Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes
Open accessAbstract
There is compelling evidence to indicate an important role for increased local renin-angiotensin system activity in the pathogenesis of cardiac hypertrophy and heart failure. Resveratrol is a natural polyphenol that activates SIRT1, a novel cardioprotective and longevity factor having NAD(+)-dependent histone deacetylase activity. We tested the hypothesis whether resveratrol could prevent from angiotensin II (Ang II)-induced cardiovascular damage. Four-week-old double transgenic rats harboring human renin and human angiotensinogen genes (dTGR) were treated for 4 weeks either with SIRT1 activator resveratrol or SIRT1 inhibitor nicotinamide. Untreated dTGR and their normotensive Sprague-Dawley control rats (SD) received vehicle. Untreated dTGR developed severe hypertension as well as cardiac hypertrophy, and showed pronounced cardiovascular mortality compared with normotensive SD rats. Resveratrol slightly but significantly decreased blood pressure, ameliorated cardiac hypertrophy and prevented completely Ang II-induced mortality, whereas nicotinamide increased blood pressure without significantly influencing cardiac hypertrophy or survival. Resveratrol decreased cardiac ANP mRNA expression and induced cardiac mRNA expressions of mitochondrial biogenesis markers peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), mitochondrial transcription factor (Tfam), nuclear respiratory factor 1 (NRF-1) and cytochrome c oxidase subunit 4 (cox4). Resveratrol dose-dependently increased SIRT1 activity in vitro. Our findings suggest that the beneficial effects of SIRT1 activator resveratrol on Ang II-induced cardiac remodeling are mediated by blood pressure-dependent pathways and are linked to increased mitochondrial biogenesis.
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Resveratrol-dependent activation of SIRT1 triggers mitochondrial biogenesis in vitro and in transgenic rats by inducing mRNA expression of mitochondrial biogenesis markers such as PGC1α.
“Moreover, resveratrol-dependent activation of SIRT1 has also been shown to trigger mitochondrial biogenesis both in vitro and in transgenic rats with human genes for renin and angiotensinogen by inducing mRNA expression of mitochondrial biogenesis markers, such as PGC1α229.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [229]
Cites
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · see citing works
Recent progress in the biology and physiology of sirtuins
Finkel, T., Deng, C., & Mostoslavsky, R. (2009) · Nature · doi:10.1038/nature08197 · Cited by 1,484 · see citing works
Sirt1 Regulates Aging and Resistance to Oxidative Stress in the Heart
Alcendor, R. R., Gao, S., Zhai, P., Zablocki, D., Holle, E., Yu, X., Tian, B., Wagner, T., Vatner, S. F., & Sadoshima, J. (2007) · Circulation Research · doi:10.1161/01.res.0000267723.65696.4a · Cited by 1,147 · see citing works
Mechanism of Human SIRT1 Activation by Resveratrol
Borra, M. T., Smith, B. C., & Denu, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501250200 · Cited by 1,065 · see citing works
Calorie 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 · see citing works
Substrate-specific activation of sirtuins by resveratrol
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500655200 · Cited by 745 · see citing works
Doughan, A. K., Harrison, D. G., & Dikalov, S. I. (2008) · Circulation Research · doi:10.1161/circresaha.107.162800 · Cited by 710 · see citing works
Redox signaling in hypertension
Paravicini, T. M., & Touyz, R. M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.05.001 · Cited by 575 · see citing works
Resveratrol induces mitochondrial biogenesis in endothelial cells
Csiszár, A., Labinskyy, N., Pinto, J. T., Ballabh, P., Zhang, H., Losonczy, G., Pearson, K. J., de Cabo, R., Pacher, P., Zhang, C., et al. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00368.2009 · Cited by 450 · see citing works
SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
Boily, G., Seifert, E. L., Bevilacqua, L., He, X. H., Sabourin, G., Estey, C., Moffat, C., Crawford, S., Saliba, S., Jardine, K., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001759 · Cited by 444 · see citing works
Mitochondrial biogenesis and healthy aging
López-Lluch, G., Irusta, P. M., Navas, P., & de Cabo, R. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.014 · Cited by 364 · see citing works
Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats.
Rapp, J. P., & Dene, H. (1985) · Hypertension · doi:10.1161/01.hyp.7.3.340 · Cited by 308 · see citing works
Rajamohan, S. B., Pillai, V. B., Gupta, M., Sundaresan, N. R., Birukov, K. G., Samant, S. A., Hottiger, M. O., & Gupta, M. P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00121-09 · Cited by 303 · see citing works
Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage
Müller, D. N., Shagdarsuren, E., Park, J.-K., Dechend, R., Mervaala, E. M. A., Hampich, F., Fiebeler, A., Ju, X., Finckenberg, P., Theuer, J., et al. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64445-8 · Cited by 278 · see citing works
Self-citationMitochondrial biogenesis in exercise and in ageing☆
Viña, J., Gómez‐Cabrera, M. C., Borrás, C., Froio, T., Sanchis‐Gomar, F., Martinez-Bello, V. E., & Pallardó, F. V. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.06.006 · Cited by 251 · see citing works
Angiotensin II and vascular inflammation.
Cheng, Z. J., Vapaatalo, H., & Mervaala, E. M. A. (2005) · PubMed · Cited by 237 · see citing works
Self-citationGanten, D., Wagner, J., Zeh, K., et al. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7806 · Cited by 236 · see citing works
Miyazaki, R., Ichiki, T., Hashimoto, T., Inanaga, K., Imayama, I., Sadoshima, J., & Sunagawa, K. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.166991 · Cited by 214 · see citing works
Fiebeler, A., Schmidt, F. H., Müller, D. N., Park, J.-K., Dechend, R., Bieringer, M., Shagdarsuren, E., Breu, V., Haller, H. G., & Luft, F. C. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.787 · Cited by 211 · see citing works
Shin, S. M., Cho, I. J., & Kim, S. G. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.058479 · Cited by 195 · see citing works
Necdin Regulates p53 Acetylation via Sirtuin1 to Modulate DNA Damage Response in Cortical Neurons
Hasegawa, K., & Yoshikawa, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3052-08.2008 · Cited by 162 · see citing works
Westhoff, J. H., Hilgers, K. F., Steinbach, M. P., Hartner, A., Klanke, B., Amann, K., & Melk, A. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.099432 · Cited by 152 · see citing works
NAD+, Sirtuins, and Cardiovascular Disease
Borradaile, N. M., & Pickering, J. G. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209787185742 · Cited by 140 · see citing works
Alcaín, F. J., & Villalba, J. M. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770902762893 · Cited by 137 · see citing works
High Human Renin Hypertension in Transgenic Rats
Bohlender, J. M., Fukamizu, A., Lippoldt, A., Nomura, T., Dietz, R., Ménard, J., Murakami, K., Luft, F. C., & Ganten, D. (1997) · Hypertension · doi:10.1161/01.hyp.29.1.428 · Cited by 130 · see citing works
Chlopčíková, Š., Psotová, J., & Miketová, P. (2001) · Biomedical Papers · doi:10.5507/bp.2001.011 · Cited by 115 · see citing works
Pillai, J. B., Gupta, M., Rajamohan, S. B., Lang, R. M., Raman, J., & Gupta, M. P. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01124.2005 · Cited by 110 · see citing works
Structural, functional, and molecular characterization of the SHHF model of heart failure
Heyen, J. R. R., Blasi, E., Nikula, K. J., Rocha, R., Daust, H. A., Frierdich, G. E., Vleet, J. F. V., Ciechi, P. D., McMahon, E. G., & Rudolph, A. E. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00305.2002 · Cited by 106 · see citing works
Müller, D. N., Mervaala, E. M. A., Dechend, R., et al. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64523-3 · Cited by 96 · see citing works
Self-citationNicotinamide Reverses Neurological and Neurovascular Deficits in Streptozotocin Diabetic Rats
Stevens, M. J., Li, F. R., Drel, V. R., Abatan, O. I., Kim, H., Burnett, D., Larkin, D. D., & Obrosova, I. G. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.109702 · Cited by 88 · see citing works
Louhelainen, M., Vahtola, E., Kaheinen, P., et al. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707157 · Cited by 79 · see citing works
Self-citationVahtola, E., Louhelainen, M., Merasto, S., Martonen, E., Penttinen, S., Aahos, I., Kytö, V., Virtanen, I., & Mervaala, E. M. A. (2008) · Journal of Hypertension · doi:10.1097/hjh.0b013e3282f293c8 · Cited by 70 · see citing works
Self-citationHossain, M. B., Ji, P., Anish, R., Jacobson, R. H., & Takada, S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807198200 · Cited by 57 · see citing works
Cardiac gene expression profile in rats with terminal heart failure and cachexia
Wellner, M., Dechend, R., Park, J.-K., et al. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00165.2004 · Cited by 57 · see citing works
Immunology in Hypertension, Preeclampsia, and Target-Organ Damage
Verlohren, S., Müller, D. N., Luft, F. C., & Dechend, R. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.120253 · Cited by 55 · see citing works
The anti-aging, metabolism potential of SIRT1.
Ghosh, H. S. (2008) · PubMed · Cited by 49 · see citing works
Sirt1 is involved in energy metabolism: The role of chronic ethanol feeding and resveratrol
Oliva, J., French, B. A., Li, J., Bardag‐Gorce, F., Fu, P. C., & French, S. W. (2008) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2008.08.002 · Cited by 49 · see citing works
Angiotensin II promotes poly(ADP-ribosyl)ation of c-Jun/c-Fos in cardiac fibroblasts
Huang, D. Y., Wang, Y., Yang, C., Liao, Y., & Huang, K. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.10.019 · Cited by 46 · see citing works
Yamamoto, E., Kataoka, K., Yamashita, T., Tokutomi, Y., Dong, Y., Matsuba, S., Ogawa, H., & Kim‐Mitsuyama, S. (2007) · Hypertension · doi:10.1161/hypertensionaha.107.095315 · Cited by 44 · see citing works
Metabolomics in Angiotensin II-Induced Cardiac Hypertrophy
Mervaala, E. M. A., Biala, A. K., Merasto, S., Lempiäinen, J., Mattila, I. M., Martonen, E., Eriksson, O., Louhelainen, M., Finckenberg, P., Kaheinen, P., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.145490 · Cited by 43 · see citing works
Self-citationMolecular analysis of the Ink4a/Rb1–Arf/Tp53 pathways in radon-induced rat lung tumors
Bastide, K., Guilly, M., Bernaudin, J., Joubert, C., Lectard, B., Levalois, C., Malfoy, B., & Chevillard, S. (2008) · Lung Cancer · doi:10.1016/j.lungcan.2008.06.007 · Cited by 38 · see citing works
Entacapone protects from angiotensin II-induced inflammation and renal injury
Helkamaa, T., Finckenberg, P., Louhelainen, M., Merasto, S., Rauhala, P. V., Lapatto, R., Cheng, Z. J., Reenilä, I., Männistö, P. T., Müller, D. N., et al. (2003) · Journal of Hypertension · doi:10.1097/00004872-200312000-00025 · Cited by 24 · see citing works
Self-citationGenetic Characterization of the ‘New’ Harlan Sprague Dawley Dahl Salt-Sensitive Rats
Walder, R. Y., Morgan, D. A., Haynes, W. G., et al. (1996) · Hypertension · doi:10.1161/01.hyp.27.3.546 · Cited by 19 · see citing works
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- Authors
- Biala, A., Tauriainen, E., Siltanen, A., Shi, J., Merasto, S., Louhelainen, M., Martonen, E., Finckenberg, P., Muller, D. N., & Mervaala, E.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Mervaala, Eero
- ORCID
- Shi, Jin
- Venue
- Blood Pressure
- Publisher
- Informa UK Limited
- Published
- 2010-01
- Volume
- 19
- Issue
- 3
- Pages
- 196-205
- ISSN
- 0803-7051 (ISSN-L)
- 1651-1999
- OpenAlex
- W2158902191
- Cited by
- 97
- References
- 44
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 9
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood Pressure (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Foundation for Cardiovascular Research
- Sigrid Juséliuksen Säätiö
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- resveratrol, SIRT1, angiotensin II, cardiac remodeling, cardiac hypertrophy, mitochondrial biogenesis, renin-angiotensin system, nicotinamide, PGC-1α, TFAM, NRF1, atrial natriuretic peptide, hypertension, cardioprotection
- MeSH terms
- Resveratrol, Angiotensin II, Angiotensinogen, Animals, Blood Pressure, Genes, Heart, Cardiomegaly, Humans, Hypertension, Male, Mitochondria, Renin, Renin-Angiotensin System, Stilbenes, Rats, Sprague-Dawley, Rats, Rats, Transgenic
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