The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [106]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Angiogenesis in cancer, vascular, rheumatoid and other disease
Folkman, J. (1995) · Nature Medicine · doi:10.1038/nm0195-27 · Cited by 7,627
Self-citationRidker, P. M., Hennekens, C. H., Buring, J. E., & Rifai, N. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003233421202 · Cited by 5,850
OʼReilly, M. (1994) · Cell · doi:10.1016/0092-8674(94)90200-3 · Cited by 3,344
Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z., et al. (2000) · Nature Cell Biology · doi:10.1038/35036374 · Cited by 2,797
Söker, S., Takashima, S., Miao, H. Q., Neufeld, G., & Klagsbrun, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81402-6 · Cited by 2,493
Gu, L., Okada, Y., Clinton, S. K., Gerard, C. J., Sukhova, G. K., Libby, P., & Rollins, B. J. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80139-2 · Cited by 1,574
Barleon, B., Sozzani, S., Zhou, D., Weich, H., Mantovani, A., & Marmé, D. (1996) · Blood · doi:10.1182/blood.v87.8.3336.bloodjournal8783336 · Cited by 1,350
A major role for VCAM-1, but not ICAM-1, in early atherosclerosis
Cybulsky, M. I., Iiyama, K., Li, H., Zhu, S.-N., Chen, M., Iiyama, M., Davis, V., Gutierrez-Ramos, J.-C., Connelly, P. W., & Milstone, D. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11871 · Cited by 1,244
Davies, M. J., Richardson, P. D., Woolf, N., Katz, D. R., & Mann, J. (1993) · Heart · doi:10.1136/hrt.69.5.377 · Cited by 1,127
Flagged first, then by citations
Research works printed but not linked: 5
- J C Paterson Arch Pathol 25, 474–487 (1938).
- 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).
- R F Nicosia, A Ottinetti Lab Invest 63, 115–122 (1990).
- J Fang, L Yan, Y Shing, M A Moses Cancer Res 61, 5731–5735 (2001).
- R F Nicosia, Y J Lin, D Hazelton, X Qian Am J Pathol 151, 1379–1386 (1997).
Cited by
Sorted by citations
Items 601–649 of 649
The Biology of Non-Native Proteins
Herczenik, E. (2009) · Amyloid · doi:10.1080/13506120902879996
Vascular inflammation : Implications for microvascular reconstructive surgery after irradiation
Halle, M. (2010) · Figshare
Nanotechnology as a basis for the vascular treatment of atherosclerosis
SLEVIN, M. A., Badimón, L., Olivares, M. G., Morrison, M., & Krupiński, J. (2011) · International Journal of Nanotechnology · doi:10.1504/ijnt.2011.041434
Kwan, S. Y. (2011) · KiltHub Repository · doi:10.1184/r1/6723587
Targeted Nanoparticles for Molecular Imaging and Therapy
Caruthers, S. D., Wickline, S. A., & Lanza, G. M. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/1-4020-4384-8_19
Stem Cells and Atherosclerosis
Traverse, J. H. (2011) · Springer eBooks · doi:10.1007/978-1-4614-1475-9_12
Tirunal, S. C., & Chitra, S. (2012)
Zagorchev, M.-K. L. (2010)
Cardiac magnetic resonance detection of the human carotid: A new lens on neovascularization?
Shah, R. V., & Murthy, V. L. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.12.003
Nonlinear Contrast Intravascular Ultrasound
Goertz, D. E., Frijlink, M. E., de Jong, N., & van der Steen, A. F. W. (2011) · Springer eBooks · doi:10.1007/978-1-84882-688-5_8
Mechanisms of angiogenesis and lymphangiogenesis in calcific aortic valve stenosis
Syväranta, S. (2013) · Työväentutkimus Vuosikirja
Einfluß von Thalidomid auf die Atherogenese im Tiermodell der ApoE-/-/LDL-/--Doppel- Knockout Maus
Gunkel, I. A., & Justus Liebig University Giessen (2012) · University writing server of the Justus Liebig University Giessen (Justus-Liebig-Universität Gießen) · doi:10.22029/jlupub-13773
Biomedical Computing in Complex Advanced Systems
Kakadiaris, I. A., & Shah, S. K. (2010) · Springer eBooks · doi:10.1007/978-1-4419-6012-2_15
Gadolinium-enhanced plaque imaging
Kerwin, W. S. (2006) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544941.022
approach to experimental colitis Angiogenesis blockade as a new therapeutic
Mazar, A. P., Fiocchi, C., Redline, R. W., Levine, A. D., Danese, S., Spencer, D. M., Beck, I., & Marian, L. (2008)
Neoangiogênese na aterosclerose: modulação por lípides nitrados
Rudnicki, M. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.9.2016.tde-26072016-164413
Immunopathogenic mechanisms of Coronary Artery Disease and plaque destabilization
Smith, C. (2008) · NORA - Norwegian Open Research Archives
Treatment of Vulnerable Plaques
Brieger, D. B., Freedman, S., Kritharides, L., & Lowe, H. C. (2004) · CRC Press eBooks · doi:10.1201/9781420037883.ch10
IVUS and IVUS-derived methods for vulnerable plaque assessment
Kaple, R., Maehara, A., & Mintz, G. S. (2009) · CRC Press eBooks · doi:10.3109/9781841847214-13
Animal models of vulnerable plaque
Granada, J. F., & Schwartz, R. S. (2007) · CRC Press eBooks · doi:10.3109/9781439804537-11
Martin, K. H. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/qwdt-wv49
PET/MR imaging of hypoxic atherosclerotic plaque using 64Cu-ATSM
Nie, X. (2017) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7m9072q
Angiogenesis and Atherosclerosis
Mathur, P., Pant, S., Deshmukh, A. J., Kattoor, A. J., & Mehta, J. L. (2017) · Springer eBooks · doi:10.1007/978-3-319-61115-0_16
Molecular Imaging of Inflammation and Intraplaque Vasa Vasorum
ten Kate, G. L., van den Oord, S. C. H., Sijbrands, E. J. G., van der Steen, A. F. W., & Schinkel, A. F. L. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7425-8_24
Hughes, M. S., Caruthers, S. D., Tran, T., Marsh, J. N., Wallace, K. D., Cyrus, T., Partlow, K. C., Scott, M. J., Lijowski, M., Neubauer, A. M., et al. (2008) · Proceedings of the IEEE
Characterization of the Arterial Adventitia as a Sonic Hedgehog Responsive Niche
Hoglund, V. J. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/ehzc-b587
Atherosclerosis and Vascular Imaging 2016
Henein, M. Y. (2017) · MDPI eBooks · doi:10.3390/books978-3-03842-433-8
Pathobiology of Vascular Disease
Tillman, B. W., & Geary, R. L. (2008) · Springer eBooks · doi:10.1007/978-0-387-68113-9_62
Gabbiani, G. (2006) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1003489.374193
Liu, M., Yin, Y., Zheng, M., Shi, X.-C., Liu, D., Liu, D.-Y., Liu, G., & Wei, M. (2022) · Research Square · doi:10.21203/rs.3.rs-1476467/v1
RetractedAtherosclerosis: cell biology and lipoproteins
Eriksson, E. E. (2006) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000226130.25252.5c
Mack, C. P. (2015) · Atherosclerosis · doi:10.1002/9781118828533.ch11
;;;;;;;;; (2004) · Journal of Life Science · doi:10.5352/jls.2004.14.5.874
君枝, 田., & 政隆, 佐. (2009) · Journal of JCS Cardiologists · doi:10.1253/jjcsc.17.1_3
Jiang, S., Guo, J., Yin, Y.-W., Fang, C., Wang, J., Wang, Y., Lei, F., Sun, S., Pei, X., Jia, R., et al. (2022) · Cardiology Discovery · doi:10.1097/cd9.0000000000000054
Pathology of Vascular Remodeling -Molecular Mechanism of Functional Angiogenesis-
Sueishi, K. (2004) · The Japanese Journal of Phlebology · doi:10.7134/phlebol.15-4-277
Neue Wege zur zielgerichteten Prävention und Behandlung der Atherosklerose
Haverich, A., & Boyle, E. C. (2023) · Springer eBooks · doi:10.1007/978-3-031-31766-8_6
Belastendes Beweismaterial für die Rolle der Mikrozirkulation bei der Atherosklerose
Haverich, A., & Boyle, E. C. (2023) · Springer eBooks · doi:10.1007/978-3-031-31766-8_4
Eltemamy, M., Namushi, R., & Saravanan, N. (2023) · Bleeding Thrombosis and Vascular Biology · doi:10.4081/btvb.2023.79
The Process of Atheroma Growth, Vulnerability, and Rupture
Watanabe, T., & Fan, J. (2025) · Springer eBooks · doi:10.1007/978-981-96-3675-4_13
Gianopoulos, I., & Daskalopoulou, S. S. (2025) · Hellenic Journal of Cardiology · doi:10.1016/j.hjc.2025.08.002
Atherosclerosis, and morphology and stability of carotid artery plaque
Mahmood, D. N., & Forbes, T. L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13865-2.00004-4
Proteins of plasminogen/plasmin system: multifaceted roles in health and disease
Tykhomyrov, A. A., Yusova, O. I., Kapustianenko, L. G., Patalakh, I. I., Yatsenko, T., V. L., B., & Grynenko, T. V. (2025) · The Ukrainian Biochemical Journal · doi:10.15407/ubj97.05.072
動脈硬化研究の進歩 : 動脈硬化と血管新生(循環器学2004年の進歩)
克夫, 居. (2005) · Journal of JCS Cardiologists · doi:10.1253/jjcsc.13.1_91
Blood vessels at the crossroads: angiogenesis in the intersection of HIV and atherosclerosis
Domingo, P., Prieto, P., Giralt, M., Mauricio, D., & Fernández, E. C. (2026) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2026.03.007
Bories, G. F. P. (2011) · theses.fr (ABES) · doi:10.70675/81757398zf42fz45dcz8424z3f14e050bfb4
The Regulation of Vascular Wall Cells by a TLR Ligand and Gp130 Cytokines
Schnittker, D. L. K. (2012) · MacSphere (McMaster University) · doi:10.71548/16578
Metadata
- 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
- Publisher
- National Academy of Sciences
- Published
- 2003-04-07
- Volume
- 100
- Issue
- 8
- Pages
- 4736-4741
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC153625
- OpenAlex
- W2146672236
- Semantic Scholar
- 82c000d66a80c8c81b76c493b4ef41413cde3f9b
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
