Specific Up‐Regulation of Mitochondrial F₀F₁‐ATPase Activity after Short Episodes of Atrial Fibrillation in Sheep

Abstract

Specific activation of F0F1-ATPase activity is an early molecular consequence of sustained AF in sheep.

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation

“…In addition, it has been proposed that complex I plays an essential role in the assembly of respirasomes that bring together ETC subunits, providing structural interdependence to the individual OXPHOS complexes important in channeling electron flow, controlling superoxide production (13,38), and sensitivity of mitochondria toward mitochondrial permeability transition pore opening (28). Alterations in expression of genes and protein subunits of complex I lead to disassembly, instability of the complex, and an increase in reactive oxygen species (ROS) production, thus resulting in cardiac diseases, cardiomyopathy (7,18), and heart failure (28). The BN-PAGE data indicate no difference in mobility of the complexes, suggesting that the structure of the complexes is not altered and a selective reduction in complex I and II activity might be due to other alterations.…”

Energetic metabolism during acute stretch-related atrial fibrillation

“…Besides, direct and indirect evidence suggest that the activity of these two pumps might have been modified in our model. First, Barbey et al (12) have shown an increased activity of F 0 F 1 -ATPase but in absence of any change in Na,K-ATPase activity (7). On the other hand, the work by Songu-Mize et al (33) has shown increased Na pump activity by short term cyclic stretch in aortic smooth muscle cells.…”

“…While ionic remodeling (3)(4)(5) as well as changes in cellular and structural architecture (6) have been described, increasing evidence for a role of perturbations in energetic metabolism exists. In fact, various studies have shown modifications in energetic metabolism in both animal models (7)(8)(9)(10)(11) and humans (12)(13)(14) and after both chronic or short episodes of AF (9,10,(12)(13)(14). However, a variety of changes have been observed.…”

“…This substrate is of particular interest because atrial stretch is commonly associated with AF and has been demonstrated to play a critical role in the initiation and maintenance of this arrhythmia (15)(16)(17). Previously, some changes in atrial myocardial energetic status after the onset of fibrillation have been described in models with physiological elevation of intra-atrial pressure (7,8,11). Nevertheless, an evaluation of the energetic status in an AF model with a controlled high level of intra-atrial pressure and stretch has not been investigated.…”

“…However, a variety of changes have been observed. Several works describe an increased demand in energy (7)(8)(9)11) while others have suggested impaired energy production or consumption (10,(12)(13)(14). In order to clarify the atrial energetic status during AF, we investigated the consequences of acute atrial stretch on atrial myocytes energetic metabolism.…”