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Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis.


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.

SUBMITTER: Moulton KS 

PROVIDER: S-EPMC153625 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

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Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis.

Moulton Karen S KS   Vakili Khashayar K   Zurakowski David D   Soliman Mohsin M   Butterfield Catherine C   Sylvin Erik E   Lo Kin-Ming KM   Gillies Stephen S   Javaherian Kashi K   Folkman Judah J  

Proceedings of the National Academy of Sciences of the United States of America 20030407 8


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 p  ...[more]

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