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Cited by 66Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismBiomarkers in Disease Mechanisms

Macrophage-Specific Expression of Mannose-Binding Lectin Controls Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice

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Matthijsen, Robert A., de Winther, Menno P.J., Kuipers, Dian, van der Made, Ingeborg, Weber, Christian, Herias, M. Veronica, Gijbels, Marion J.J., Buurman, Wim A.·2009·Circulation
DOI 10.1161/circulationaha.108.830661
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Abstract

Background— With consideration of the central role of the innate immune system in atherogenesis and mannose-binding lectin (MBL) as an innate regulator of immunity, the role of MBL in experimental and human atherosclerosis was assessed. Methods and Results— With the use of immunohistochemistry and polymerase chain reaction, deposition and gene expression of MBL-A and -C were assessed in murine atherosclerosis from mice deficient for the low-density lipoprotein receptor (LDLR −/− ) after 10 or 18 weeks of high-fat feeding. MBL was present and was produced in 10-week-old lesions, whereas deposition and gene expression were minimal after 18 weeks of high-fat feeding and absent in healthy vasculature. Interestingly, deposition of MBL-A and -C differed: MBL-A predominantly localized in upper medial layers, whereas MBL-C was found in and around intimal macrophages. To further study the role of local MBL production by monocytic cells in atherosclerosis, LDLR −/− mice with MBL-A and -C −/− monocytic cells were construed by bone marrow transplantation. Mice carrying MBL-A and -C double deficient macrophages had increased (30%) atherosclerotic lesions compared with wild-type controls ( P =0.015) after 10 weeks of high-fat diet. Subsequently, analysis of MBL deposition and gene expression in advanced human atherosclerotic lesions revealed the presence of MBL protein in ruptured but not stable atherosclerotic lesions. Putatively in agreement with murine data, no MBL gene expression could be detected in advanced human atherosclerotic lesions. Conclusions— These results are the first to show that MBL is abundantly present and locally produced during early atherogenesis. Local MBL expression, by myeloid cells, is shown to critically control development of atherosclerotic lesions.

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Authors
Matthijsen, R. A., de Winther, M. P. J., Kuipers, D., van der Made, I., Weber, C., Herias, M. V., Gijbels, M. J. J., & Buurman, W. A.
Affiliations
  • Maastricht University Medical Centre (NL)
  • From the Department of Surgery, Maastricht University Medical Centre and School for Nutrition and Metabolism, Maastricht, Netherlands (R.A.M., D.K., W.A.B.); Departments of Molecular Genetics (M.P.J.d.W., I.v.d.M., M.J.J.G.) and Pathology (M.V.H., M.J.G.), Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, Netherlands; and Institute for Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany (C.W.).
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-04-28
Volume
119
Issue
16
Pages
2188-2195
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.108.830661
OpenAlex
W2022249202
Cited by
66
References
0
Citations by year
2026: 2 · 2024: 4 · 2023: 4 · 2022: 1 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 9
FWCI
3.74
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords
mannose-binding lectin, atherosclerosis, low-density lipoprotein receptor deficiency, macrophages, innate immunity, atherogenesis, high-fat diet, bone marrow transplantation, myeloid cells
MeSH terms
Animals, Cholesterol, Female, Humans, Lipase, Macrophages, Mice, Inbred C57BL, Mice, Mutant Strains, Receptors, LDL, Gene Expression, Bone Marrow Transplantation, Mannose-Binding Lectin, Atherosclerosis, Mice

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