Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice


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 (Rb(del) mice) and control littermates (Rb(fl) mice). After 12 wk feeding a cholesterol-rich diet, the Rb(del) 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.

More about this publication

FASEB journal: official publication of the Federation of American Societies for Experimental Biology
  • Volume 20
  • Issue nr. 7
  • Pages 953-5
  • Publication date 01-05-2006

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