Mitochondrial fusion proteins in revascularized hibernating hearts

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

来源：Journal of Surgical Research, 2015, 195(1): 29-36.

DOI：10.1016/j.jss.2014.12.052

• Hibernating myocardium
• Coronary artery bypass graft surgery
• Mitochondrial disease cardiomyopathy
• Animal model of cardiovascular disease
• Ischemic heart disease

Background: Hibernating myocardium is characterized by viable yet dysfunctional myocardium secondary to chronic ischemia, with studies demonstrating incomplete early recovery after coronary artery bypass graft (CABG). We tested whether mitochondrial fusion proteins, an indicator of mitochondrial biogenesis, are increased in hibernating myocardium post-CABG.
Methods: A constrictor was placed on the left anterior descending (LAD) artery of nine pigs. Four of these pigs additionally underwent CABG 12 wk later with a left internal mammary artery graft to the LAD distal to the constrictor. Five pigs had a constrictor placed but did not undergo CABG (Hib). Five pigs did not have a constrictor placed (control). Computerized tomography angiography was used to confirm stenosis at the site of constrictor placement and patency of left internal mammary artery grafts. Regional blood flows were determined at baseline and during 40 mu g/kg/min dobutamine infusion. Mitochondrial proteins were quantified by Western blot.
Results: Blood flow in the LAD region after CABG was lower than remote regions during dobutamine infusion (2.54 +/- 0.24 versus 3.46 +/- 0.33 mL/min/g; P < 0.05). Electron transport chain proteins were similar to 70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1 alpha nuclear-bound content was increased compared with Hib (9.02 +/- 0.48 versus 5.54 +/- 0.98 arbitrary units, respectively; P < 0.05), and expression of mitofusins-1 and 2 and optic atrophy-1 more than doubled.
Conclusions: PGC1a and mitochondrial fusion proteins are increased 4 wk post-CABG in hibernating hearts, indicating mitochondrial fusion has begun to occur and signaling early mitochondrial recovery. Future studies should address changes in maximal myocardial oxygen consumption relative to mitochondrial protein expression.

• 出版日期2015-5-1