The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Metformin Prevents Progression of Heart Failure in Dogs: Role of AMP-Activated Protein Kinase
Abstract
Background— Some studies have shown that metformin activates AMP-activated protein kinase (AMPK) and has a potent cardioprotective effect against ischemia/reperfusion injury. Because AMPK also is activated in animal models of heart failure, we investigated whether metformin decreases cardiomyocyte apoptosis and attenuates the progression of heart failure in dogs. Methods and Results— Treatment with metformin (10 μmol/L) protected cultured cardiomyocytes from cell death during exposure to H 2 O 2 (50 μmol/L) via AMPK activation, as shown by the MTT assay, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining, and flow cytometry. Continuous rapid ventricular pacing (230 bpm for 4 weeks) caused typical heart failure in dogs. Both left ventricular fractional shortening and left ventricular end-diastolic pressure were significantly improved in dogs treated with oral metformin at 100 mg · kg −1 · d −1 (n=8) (18.6±1.8% and 11.8±1.1 mm Hg, respectively) compared with dogs receiving vehicle (n=8) (9.6±0.7% and 22±0.9 mm Hg, respectively). Metformin also promoted phosphorylation of both AMPK and endothelial nitric oxide synthase, increased plasma nitric oxide levels, and improved insulin resistance. As a result of these effects, metformin decreased apoptosis and improved cardiac function in failing canine hearts. Interestingly, another AMPK activator (AICAR) had effects equivalent to those of metformin, suggesting the primary role of AMPK activation in reducing apoptosis and preventing heart failure. Conclusions— Metformin attenuated oxidative stress–induced cardiomyocyte apoptosis and prevented the progression of heart failure in dogs, along with activation of AMPK. Therefore, metformin may be a potential new therapy for heart failure.
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1 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M.-H., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 478
RetractedRole of AMP-Activated Protein Kinase in Mechanism of Metformin Action
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TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
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Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
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AMP‐activated protein kinase phosphorylation of endothelial NO synthase
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Tachycardia-Induced Cardiomyopathy: A Review of Animal Models and Clinical Studies
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Fatty Acid Oxidation Enzyme Gene Expression Is Downregulated in the Failing Heart
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Cited by
Cellular and molecular mechanisms of metformin: an overview
Viollet, B., Guigas, B., Garcia, N. S., Leclerc, J., Foretz, M., & Andreelli, F. (2012) · Clinical Science · doi:10.1042/cs20110386 · Cited by 1,720
Metformin: from mechanisms of action to therapies
Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501
Anti-inflammatory effects of metformin irrespective of diabetes status
Cameron, A. R., Morrison, V. L., Levin, D., Mohan, M., Forteath, C., Beall, C., McNeilly, A. D., Balfour, D. J. K., Savinko, T., Wong, A. K. F., et al. (2016) · Circulation Research · doi:10.1161/circresaha.116.308445 · Cited by 704
The Role of Autophagy in the Heart
Sciarretta, S., Maejima, Y., Zablocki, D., & Sadoshima, J. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121427 · Cited by 547
Bozkurt, B., Aguilar, D., Deswal, A., Dunbar, S. B., Francis, G. S., Horwich, T., Jessup, M., Kosiborod, M., Pritchett, A. M., Ramasubbu, K., et al. (2016) · Circulation · doi:10.1161/cir.0000000000000450 · Cited by 522
Metadata
- Authors
- Sasaki, H., Asanuma, H., Fujita, M., Takahama, H., Wakeno, M., Ito, S., Ogai, A., Asakura, M., Kim, J., Minamino, T., Takashima, S., Sanada, S., Sugimachi, M., Komamura, K., Mochizuki, N., & Kitakaze, M.
- Venue
- Circulation
- Published
- 2009-05-19
- Volume
- 119
- Issue
- 19
- Pages
- 2568-2577
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1998877815
- Cited by
- 289
- References
- 42
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- closed
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- Sasaki, H., Asanuma, H., Fujita, M., Takahama, H., Wakeno, M., Ito, S., Ogai, A., Asakura, M., Kim, J., Minamino, T., Takashima, S., Sanada, S., Sugimachi, M., Komamura, K., Mochizuki, N., & Kitakaze, M. (2009). Metformin Prevents Progression of Heart Failure in Dogs: Role of AMP-Activated Protein Kinase. Circulation. https://doi.org/10.1161/circulationaha.108.798561
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