok vydání: | 2019 |
Předmět: |
Male
lcsh:Diseases of the circulatory (Cardiovascular) system Brachial Artery Endocrinology Diabetes and Metabolism Vasodilation Pilot Projects Type 2 diabetes 030204 cardiovascular system & hematology Mitochondrion 0302 clinical medicine Leukocytes Uncoupling Protein 2 Prohibitin Brachial artery Inner mitochondrial membrane Original Investigation chemistry.chemical_classification Membrane Potential Mitochondrial 0303 health sciences Middle Aged Mitochondria medicine.anatomical_structure Female Mitochondrial membrane potential Cardiology and Cardiovascular Medicine Adult UCP2 medicine.medical_specialty Endothelium PHB 03 medical and health sciences Internal medicine medicine.artery Prohibitins medicine Humans 030304 developmental biology Aged Reactive oxygen species business.industry medicine.disease Repressor Proteins Endocrinology chemistry Diabetes Mellitus Type 2 lcsh:RC666-701 Case-Control Studies business Biomarkers |
Zdroj: | Cardiovascular Diabetology Cardiovascular Diabetology, Vol 18, Iss 1, Pp 1-11 (2019) |
ISSN: | 1475-2840 |
Popis: | Background Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. Methods Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. Results Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = − 0.35, P = 0.03). Conclusion Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation. |
Databáze: | OpenAIRE |
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