Cited by 652Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismCerebrovascular and Carotid Artery Diseases

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

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Moulton, Karen S., Vakili, Khashayar, Zurakowski, David, Soliman, Mohsin, Butterfield, Catherine, Sylvin, Erik, Lo, Kin-Ming, Gillies, Stephen +2 more·2003·Proceedings of the National Academy of Sciences

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.

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Crossref · 10.1073/pnas.0730843100

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  • Small-molecule drugs such as TNP-470, endostatin or angiostatin reduced plaque angiogenesis and inhibited advanced atherosclerosis in APOE-knockout mice after 16 weeks of treatment.

    “Small-molecule drugs like the fumagillin analogue TNP-470, endostatin or angiostatin reduced plaque angiogenesis and inhibited advanced atherosclerosis in APOE-knockout mice after prolonged treatment for 16 weeks105,106.”

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Research works printed but not linked: 5

  1. J C Paterson Arch Pathol 25, 474–487 (1938).
  2. E R O'Brien, M R Garvin, R Dev, D K Stewart, T Hinohara, J B Simpson, S M Schwartz Am J Pathol 145, 883–894 (1994).
  3. R F Nicosia, A Ottinetti Lab Invest 63, 115–122 (1990).
  4. J Fang, L Yan, Y Shing, M A Moses Cancer Res 61, 5731–5735 (2001).
  5. R F Nicosia, Y J Lin, D Hazelton, X Qian Am J Pathol 151, 1379–1386 (1997).

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Authors
Moulton, K. S., Vakili, K., Zurakowski, D., Soliman, M., Butterfield, C., Sylvin, E., Lo, K.-M., Gillies, S., Javaherian, K., & Folkman, J.
Affiliations
Boston University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2003-04-07
Volume
100
Issue
8
Pages
4736-4741
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2146672236
Cited by
652
References
32
Citations by year
2026: 3 · 2025: 9 · 2024: 12 · 2023: 15 · 2022: 15 · 2021: 16 · 2020: 18 · 2019: 19 · 2018: 13 · 2017: 19 · 2016: 35 · 2015: 29 · 2014: 35 · 2013: 30 · 2012: 27
FWCI
14.61
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
Keywords
atherosclerosis, plaque neovascularization, angiogenesis inhibition, angiostatin, macrophage accumulation, vasa vasorum, ApoE-deficient mice, plaque stability, chronic inflammation, leukocyte recruitment, positive feedback loop
MeSH terms
Animals, Apolipoproteins E, Arteriosclerosis, Feedback, Inflammation, Lymphokines, Macrophages, Mice, Inbred C57BL, Monocytes, Neovascularization, Pathologic, Peptide Fragments, Plasminogen, Receptors, LDL, Vasa Vasorum, Endothelial Growth Factors, Mice, Knockout, Chemokine CCL2, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Angiostatins, Mice, In Vitro Techniques

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