Inflammation in Atherosclerosis: Transition From Theory to Practice
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Inflammation drives the formation, progression, and rupture of atherosclerotic plaques. Experimental studies have demonstrated that an inflammatory subset of monocytes/macrophages preferentially accumulate in atherosclerotic plaque and produce proinflammatory cytokines. T lymphocytes can contribute to inflammatory processes that promote thrombosis by stimulating production of collagen-degrading proteinases and the potent procoagulant tissue factor. Recent data link obesity, inflammation, and modifiers of atherosclerotic events, a nexus of growing clinical concern given the worldwide increase in the prevalence of obesity. Modulators of inflammation derived from visceral adipose tissue evoke production of acute phase reactants in the liver, implicated in thrombogenesis and clot stability. Additionally, C-reactive protein levels rise with increasing levels of visceral adipose tissue. Adipose tissue in obese mice contains increased numbers of macrophages and T lymphocytes, increased T lymphocyte activation, and increased interferon-gamma (IFN-gamma) expression. IFN-gamma deficiency in mice reduces production of inflammatory cytokines and inflammatory cell accumulation in adipose tissue. Another series of in vitro and in vivo mouse experiments affirmed that adiponectin, an adipocytokine, the plasma levels of which drop with obesity, acts as an endogenous antiinflammatory modulator of both innate and adaptive immunity in atherogenesis. Thus, accumulating experimental evidence supports a key role for inflammation as a link between risk factors for atherosclerosis and the biology that underlies the complications of this disease. The recent JUPITER trial supports the clinical utility of an assessment of inflammatory status in guiding intervention to limit cardiovascular events. Inflammation is thus moving from a theoretical concept to a tool that provides practical clinical utility in risk assessment and targeting of therapy.
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Innate and adaptive immune activation drives atherogenesis from early endothelial dysfunction to acute thrombotic complications.
“Activation of both innate and adaptive immunity actively contributes to the initiation and progression of atherogenesis, from early endothelial dysfunction to the development of acute thrombotic complications”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [149]
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Self-citationMolecular Imaging in the Clinical Arena
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Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease
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Self-citationIn vivo imaging of proteolytic enzyme activity using a novel molecular reporter.
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In Vivo Imaging of Proteolytic Activity in Atherosclerosis
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Role of Naturally Occurring CD4 + CD25 + Regulatory T Cells in Experimental Atherosclerosis
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Self-citationCD1d-dependent Activation of NKT Cells Aggravates Atherosclerosis
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Analysis of an expression profile of genes in the human adipose tissue
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Intertwining of thrombosis and inflammation in atherosclerosis
Croce, K., & Libby, P. (2007) · Current Opinion in Hematology · doi:10.1097/00062752-200701000-00011 · Cited by 285 · see citing works
Self-citationInokubo, Y., Hanada, H., Ishizaka, H., Fukushi, T., Kamada, T., & Okumura, K. (2001) · American Heart Journal · doi:10.1067/mhj.2001.112238 · Cited by 283 · see citing works
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The vulnerable atherosclerotic plaque
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Self-citationThe role of adaptive T cell immunity in atherosclerosis
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TH2 Predominant Immune Responses Prevail in Human Abdominal Aortic Aneurysm
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Self-citationPreparation of a Cathepsin D Sensitive Near-Infrared Fluorescence Probe for Imaging
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Adiponectin and Cardiovascular Disease
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Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction
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Real-Time Catheter Molecular Sensing of Inflammation in Proteolytically Active Atherosclerosis
Jaffer, F. A., Vinegoni, C., John, M. C., Aikawa, E. R., Gold, H. K., Finn, A. V., Ntziachristos, V., Libby, P., & Weissleder, R. (2008) · Circulation · doi:10.1161/circulationaha.108.785881 · Cited by 204 · see citing works
Self-citationLi, H., Cybulsky, M. I., Gimbrone, M. A., & Libby, P. (1993) · PubMed Central · Cited by 203 · see citing works
Self-citationOkamoto, Y., Folco, E. J. E., Minami, M., Wara, A. K., Feinberg, M. W., Sukhova, G. K., Colvin, R. A., Kihara, S., Funahashi, T., Luster, A. D., et al. (2007) · Circulation Research · doi:10.1161/circresaha.107.164988 · Cited by 202 · see citing works
Self-citationInflammation and Atherothrombosis
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Self-citationTh2-predominant inflammation and blockade of IFN-γ signaling induce aneurysms in allografted aortas
Shimizu, K., Shichiri, M., Libby, P., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19855 · Cited by 200 · see citing works
Self-citationSubstrate Hydrolysis by Matrix Metalloproteinase-9*
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Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis
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Self-citationAn, G., Wang, H., Tang, R., Yago, T., McDaniel, J. M., McGee, S., Huo, Y., & Xia, L. (2008) · Circulation · doi:10.1161/circulationaha.108.771048 · Cited by 186 · see citing works
Oxidation‐specific epitopes are important targets of innate immunity
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Self-citationRidker, P. M., MacFadyen, J. G., Fonseca, F. A. H., Genest, J. J., Gotto, A. M., Kastelein, J. J. P., Köenig, W., Libby, P., Lorenzatti, A. J., Nordestgaard, B. G., et al. (2009) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.109.848473 · Cited by 165 · see citing works
Self-citationApplications of Nanotechnology to Atherosclerosis, Thrombosis, and Vascular Biology
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Cytokines and cardiovascular disease
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The role of innate immunity in atherogenesis
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Mast cells: multipotent local effector cells in atherothrombosis
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van Wanrooij, E. J. A., de Jager, S. C. A., van Es, T., de Vos, P., Birch, H. L., Owen, D. A., Watson, R. J., Biessen, E. A. L., Chapman, G. A., van Berkel, T. J. C., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.147827 · Cited by 121 · see citing works
Han, S.-F., Liu, P., Zhang, W., et al. (2007) · Clinical Immunology · doi:10.1016/j.clim.2007.03.546 · Cited by 120 · see citing works
Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases
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Matrix Metalloproteinases Cleave Tissue Factor Pathway Inhibitor: Effects on coagulation
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Pöllänen, P. J., Karhunen, P. J., Mikkelsson, J., Laippala, P., Perola, M., Penttilä, A., Mattila, K. M., Koivula, T. A., & Lehtimäki, T. J. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq0901.095545 · Cited by 105 · see citing works
Fredrikson, G. N., Andersson, L. I. M., Söderberg, I., Dimayuga, P. C., Chyu, K., Shah, P. K., & Nilsson, J. Å. (2005) · Autoimmunity · doi:10.1080/08916930500050525 · Cited by 102 · see citing works
Fukumoto, Y., Deguchi, J.-O., Libby, P., Aikawa, E. R., Sakata, Y., Chin, M. T., Hill, C. C., Lawler, P. R., Varo, N., Schöen, F. J., et al. (2004) · Circulation · doi:10.1161/01.cir.0000143174.41810.10 · Cited by 98 · see citing works
Self-citationTang, P. C. Y., Yakimov, A. O., Teesdale, M. A., et al. (2005) · The FASEB Journal · doi:10.1096/fj.05-3671fje · Cited by 96 · see citing works
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Kume, T., Okura, H., Yamada, R., Kawamoto, T., Watanabe, N., Neishi, Y., Sadahira, Y., Akasaka, T., & Yoshida, K. (2009) · Circulation Journal · doi:10.1253/circj.cj-08-0733 · Cited by 81 · see citing works
Diversity of Denizens of the Atherosclerotic Plaque
Libby, P., Nahrendorf, M., Pittet, M. J., & Świrski, F. K. (2008) · Circulation · doi:10.1161/circulationaha.108.783068 · Cited by 77 · see citing works
Self-citationKashiwagi, M., Tanaka, A., Kitabata, H., et al. (2009) · Circulation Journal · doi:10.1253/circj.cj-08-0968 · Cited by 68 · see citing works
Mast Cells as Mediators and Modulators of Atherogenesis
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Self-citationMiller, D. T., Ridker, P. M., Libby, P., & Kwiatkowski, D. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.12.045 · Cited by 62 · see citing works
Self-citationMorishige, K. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00710-1 · Cited by 59 · see citing works
The Multiple Facets of the Fat Tissue
Rocha, V. Z., & Libby, P. (2008) · Thyroid · doi:10.1089/thy.2007.0296 · Cited by 59 · see citing works
Self-citationMatrix Metalloproteinases in Patients with Myocardial Infarction and Percutaneous Revascularization
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T cells in arteritis and atherosclerosis
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Relation of Obesity to Acute Myocardial Infarction in Japanese Patients
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Package Inserts Provide Inadequate Drug Information
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Introduction: Atherosclerosis as inflammation: a controversial concept becomes accepted
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Inhibition of Lipoprotein-Associated Phospholipase Activity by Darapladib
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CRP may be Superior to Anthropometric Markers of Obesity
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
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Chronic Inflammation in Obesity and the Metabolic Syndrome
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The inflammation highway: metabolism accelerates inflammatory traffic in obesity
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miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis
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Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling
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- Authors
- Libby, P., Okamoto, Y., Rocha, V. Z., & Folco, E.
- Affiliations
- Brigham and Women's Hospital (US)
- Nippon Medical School (JP)
- Venue
- Circulation Journal
- Publisher
- Japanese Circulation Society
- Published
- 2010
- Volume
- 74
- Issue
- 2
- Pages
- 213-220
- ISSN
- 1346-9843 (ISSN-L)
- 1347-4820
- OpenAlex
- W2147181044
- Cited by
- 799
- References
- 166
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 24 · 2023: 27 · 2022: 27 · 2021: 41 · 2020: 43 · 2019: 46 · 2018: 41 · 2017: 47 · 2016: 42 · 2015: 62 · 2014: 60 · 2013: 67 · 2012: 95
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- inflammation, atherosclerosis, atherosclerotic plaque rupture, monocytes/macrophages, T cells, thrombosis, tissue factor, obesity, visceral adipose tissue, C-reactive protein, interferon-gamma, adiponectin, acute phase proteins, atherogenesis, cardiovascular risk assessment, JUPITER trial
- MeSH terms
- Adipose Tissue, Animals, Anti-Inflammatory Agents, Cardiovascular Agents, Cardiovascular Diseases, Humans, Immunity, Innate, Inflammation, Monocytes, Obesity, Risk Factors, Thrombosis, Signal Transduction, Inflammation Mediators, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis, Adiponectin, Adaptive Immunity, Translational Research, Biomedical
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