Author + information
- Jaehoon Chung,
- Euy-Myeong Jeong,
- Yeongju Go,
- Scott Gladstein,
- Afshin Farzaneh-Far,
- E. Douglas Lewandowski and
- Samuel Dudley
Heart failure with preserved ejection fraction (HFpEF) accounts for half the cases of HF with similar mortality to heart failure with reduced ejection fraction. Although the mechanism is unknown, high prevalence of obesity and diabetes has been associated with HFpEF. The aim of this study was to assess the effect of mitochondria-targeted antioxidant on diabetes-induced diastolic dysfunction.
C57BL/6J mice were fed either 60 kcal% fat diet (HFD) or 10 kcal% diet (control) for 8 weeks with or without daily intra-peritoneal Mito-TEMPO administration from week 4 to 8. Each group underwent ultra-high field tagged cardiac magnetic resonance imaging (CMR) and glucose tolerance testing prior to heart tissue harvest.
HFD mice developed obesity and diabetes evidenced by impaired glucose tolerance compared with the control (495 ± 45 mg/dL vs. 236 ± 30 at 60 min after glucose challenge, p<0.05). CMR tagging detected significantly reduced diastolic strain rate in the HFD mice compared with the control (5.0 ± 0.3 vs. 7.4 ± 0.5, p<0.05), indicating significant diastolic dysfunction in the HFD mice. Nevertheless, left ventricular ejection fraction was comparable between the two groups (66.4 ± 1.4 vs. 66.7 ± 1.2, p>0.05). This diabetes-induced diastolic dysfunction was correlated with significant mitochondria reactive oxygen species by flow cytometry, and the resultant oxidative damage to myofibrillar proteins by western blotting. Mito-TEMPO treatment attenuated obesity (27.5 ± 0.9 g vs. 33 ± 0.6 g, p<0.05) and significantly improved glucose tolerance (306 ± 36 mg/dL vs. 495 ± 45 mg/dL at 60 min after glucose challenge, p<0.05), compared with the HFD mice. CMR tagging showed mito-TEMPO treatment prevented diastolic dysfunction in the HFD mice as evidenced by comparable diastolic strain rate (6.5 ± 0.7 1/s vs. 7.4 ± 0.5 1/s. p>0.05) to the control.
Mitochondria-targeted antioxidant treatment attenuates obesity, glucose tolerance and diastolic dysfunction, suggesting cardiac oxidative stress may mediate HFpEF.
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Mechanisms of Metabolic Cardiomyopathy
Abstract Category: 16. Heart Failure: Basic
Presentation Number: 1135-292
- 2013 American College of Cardiology Foundation