Accelerated Lipid-Induced Atherogenesis in Galectin-3-Deficient Mice: Role of Lipoxidation via Receptor-Mediated Mechanisms
Abstract
OBJECTIVE: Modified lipoproteins, particularly oxidized LDLs, are believed to evoke an inflammatory response which participates in all stages of atherosclerosis. Disposal of these particles is mediated through receptors which may trigger proinflammatory signaling pathways leading to vascular injury. This study was aimed at assessing the role in atherogenesis of one of these receptors, galectin-3. METHODS AND RESULTS: Galectin-3-deficient and wild-type mice were fed an atherogenic diet or standard chow for 8 months. Lesion area and length were higher in galectin-3-deficient versus wild-type mice. At the level of the aortic sinus, wild-type animals showed only fatty streaks, whereas galectin-3-deficient mice developed complex lesions, associated with extensive inflammatory changes. This was indicated by the presence of T lymphocytes with activated Th1-phenotype and by more marked monocyte-macrophage infiltration, inflammatory mediator expression, vascular cell apoptosis, and proinflammatory transcription factor activation. Increased accumulation of oxidixed LDLs and lipoxidation products and upregulation of other receptors for these compounds, including the proinflammatory RAGE, were detected in galectin-3-deficient versus wild-type mice. CONCLUSIONS: These data suggest a unique protective role for galectin-3 in the uptake and effective removal of modified lipoproteins, with concurrent downregulation of proinflammatory pathways responsible for atherosclerosis initiation and progression.
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In patients with coronary artery disease, plasma β-carotene, but not lycopene, was inversely correlated with plasma CRP concentrations.
“In patients with coronary artery disease, plasma concentrations of b-carotene, but not lycopene, were inversely correlated with plasma CRP concentrations (777) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [777]
Cites
The immune response in atherosclerosis: a double-edged sword
Hansson, G. K., & Libby, P. (2006) · Nature reviews. Immunology · doi:10.1038/nri1882 · Cited by 2,176 · see citing works
Galectin-3: An open-ended story
Dumić, J., Dabelić, S., & Flögel, M. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2005.12.020 · Cited by 1,171 · see citing works
INFLAMMATION AND ATHEROSCLEROSIS
Hansson, G. K., Robertson, A.-K. L., & Söderberg‐Nauclér, C. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100100 · Cited by 1,049 · see citing works
Frostegård, J., Ulfgren, A., Nyberg, P., Hedin, U., Swedenborg, J., Andersson, U., & Hansson, G. K. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00011-8 · Cited by 1,002 · see citing works
Quantitative assessment of atherosclerotic lesions in mice
Paigen, B. J., Morrow, A., Holmes, P. A., Mitchell, D., & Williams, R. A. (1987) · Atherosclerosis · doi:10.1016/0021-9150(87)90202-4 · Cited by 952 · see citing works
Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation
Demetriou, M., Granovsky, M., Quaggin, S., & Dennis, J. W. (2001) · Nature · doi:10.1038/35055582 · Cited by 901 · see citing works
Integration of metabolism and inflammation by lipid-activated nuclear receptors
Bensinger, S. J., & Tontonoz, P. (2008) · Nature · doi:10.1038/nature07202 · Cited by 813 · see citing works
Negre‐Salvayre, A., Coatrieux, C., Ingueneau, C., & Salvayre, R. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707395 · Cited by 641 · see citing works
Consequences and Therapeutic Implications of Macrophage Apoptosis in Atherosclerosis
Tabas, I. A. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000184783.04864.9f · Cited by 641 · see citing works
Variation in susceptibility to atherosclerosis among inbred strains of mice
Paigen, B. J., Morrow, A. L., Brandon, C. W., MITCHELL, D., & HOLMES, P. (1985) · Atherosclerosis · doi:10.1016/0021-9150(85)90138-8 · Cited by 614 · see citing works
Scavenger Receptors in Atherosclerosis: Beyond Lipid Uptake
Moore, K. J., & Freeman, M. W. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000229218.97976.43 · Cited by 562 · see citing works
Regulation of Alternative Macrophage Activation by Galectin-3
MacKinnon, A. C., Farnworth, S. L., Hodkinson, P. S., Henderson, N. C., Atkinson, K. M., Leffler, H., Nilsson, U. J., Haslett, C., Forbes, S. J., & Sethi, T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2650 · Cited by 543 · see citing works
B, J. R. V. B., Buurman, W. A., & Griffioen, A. W. (2008) · Angiogenesis · doi:10.1007/s10456-008-9093-5 · Cited by 529 · see citing works
Critical role of galectin-3 in phagocytosis by macrophages
Sano, H., Hsu, D. K., Apgar, J. R., Yu, L., Sharma, B. B., Kuwabara, I., Izui, S., & Liu, F.-T. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317592 · Cited by 429 · see citing works
Targeted Disruption of the Galectin-3 Gene Results in Attenuated Peritoneal Inflammatory Responses
Hsu, D. K., Yang, R., Pan, Z. K., Yu, L., Salomon, D. R., Fung‐Leung, W., & Liu, F. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64975-9 · Cited by 428 · see citing works
Zhou, X., Paulsson, G. B., Stemme, S., & Hansson, G. K. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1216 · Cited by 414 · see citing works
CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis.
Fukumori, T., Takenaka, Y., Yoshii, T., Kim, H.-R. C., Hogan, V. A., Inohara, H., Kagawa, S., & Raz, A. (2003) · PubMed · Cited by 363 · see citing works
Basta, G. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.07.025 · Cited by 357 · see citing works
Papaspyridonos, M., McNeill, E., de Bono, J. P., Smith, A., Burnand, K. G., Channon, K. M., & Greaves, D. R. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.159160 · Cited by 238 · see citing works
Accelerated diabetic glomerulopathy in galectin‐3/AGE receptor 3 knockout mice
Pugliese, G., Pricci, F., Iacobini, C., Leto, G., Amadio, L., Barsotti, P., Frigeri, L. G., Hsu, D. K., Vlassara, H., Liu, F., et al. (2001) · The FASEB Journal · doi:10.1096/fj.01-0006com · Cited by 184 · see citing works
Self-citationOxidation‐specific epitopes are important targets of innate immunity
Chou, M. ‐., Hartvigsen, K., Hansen, L. F., Fogelstrand, L., Shaw, P. X., Boullier, A., Binder, C. J., & Witztum, J. L. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.01968.x · Cited by 179 · see citing works
Scavenger receptors for oxidized and glycated proteins
Horiuchi, S., Sakamoto, Y., & Sakai, M. (2003) · Amino Acids · doi:10.1007/s00726-003-0029-5 · Cited by 175 · see citing works
Seeing strangers or announcing “danger”: Galectin-3 in two models of innate immunity
Sato, S., & Nieminen, J. (2002) · Glycoconjugate Journal · doi:10.1023/b:glyc.0000014089.17121.cc · Cited by 147 · see citing works
Nachtigal, M., Ghaffar, A., & Mayer, E. P. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2008.070348 · Cited by 128 · see citing works
Galectin-3 expression in human atherosclerotic lesions.
Nachtigal, M., Al-Assaad, Z., Mayer, E. P., Kim, K., & Monsigny, M. L. P. (1998) · Europe PMC (PubMed Central) · Cited by 117 · see citing works
Iacobini, C., Menini, S., Oddi, G., Ricci, P. C., Amadio, L., Pricci, F., Olivieri, A., Sorcini, M., Mario, U. D., Pesce, C. M., et al. (2004) · The FASEB Journal · doi:10.1096/fj.04-2031fje · Cited by 112 · see citing works
Self-citationZhu, W., Sano, H., Nagai, R., et al. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4256 · Cited by 103 · see citing works
Maeda, N., Johnson, L. A., Kim, S., Hagaman, J. R., Friedman, M. H., & Reddick, R. L. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.12.006 · Cited by 72 · see citing works
Galectin‐3 gene (LGALS3) expression in experimental atherosclerosis and cultured smooth muscle cells
Arar, C., Gaudin, J., Capron, L., & Legrand, A. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00683-8 · Cited by 67 · see citing works
Vessel wall apoptosis and atherosclerotic plaque instability
Kavurma, M. M., Bhindi, R., Lowe, H. C., Chesterman, C. N., & Khachigian, L. M. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01120.x · Cited by 62 · see citing works
Toll-like receptors in atherosclerosis
Tobias, P. S., & Curtiss, L. K. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351453 · Cited by 54 · see citing works
Development of age-dependent glomerular lesions in galectin-3/AGE-receptor-3 knockout mice
Iacobini, C., Oddi, G., Menini, S., Amadio, L., Ricci, C., Pippo, C. D., Sorcini, M., Pricci, F., Pugliese, F. R., & Pugliese, G. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00435.2004 · Cited by 51 · see citing works
Self-citationNovel determinants of plaque instability
Cipollone, F., Fazia, M. L., & Mezzetti, A. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01355.x · Cited by 36 · see citing works
Papaspyridonos, M., de Bono, J., Smith, A., et al. (2008) · Research Portal (King's College London) · Cited by 21 · see citing works
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Dietary factors and low-grade inflammation in relation to overweight and obesity
Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098 · see citing works
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- Authors
- Iacobini, C., Menini, S., Ricci, C., Scipioni, A., Sansoni, V., Cordone, S., Taurino, M., Serino, M., Marano, G., Federici, M., Pricci, F., & Pugliese, G.
- Affiliations
- University of Rome Tor Vergata (IT)
- From the Department of Clinical Sciences (C.I., S.M., C.R., A.S., V.S., S.C., G.P.), “La Sapienza” University; Unit of Vascular Surgery (M.T.), Sant’Andrea Hospital; Laboratory of Molecular Medicine (M.S., M.F.), Department of Internal Medicine, “Tor Vergata” University; and Departments of Drug Research and Evaluation (G.M.) and Cell Biology and Neurosciences (F.P.), National Institute of Health of Italy, Rome, Italy.
- ORCID
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2009-06
- Volume
- 29
- Issue
- 6
- Pages
- 831-836
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2139842368
- Cited by
- 91
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 9 · 2012: 9
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- galectin-3, atherogenesis, atherosclerosis, oxidized LDL, modified lipoproteins, RAGE, monocyte/macrophage infiltration, vascular inflammation, atherogenic diet
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Aorta, Aortic Diseases, Aortitis, Chemotaxis, Leukocyte, Diet, Atherogenic, Disease Models, Animal, Female, Lipoproteins, LDL, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Monocytes, Receptors, Immunologic, Time Factors, Transcription Factors, Lipid Peroxidation, Signal Transduction, Apoptosis, Mice, Knockout, Oxidative Stress, Th1 Cells, Disease Progression, Inflammation Mediators, Galectin 3, Atherosclerosis, Receptors, Scavenger, Mice
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