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Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of apolipoprotein E-deficient mice
Abstract
Dietary restriction (DR) has been shown to inhibit almost all the age-related diseases, e.g. cardiomyopathy and cancers, in rodents. However, there is little information for the effect of DR on atherosclerosis. In the present study, we examined the effect of DR on the development of atherosclerosis in mice homozygous knockout for apolipoprotein E gene (ApoE(-/-)). The ApoE(-/-) mice were fed either ad libitum (AL) or 60% of the diet consumed by the mice fed AL. Atherosclerotic lesions in the proximal aorta of these mice were measured. Our results showed that ApoE(-/-) mice fed the calorie-restricted diet had smaller and relatively early stages of atherosclerotic lesions (e.g. foam cells and free lipids) when compared to ApoE(-/-) mice fed AL, who developed more advanced lesions (e.g. fibrous caps and acellular areas). In addition, ApoE(-/-) mice fed the calorie-restricted diet showed a significant decrease in the level of lipid hydroperoxides and the production of superoxide and hydrogen peroxide in the aorta as compared to ApoE(-/-) mice fed AL. These observations suggest that reduction of oxidative stress in the arterial wall may contribute to the anti-atherogenic effect of DR in ApoE(-/-) mice.
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“Apart from lifespan extension, caloric restriction also reduces the risk factors for major diseases including diabetes and cardiovascular disease in rodents (209, 210).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [209]
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“[71] have shown that CR (40% CR for 19 weeks) retards the progression of atherosclerotic lesion formation in apolipoprotein E knockout mice.”
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“…effect of DR on atherosclerosis, plaque deposition, hypertension, and other cardiovascular complications is exerted via the modulation of the activity of both SIRT1 and AMPK (48, 64, 106) whose activity reduces ROS generation (28, 35) and improves mitochondrial biogenesis and function (156).”
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Zinc finger E‐box binding homeobox 1 and atherosclerosis: New insights and therapeutic potential
Li, H., Zou, J., Yu, X., Ou, X., & Tang, C. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30177 · Cited by 20
Dieta Intermitente Atenua a Remodelação Cardíaca Causada pelo Exercício Físico
Basilio, P. G., de Oliveira, A. P. C., de Castro, A. C. F., de Carvalho, M. R., Zagatto, A. M., Martinez, P. F., Okoshi, M. P., Okoshi, K., Ota, G. E., dos Reis, F. A., et al. (2020) · Arquivos Brasileiros de Cardiologia · doi:10.36660/abc.20190349 · Cited by 17
Food with calorie restriction reduces the development of atherosclerosis in apoE-deficient mice
Yang, J. A., Zeng, P., Liu, L., Yu, M., Su, J., Yan, Y., Ma, J., Hu, W., Yang, X., Han, J., et al. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.01.109 · Cited by 17
Li, J., Niu, X.-L., & Madamanchi, N. R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806087200 · Cited by 15
The impacts of different dietary restriction regimens on aging and longevity: from yeast to humans
Ching, T., & Hsu, A. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01188-w · Cited by 17
Molecular mechanisms of calorie restriction's protection against age-related sclerosis
Chiarpotto, E., Bergamini, E., & Poli, G. (2006) · IUBMB Life · doi:10.1080/15216540601106365 · Cited by 12
“A 40% calorie restriction was shown to reduce the dimension and progression of atherosclerotic lesions in the aorta of Apo-E-deficient mice in parallel to a decrease in oxidative stress parameters ( 71 ).”
BackgroundO efeito da restrição calórica na longevidade
Genaro, P. D. S., Sarkis, K. S., & Martini, L. A. (2009) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302009000500019 · Cited by 14
Mechanistic perspectives of calorie restriction on vascular homeostasis
Liu, Y., Chen, H., & Liu, D. (2014) · Science China Life Sciences · doi:10.1007/s11427-014-4709-z · Cited by 10
Inflammation in Aging Processes
Finch, C. E. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-378638-8.00012-9 · Cited by 10
Forte, M., Rodolico, D., Ameri, P., Catalucci, D., Chimenti, C., Crotti, L., Schirone, L., Pingitore, A., Torella, D., Iacovone, G., et al. (2022) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000001397 · Cited by 10
Adhikari, H., Patel, P., Javvaji, N., Crabtree, M. J., & Simon, J. N. (2025) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2025.14 · Cited by 11
Calorie restriction in mice does not affect LDL reverse cholesterol transport in vivo
Stein, O. T., Dabach, Y., Halperin, G., Ben-Naim, M., & Stein, Y. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01313-5 · Cited by 8
Zhou, L., Yang, D., Wu, D. F., Guo, Z. M., Okoro, E. U., & Yang, H. C. (2013) · ISRN Pharmacology · doi:10.1155/2013/847310 · Cited by 7
“, Melville, NY), as described previously [11].”
BackgroundMethodChen, A., & Yang, L. Z. H. (2010) · Journal of Bioanalysis & Biomedicine · doi:10.4172/1948-593x.1000031 · Cited by 7
“Similarly, mice deficient in ApoE gene (ApoE-/-) or mice expressing ApoB48 but lacking ApoE and ApoB100 (ApoE-/-/B48/48) develop hypercholesterolemia due to increased ApoB48-carrying lipoproteins (Piedrahita et al., 1992; Guo et al., 2002; Farese et al., 1996).”
BackgroundMethodEffects of age and caloric restriction on the cardiac and coronary response to endothelin-1 in rats
Granado, M., Rubio, C., Amor, S., Monge, L., Fernández, N., Carreño‐Tarragona, G., Carrascosa, J. M., & Garcı́a-Villalón, Á. L. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.018 · Cited by 6
“Dietary restriction has beneficial effects on the cardiovascular system which seems to be mediated, at least in part, by an attenuation of the agerelated increase in inflammation (Guo et al., 2002) and oxidative stress (Sohal and Weindruch, 1996).”
BackgroundDietary factors in atherogenesis
Wilson, M. G., & Thomas, D. R. (2003) · Current Atherosclerosis Reports · doi:10.1007/s11883-003-0056-4 · Cited by 6
“ApoE-deficient mice on a low-calorie and oxysterol-poor diet exhibit a reduction in lipid hydroperoxide content and reactive molecular oxygen generation within the arterial wall [ 17 ].”
Chevli, P. A., Mirzai, S., Kazibwe, R., Kingsley, J., Wood, A. C., Yeboah, J., Slipczuk, L. N., Mehta, A., Bhatia, H. S., Pandey, A., et al. (2026) · Journal of the American Heart Association · doi:10.1161/jaha.125.042582 · Cited by 5
“25,26 These findings underscore the complex and possibly context-dependent role of KBs in cardiometabolic health.”
Lapenna, D., Ciofani, G., Cuccurullo, C., Neri, M., Giamberardino, M. A., & Cuccurullo, F. (2012) · Free Radical Research · doi:10.3109/10715762.2012.719613 · Cited by 5
“Regarding vascular H 2 O 2 , it is overproduced at levels in the hundreds of micromolar range in dyslipidemia and hypertension [19,20].”
BackgroundCoronary atherosclerosis: Significance of autophagic armour
Arora, M. (2012) · World Journal of Cardiology · doi:10.4330/wjc.v4.i9.271 · Cited by 5
Shimba, Y., Senda, R., Katayama, K., Morita, A., Ikeda, M., Kamei, Y., & Miura, S. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.01.001 · Cited by 4
CHRONIC LITHIUM TREATMENT PREVENT ANXIETY-LIKE BEHAVIOR RELATED TO DIETARY RESTRICTION
Ferreira, F. R., Spini, V. B. M. G., Ribeiro, G. D. C. C., & Paduani, G. F. (2009) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 4
Lapenna, D., Ciofani, G., Pierdomenico, S. D., Giamberardino, M. A., & Cuccurullo, F. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.11.081 · Cited by 4
“evidence of atherogenic effects of EC-SOD and CuZnSOD in hyperlipidemic conditions [29,30], which notably induce vascular H2O2 overproduction [31].”
BackgroundWu, D., Yang, H., Zhao, Y., Sharan, C., Goodwin, J. S., Zhou, L., Guo, Y., & Guo, Z. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.134833 · Cited by 4
“Likewise, ApoE-deficient (ApoE / ) mice manifest elevated plasma ApoB48-containing lipoproteins and develop atherosclerosis in a manner that resembles the human disease (Piedrahita et al., 1992; Guo et al., 2002).”
BackgroundCaloric Restriction and Cardiovascular Disease
Csiszár, A., de Cabo, R., & Ungvari, Z. I. (2010) · Springer eBooks · doi:10.1007/978-90-481-8556-6_15 · Cited by 4
Intense Caloric Restriction from Birth Prevents Cardiovascular Aging in Rats
Melo, D. D. S., Pereira, L. C., SANTOS, C. D. S., Mendes, B. F., Konig, I. F. M., Garcia, B. C. C., Queiroz, I. P., Moreno, L. G., Cassilhas, R. C., Esteves, E. A., et al. (2023) · Rejuvenation Research · doi:10.1089/rej.2023.0032 · Cited by 3
Metadata
- Authors
- Guo, Z., Mitchell-Raymundo, F., Yang, H., Ikeno, Y., Nelson, J., Diaz, V., Richardson, A., & Reddick, R.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Guo, ZhongMao
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 123
- Issue
- 8
- Pages
- 1121-1131
- ISSN
- 0047-6374 (ISSN-L)
- OpenAlex
- W2034827383
- Cited by
- 121
- References
- 60
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health
- National Institute on Aging (AG16998, P01 AG-13319, R01AG016998)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- dietary restriction, caloric restriction, atherosclerosis, ApoE-deficient mice, oxidative stress, lipid peroxidation, superoxide, hydrogen peroxide, aortic lesions, foam cells, antiatherogenic effects, aging
- MeSH terms
- Animals, Aorta, Apolipoproteins E, Arteriosclerosis, Energy Intake, Cholesterol, Diet, Disease Models, Animal, Hydrogen Peroxide, Lipoproteins, LDL, Male, Superoxides, Lipid Peroxidation, Mice, Knockout, Oxidative Stress, Mice
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