The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance
Open accessAbstract
Objectives The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF) and to determine potential relationships with measures of exercise performance. Background Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF, is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism, however little is known about how these organelles are affected in HFpEF. Methods Vastus lateralis skeletal muscle citrate synthase activity, and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n=20) and healthy, age-matched controls (n=17). Results In HFpEF patients compared to age-matched healthy controls, mitochondrial content assessed by Porin expression was 46% lower (p-value= 0.01), citrate synthase activity was 29% lower (p= 0.01), and Mfn2 expression was 54% lower (p= <0.001). Expression of Porin was significantly positively correlated with both peak VO2 and 6 minute walk distance (r=0.48, p=0.003 and r=0.33, p=0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6 minute walk distance (r=0.40, p=0.02 and r=0.37, p=0.03 respectively). Conclusion These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and may contribute to their severe exercise intolerance.
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Cites
2013 ACCF/AHA Guideline for the Management of Heart Failure
Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T., Januzzi, J. L., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.019 · Cited by 12,536
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects
Larsen, S., Nielsen, J., Hansen, C. N., Nielsen, L. B., Wibrand, F., Stride, N., Schroder, H. D., Boushel, R., Helge, J. W., Dela, F., et al. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.230185 · Cited by 1,180 · cited 1×
“Further validation was provided by measurement of citrate synthase activity, a biomarker widely recognized as the most reliable indicator of skeletal muscle oxidative capacity and mitochondrial content (14).”
MethodKitzman, D. W. (2002) · JAMA · doi:10.1001/jama.288.17.2144 · Cited by 883
Self-citationCalorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790
The Interplay Between Mitochondrial Dynamics and Mitophagy
Twig, G., & Shirihai, O. S. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3779 · Cited by 778
Epidemiology and clinical course of heart failure with preserved ejection fraction
Lam, C. S. P., Donal, E., Kraigher-Krainer, E., & Vasan, R. S. (2011) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfq121 · Cited by 709
Sebastián, D., Hernández-Alvarez, M. I., Segalés, J., Sorianello, E., Muñoz, J. P., Sala, D., Waget, A., Liesa, M., Paz, J. C., Gopalacharyulu, P., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108220109 · Cited by 673
Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle
Bach, D., Naon, D., Pich, S., Soriano, F. X., Vega, N., Rieusset, J., Laville, M., Guillet, C., Boirie, Y., Wallberg-Henriksson, H., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2685 · Cited by 369 · cited 2×
“Although a previous study reported that Mfn2 messenger ribonucleic acid is decreased in the skeletal muscle of obese people (42), a more recent study has shown that protein content of Mfn2 is unaffected (43).”
BackgroundResultKitzman, D. W., Brubaker, P. H., Herrington, D. M., Morgan, T. M., Stewart, K. P., Hundley, W. G., Abdelhamed, A., & Haykowsky, M. J. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.04.033 · Cited by 369
Self-citation
Cited by
Heart Failure With Preserved Ejection Fraction In Perspective
Pfeffer, M. A., Shah, A. M., & Borlaug, B. A. (2019) · Circulation Research · doi:10.1161/circresaha.119.313572 · Cited by 837
Evaluation and management of heart failure with preserved ejection fraction
Borlaug, B. A. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0363-2 · Cited by 675
Exercise Intolerance in Patients With Heart Failure
Del Buono, M. G., Arena, R., Borlaug, B. A., Carbone, S., Canada, J. M., Kirkman, D. L., Garten, R., Rodriguez-Miguelez, P., Guazzi, M., Lavie, C. J., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.01.072 · Cited by 477
Borlaug, B. A., Jensen, M. D., Kitzman, D. W., Lam, C. S. P., Obokata, M., & Rider, O. J. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvac120 · Cited by 450
Self-citationHeart failure with preserved ejection fraction: from mechanisms to therapies
Lam, C. S. P., Voors, A. A., de Boer, R. A., Solomon, S. D., & van Veldhuisen, D. J. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy301 · Cited by 355
Metadata
- Authors
- Molina, A. J. A., Bharadwaj, M. S., Van Horn, C., Nicklas, B. J., Lyles, M. F., Eggebeen, J., Haykowsky, M. J., Brubaker, P. H., & Kitzman, D. W.
- Venue
- JACC: Heart Failure
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 4
- Issue
- 8
- Pages
- 636-645
- ISSN
- 2213-1779 (ISSN-L)
- OpenAlex
- W2364050795
- Cited by
- 207
- References
- 16
- FWCI
- 36.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Molina, A. J. A., Bharadwaj, M. S., Van Horn, C., Nicklas, B. J., Lyles, M. F., Eggebeen, J., Haykowsky, M. J., Brubaker, P. H., & Kitzman, D. W. (2016). Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance. JACC: Heart Failure. https://doi.org/10.1016/j.jchf.2016.03.011
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