Title
Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice
Author
Boesten, L.S.M.
Zadelaar, A.S.M.
van Nieuwkoop, A.
Hu, L.
Jonkers, J.
van de Water, B.
Gijbels, M.J.J.
van der Made, I.
de Winther, M.P.J.
Havekes, L.M.
van Vlijmen, B.J.M.
TNO Kwaliteit van Leven
Publication year
2006
Abstract
The cellular composition of an atherosclerotic lesion is determined by cell infiltration, proliferation, and apoptosis. The tumor suppressor gene retinoblastoma (Rb) has been shown to regulate both cell proliferation and cell death in many cell types. To study the role of macrophage Rb in the development of atherosclerosis, we used apoE-deficient mice with a macrophage-restricted deletion of Rb (Rbdel mice) and control littermates (Rbfl mice). After 12 wk feeding a cholesterol-rich diet, the Rbdel mice showed a 51% increase in atherosclerotic lesion area with a 39% increase in the relative number of advanced lesions. Atherosclerotic lesions showed a 13% decrease in relative macrophage area and a 46% increase in relative smooth muscle cell area, reflecting the more advanced state of the lesions. The increase in atherosclerosis was independent of in vitro macrophage modified lipoprotein uptake or cytokine production. Whereas macrophage-restricted Rb deletion did not affect lesional macrophage apoptosis, a clear 2.6-fold increase in lesional macrophage proliferation was observed. These studies demonstrate that macrophage Rb is a suppressing factor in the progression of atherosclerosis by reducing macrophage proliferation. © FASEB.
Subject
Biology
Biomedical Research
Apoptosis
Genetically altered mice
Proliferation
Apolipoprotein E
Animal cell
Animal experiment
Animal model
Animal tissue
Atherosclerosis
Cell proliferation
Cholesterol diet
Controlled study
Cytokine production
Disease course
Gene deletion
Immunohistochemistry
In vitro study
Macrophage
Male
Mouse
Protein transport
Smooth muscle fiber
Tumor suppressor gene
To reference this document use:
http://resolver.tudelft.nl/uuid:c391fc66-cb63-4183-8ad0-b0fdf9da7f03
DOI
https://doi.org/10.1096/fj.05-4530fje
TNO identifier
239263
ISSN
0892-6638
Source
FASEB Journal, 20 (7)
Document type
article