CoQ10 enhances PGC1α and increases expression of mitochondrial antioxidant proteins in chronically ischemic swine myocardium

Abstract

BackgroundExpression 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 PGC1α signaling.Methods12 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 PGC1α (Western blots) and mitochondrial proteins (Tandem Mass Tag) were determined.ResultsMitochondrial and nuclear membranes were isolated from the LAD region. Nuclear-bound PGC1α 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.ConclusionsFour weeks of dietary CoQ10 in HM pigs enhances active, nuclear-bound PGC1α and increases the expression of ETC proteins within mitochondria of HM tissue.

Targetable Pathways for Alleviating Mitochondrial Dysfunction in Neurodegeneration of Metabolic and Non-Metabolic Diseases

“…In human neuroblastoma (SH-SY5Y) cells pre-treated with water-soluble CoQ 10 following H 2 O 2 treatment, a significant reduction in mitochondrial ROS generation, preserved ΔΨm, increased mitochondrial ATP production, and the prevention of mitochondrial membrane collapse were observed in comparison with the control mitochondria. This suggests that CoQ 10 can act as a potent antioxidant at the mitochondrial level, as CoQ 10 has been demonstrated to stabilise the mitochondrial membrane and increase mitochondrial numbers as a consequence of H 2 O 2 -induced OS, which may be due to the ability of CoQ 10 to increase PGC1α signalling [ 142 , 145 , 146 ]. Studies with senescence-accelerated mouse (SAM) models have revealed that a diet supplemented with CoQ 10 can induce pathways involving SIRT1, SIRT3, and PGC1α, preventing mitochondrial deterioration by increasing OS resistance [ 143 ].…”

An Adjuvant Stem Cell Patch with Coronary Artery Bypass Graft Surgery Improves Diastolic Recovery in Porcine Hibernating Myocardium

“…In a previous study, we observed no improvement in systolic functional recovery following adjunctive therapies such as CoQ10 [ 35 ]. When using an adjunctive MSC patch, however, we saw an improvement in systolic function without a significant increase in regional blood flow.…”

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“…Additionally, an increased efficiency of mitochondrial respiration (adenosine diphosphate/oxygen ratio) was observed ( p < 0.12) [ 12 ]. This improvement in mitochondrial efficiency has also been demonstrated in a swine model of chronic myocardial ischemia, wherein CoQ10 supplementation (400 mg/day) for 4 weeks enhanced nuclear-bound PGC1-α, indicating the activation of mitochondrial biogenesis, and increased the expression of antioxidant proteins within the mitochondria [ 60 ].…”