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CoQ10 enhances PGC1? and increases expression of mitochondrial antioxidant proteins in chronically ischemic swine myocardium.

ABSTRACT: Background:Expression of mitochondrial proteins is reduced within hibernating myocardium (HM). It is unclear whether dietary supplementation with CoQ10 can increase expression of mitochondrial electron transport chain (ETC) and antioxidant proteins within this tissue. In a swine model of HM, we tested whether dietary administration of CoQ10 for four weeks enhances the expression of ETC and antioxidant proteins within the mitochondria via increased PGC1? signaling. Methods:12 swine were instrumented with a fixed constrictor around the LAD artery to induce gradual stenosis. At three months, transthoracic ECHO was performed to confirm the presence of a wall motion abnormality in the anterior wall. Animals were then randomly assigned to receive daily dietary supplements of either CoQ10 (10?mg/kg/day) or placebo for four weeks. At this time, animals underwent a final ECHO and terminal procedure. Expression of nuclear-bound PGC1? (Western blots) and mitochondrial proteins (Tandem Mass Tag) were determined. Results:Mitochondrial and nuclear membranes were isolated from the LAD region. Nuclear-bound PGC1? levels were?>?200-fold higher with administration of four weeks of CoQ10 treatment (p?=?0.016). Expression of ETC proteins was increased in those animals that received CoQ10. Compared with mitochondria in the LAD region from placebo-treated pigs, CoQ10-treated pigs had higher levels of Complex I (p?=?0.03), Complex IV (p?=?0.04) and Complex V (p?=?0.028) peptides. Conclusions:Four weeks of dietary CoQ10 in HM pigs enhances active, nuclear-bound PGC1? and increases the expression of ETC proteins within mitochondria of HM tissue.

SUBMITTER: Hocum Stone L

PROVIDER: S-EPMC6937679 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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CoQ<sub>10</sub> enhances PGC1α and increases expression of mitochondrial antioxidant proteins in chronically ischemic swine myocardium.

Hocum Stone Laura L Chappuis Erin E Wright Christin C Kelly Rosemary F RF McFalls Edward O EO

Nutrition & metabolism 20191230

<h4>Background</h4>Expression of mitochondrial proteins is reduced within hibernating myocardium (HM). It is unclear whether dietary supplementation with CoQ<sub>10</sub> can increase expression of mitochondrial electron transport chain (ETC) and antioxidant proteins within this tissue. In a swine model of HM, we tested whether dietary administration of CoQ<sub>10</sub> for four weeks enhances the expression of ETC and antioxidant proteins within the mitochondria via increased PGC1α signaling.<h ...[more]

PMID: 31892934

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Project description:BackgroundOxidative stress is highly prevalent in patients with end-stage renal disease and is linked to excess cardiovascular risk. Identifying therapies that reduce oxidative stress has the potential to improve cardiovascular outcomes in patients undergoing maintenance dialysis.Study designPlacebo-controlled, 3-arm, double-blind, randomized, clinical trial.Setting & participants65 patients undergoing thrice-weekly maintenance hemodialysis.InterventionPatients were randomly assigned in a 1:1:1 ratio to receive once-daily coenzyme Q10 (CoQ10; 600 or 1,200mg) or matching placebo for 4 months.OutcomesThe primary outcome was plasma oxidative stress, defined as plasma concentration of F2-isoprotanes. Secondary outcomes included levels of plasma isofurans, levels of cardiac biomarkers, predialysis blood pressure, and safety/tolerability.MeasurementsF2-isoprostanes and isofurans were measured as plasma markers of oxidative stress, and N-terminal pro-brain natriuretic peptide and troponin T were measured as cardiac biomarkers at baseline and 1, 2, and 4 months.ResultsOf 80 randomly assigned patients, 15 were excluded due to not completing at least 1 postbaseline study visit and 65 were included in the primary intention-to-treat analysis. No treatment-related major adverse events occurred. Daily treatment with 1,200mg, but not 600mg, of CoQ10 significantly reduced plasma F2-isoprostanes concentrations at 4 months compared to placebo (adjusted mean changes of -10.7 [95% CI, -7.1 to -14.3] pg/mL [P<0.001] and -8.3 [95% CI, -5.5 to -11.0] pg/mL [P=0.1], respectively). There were no significant effects of CoQ10 treatment on levels of plasma isofurans, cardiac biomarkers, or predialysis blood pressures.LimitationsStudy not powered to detect small treatment effects; difference in baseline characteristics among randomized groups.ConclusionsIn patients undergoing maintenance hemodialysis, daily supplementation with 1,200mg of CoQ10 is safe and results in a reduction in plasma concentrations of F2-isoprostanes, a marker of oxidative stress. Future studies are needed to determine whether CoQ10 supplementation improves clinical outcomes for patients undergoing maintenance hemodialysis.

Dataset Information

CoQ10 enhances PGC1? and increases expression of mitochondrial antioxidant proteins in chronically ischemic swine myocardium.

Publications

CoQ<sub>10</sub> enhances PGC1α and increases expression of mitochondrial antioxidant proteins in chronically ischemic swine myocardium.

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