TY - JOUR
T1 - Mitochondrial fusion proteins in revascularized hibernating hearts
AU - Holley, Christopher T.
AU - Long, Eric K.
AU - Butterick, Tammy A.
AU - Duffy, Cayla M.
AU - Lindsey, Megan E.
AU - Stone, Laura Hocum
AU - McFalls, Edward O.
AU - Kelly, Rosemary F.
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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 μg/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 ∼70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1α 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 PGC1α 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.
AB - 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 μg/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 ∼70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1α 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 PGC1α 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.
KW - Animal model of cardiovascular disease
KW - Coronary artery bypass graft surgery
KW - Hibernating myocardium
KW - Ischemic heart disease
KW - Mitochondrial disease cardiomyopathy
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U2 - 10.1016/j.jss.2014.12.052
DO - 10.1016/j.jss.2014.12.052
M3 - Article
C2 - 25655995
AN - SCOPUS:84926217892
SN - 0022-4804
VL - 195
SP - 29
EP - 36
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -