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Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy.
Circ Heart Fail. 2013 Sep 01; 6(5):1039-48.CH

Abstract

BACKGROUND

Cardiac hypertrophy is accompanied by significant alterations in energy metabolism. Whether these changes in energy metabolism precede and contribute to the development of heart failure in the hypertrophied heart is not clear.

METHODS AND RESULTS

Mice were subjected to cardiac hypertrophy secondary to pressure-overload as a result of an abdominal aortic constriction (AAC). The rates of energy substrate metabolism were assessed in isolated working hearts obtained 1, 2, and 3 weeks after AAC. Mice subjected to AAC demonstrated a progressive development of cardiac hypertrophy. In vivo assessment of cardiac function (via echocardiography) demonstrated diastolic dysfunction by 2 weeks (20% increase in E/E'), and systolic dysfunction by 3 weeks (16% decrease in % ejection fraction). Marked cardiac insulin-resistance by 2 weeks post-AAC was evidenced by a significant decrease in insulin-stimulated rates of glycolysis and glucose oxidation, and plasma membrane translocation of glucose transporter 4. Overall ATP production rates were decreased at 2 and 3 weeks post-AAC (by 37% and 47%, respectively) because of a reduction in mitochondrial oxidation of glucose, lactate, and fatty acids that was not accompanied by an increase in myocardial glycolysis rates. Reduced mitochondrial complex V activity was evident at 3 weeks post-AAC, concomitant with a reduction in the ratio of phosphocreatine to ATP.

CONCLUSIONS

The development of cardiac insulin-resistance and decreased mitochondrial oxidative metabolism are early metabolic changes in the development of cardiac hypertrophy, which create an energy deficit that may contribute to the progression from hypertrophy to heart failure.

Authors+Show Affiliations

Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23861485

Citation

Zhang, Liyan, et al. "Cardiac Insulin-resistance and Decreased Mitochondrial Energy Production Precede the Development of Systolic Heart Failure After Pressure-overload Hypertrophy." Circulation. Heart Failure, vol. 6, no. 5, 2013, pp. 1039-48.
Zhang L, Jaswal JS, Ussher JR, et al. Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy. Circ Heart Fail. 2013;6(5):1039-48.
Zhang, L., Jaswal, J. S., Ussher, J. R., Sankaralingam, S., Wagg, C., Zaugg, M., & Lopaschuk, G. D. (2013). Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy. Circulation. Heart Failure, 6(5), 1039-48. https://doi.org/10.1161/CIRCHEARTFAILURE.112.000228
Zhang L, et al. Cardiac Insulin-resistance and Decreased Mitochondrial Energy Production Precede the Development of Systolic Heart Failure After Pressure-overload Hypertrophy. Circ Heart Fail. 2013 Sep 1;6(5):1039-48. PubMed PMID: 23861485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy. AU - Zhang,Liyan, AU - Jaswal,Jagdip S, AU - Ussher,John R, AU - Sankaralingam,Sowndramalingam, AU - Wagg,Cory, AU - Zaugg,Michael, AU - Lopaschuk,Gary D, Y1 - 2013/07/16/ PY - 2013/7/18/entrez PY - 2013/7/19/pubmed PY - 2013/11/19/medline KW - abdominal aortic constriction KW - cardiac insulin-resistance KW - cardiomegaly KW - electron transport chain KW - energy metabolism KW - myocardial lipid accumulation SP - 1039 EP - 48 JF - Circulation. Heart failure JO - Circ Heart Fail VL - 6 IS - 5 N2 - BACKGROUND: Cardiac hypertrophy is accompanied by significant alterations in energy metabolism. Whether these changes in energy metabolism precede and contribute to the development of heart failure in the hypertrophied heart is not clear. METHODS AND RESULTS: Mice were subjected to cardiac hypertrophy secondary to pressure-overload as a result of an abdominal aortic constriction (AAC). The rates of energy substrate metabolism were assessed in isolated working hearts obtained 1, 2, and 3 weeks after AAC. Mice subjected to AAC demonstrated a progressive development of cardiac hypertrophy. In vivo assessment of cardiac function (via echocardiography) demonstrated diastolic dysfunction by 2 weeks (20% increase in E/E'), and systolic dysfunction by 3 weeks (16% decrease in % ejection fraction). Marked cardiac insulin-resistance by 2 weeks post-AAC was evidenced by a significant decrease in insulin-stimulated rates of glycolysis and glucose oxidation, and plasma membrane translocation of glucose transporter 4. Overall ATP production rates were decreased at 2 and 3 weeks post-AAC (by 37% and 47%, respectively) because of a reduction in mitochondrial oxidation of glucose, lactate, and fatty acids that was not accompanied by an increase in myocardial glycolysis rates. Reduced mitochondrial complex V activity was evident at 3 weeks post-AAC, concomitant with a reduction in the ratio of phosphocreatine to ATP. CONCLUSIONS: The development of cardiac insulin-resistance and decreased mitochondrial oxidative metabolism are early metabolic changes in the development of cardiac hypertrophy, which create an energy deficit that may contribute to the progression from hypertrophy to heart failure. SN - 1941-3297 UR - https://www.unboundmedicine.com/medline/citation/23861485/Cardiac_insulin_resistance_and_decreased_mitochondrial_energy_production_precede_the_development_of_systolic_heart_failure_after_pressure_overload_hypertrophy_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.112.000228?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -