Mitochondrial fusion proteins in revascularized hibernating hearts

Holley, Christopher T.; Long, Eric K.; Butterick, Tammy A.; Duffy, Cayla M.; Lindsey, Megan E.; Stone, Laura Hocum; McFalls, Edward O.; Kelly, Rosemary F.

doi:10.1016/j.jss.2014.12.052

Cited by 12 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fusion protein (OPA-1, mitofusins 1 and 2) expression is necessary to re-establish normal mitochondrial energetics and function in the adult heart 19 . We have also demonstrated that PGC1α, a driver of mitochondrial biogenesis, is significantly downregulated in HM and is not restored following CABG 17 . Using transmission electron microscopy, we have observed in our HM model that mitochondria appear smaller and more variable in size despite CABG, which could be explained by the dysregulation of mitochondrial fusion, fission, and autophagy.…”

Section: Discussionmentioning

confidence: 73%

“…Using transmission electron microscopy, we have observed in our HM model that mitochondria appear smaller and more variable in size despite CABG, which could be explained by the dysregulation of mitochondrial fusion, fission, and autophagy. This mitochondrial morphology does not normalize following CABG 17 . These observations identify the mitochondrial basis of HM, but clinical studies and animal models of HM are limited in their ability to allow the direct study of mitochondrial respiration.…”

Section: Discussionmentioning

confidence: 85%

“…We have previously demonstrated that inadequate mitochondrial bioenergetic capacity is present in HM pre- and post-CABG, as manifested by reduced expression of ETC proteins 17 . These observations suggest the process of mitochondrial dynamism is incomplete with CABG alone and that recovery of the mitochondrial proteome remains inadequate, despite evidence that cardiac tissue is no longer ischemic following CABG, as indicated by full restoration of regional blood flow in the HM region 8,18 . Fusion protein (OPA-1, mitofusins 1 and 2) expression is necessary to re-establish normal mitochondrial energetics and function in the adult heart 19 .…”

Section: Discussionmentioning

confidence: 99%

“…A critical balance between these variables is necessary to preserve mitochondrial energetics and contractile function in the ischemic heart 17 . We have previously demonstrated that inadequate mitochondrial bioenergetic capacity is present in HM pre- and post-CABG, as manifested by reduced expression of ETC proteins 17 . These observations suggest the process of mitochondrial dynamism is incomplete with CABG alone and that recovery of the mitochondrial proteome remains inadequate, despite evidence that cardiac tissue is no longer ischemic following CABG, as indicated by full restoration of regional blood flow in the HM region 8,18 .…”

Section: Discussionmentioning

confidence: 99%

“…These indicators of mitochondrial dysfunction are not restored to normal following restoration of blood flow with CABG 9,10 . In addition, electron micrographs of this tissue show the mitochondria are small, segmented, and disorganized 10 . These data suggest the persistent mitochondrial dysfunction in HM despite revascularization inhibits full functional recovery.…”

Section: Introductionmentioning

confidence: 98%

See 4 more Smart Citations

Mitochondrial Respiratory Capacity is Restored in Hibernating Cardiomyocytes Following Co-Culture with Mesenchymal Stem Cells

et al. 2019

Self Cite

View full text Add to dashboard Cite

Hibernating myocardium is a subset of ischemic cardiac disease characterized by viable but dysfunctional tissue. Standard treatment for hibernating myocardium is coronary artery bypass graft, which reduces arrhythmias and improves survival but does not fully restore function, presenting a gap in currently available treatments. Large animal studies of hibernating myocardium have identified impaired mitochondrial dynamics as a root cause of persistent cardiac dysfunction despite surgical revascularization. This study presents a novel in vitro model of hibernating myocardium cardiomyocytes to study active mitochondrial respiration in hibernating myocardium cells, and to test the paracrine effect of mesenchymal stem cells on impaired mitochondrial function. Exposure of cardiomyocytes to hypoxic conditions of 1% oxygen for 24 hours resulted in a phenotype consistent with hibernating myocardium cardiac tissue, including decreased respiratory capacity under high work states, decreased expression of mitochondrial proteins, and preserved cellular viability. Co-culture of hibernating myocardium cardiomyocytes with mesenchymal stem cells restored mitochondrial respiratory function, potentially via an increase in proliferator-activated receptor gamma coactivator 1-alpha-driven mitochondrial biogenesis. Co-culture treatment of hibernating myocardium cardiomyocytes with mesenchymal stem cells shows improvement in both mitochondrial function and ATP production, both of which are critical for effectively functioning cardiac tissue. These results suggest that mesenchymal stem cell therapy as an adjunct treatment to revascularization may address the current gap in treatment for hibernating myocardium patients.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 85%