Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis.
Publication/Presentation Date
4-15-2003
Abstract
Plaque angiogenesis promotes the growth of atheromas, but the functions of plaque capillaries are not fully determined. Neovascularization may act as a conduit for the entry of leukocytes into sites of chronic inflammation. We observe vasa vasorum density correlates highly with the extent of inflammatory cells, not the size of atheromas in apolipoprotein E-deficient mice. We show atherosclerotic aortas contain activities that promote angiogenesis. The angiogenesis inhibitor angiostatin reduces plaque angiogenesis and inhibits atherosclerosis. Macrophages in the plaque and around vasa vasorum are reduced, but we detect no direct effect of angiostatin on monocytes. After angiogenesis blockade in vivo, the angiogenic potential of atherosclerotic tissue is suppressed. Activated macrophages stimulate angiogenesis that can further recruit inflammatory cells and more angiogenesis. Our findings demonstrate that late-stage inhibition of angiogenesis can interrupt this positive feedback cycle. Inhibition of plaque angiogenesis and the secondary reduction of macrophages may have beneficial effects on plaque stability.
Volume
100
Issue
8
First Page
4736
Last Page
4741
ISSN
0027-8424
Published In/Presented At
Moulton, K. S., Vakili, K., Zurakowski, D., Soliman, M., Butterfield, C., Sylvin, E., Lo, K. M., Gillies, S., Javaherian, K., & Folkman, J. (2003). Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proceedings of the National Academy of Sciences of the United States of America, 100(8), 4736–4741. https://doi.org/10.1073/pnas.0730843100
Disciplines
Medicine and Health Sciences
PubMedID
12682294
Department(s)
Department of Surgery
Document Type
Article