{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:07:54Z","timestamp":1790939274386,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,4,6]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in the progression of atherosclerosis is unknown. In this report, we first demonstrate that intimal vessels occur in advanced lesions of apolipoprotein E\u2013deficient (apoE \u2212\/\u2212) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE \u2212\/\u2212 mice.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014ApoE \u2212\/\u2212 mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant mouse endostatin, 20 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 d\n            <jats:sup>\u22121<\/jats:sup>\n            ; group 2, fumagillin analogue TNP-470, 30 mg\/kg every other day; and group 3, control animals that received a similar volume of buffer. Average cholesterol levels were similar in all groups. Plaque areas were quantified at the aortic origin. Median plaque area before treatment was 0.250 mm\n            <jats:sup>2<\/jats:sup>\n            (range, 0.170 to 0.348; n=10). Median plaque areas were 0.321 (0.238 to 0.412; n=10), 0.402 (0.248 to 0.533; n=15), and 0.751 mm\n            <jats:sup>2<\/jats:sup>\n            (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (\n            <jats:italic>P<\/jats:italic>\n            \u22640.0001). Therefore, endostatin and TNP-470 inhibited plaque growth during the treatment period by 85% and 70%. Intimal smooth muscle cell contents of plaques from control and treated mice were similar.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE \u2212\/\u2212 mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.13.1726","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"1726-1732","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":495,"title":["Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E\u2013Deficient Mice"],"prefix":"10.1161","volume":"99","author":[{"given":"Karen S.","family":"Moulton","sequence":"first","affiliation":[{"name":"From the Surgical Research Laboratory (K.S.M., E.F., J.F.), Children\u2019s Hospital, Boston Mass; Cardiovascular Division (K.S.M.), Brigham and Women\u2019s Hospital, Boston, Mass; Harvard Medical School (E.H.), Boston, Mass; the Department of Anatomy (M.A.K.), University of Mainz, Mainz, Germany; and the Department of Medicine (W.P.), University of California, San Diego, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Heller","sequence":"additional","affiliation":[{"name":"From the Surgical Research Laboratory (K.S.M., E.F., J.F.), Children\u2019s Hospital, Boston Mass; Cardiovascular Division (K.S.M.), Brigham and Women\u2019s Hospital, Boston, Mass; Harvard Medical School (E.H.), Boston, Mass; the Department of Anatomy (M.A.K.), University of Mainz, Mainz, Germany; and the Department of Medicine (W.P.), University of California, San Diego, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz A.","family":"Konerding","sequence":"additional","affiliation":[{"name":"From the Surgical Research Laboratory (K.S.M., E.F., J.F.), Children\u2019s Hospital, Boston Mass; Cardiovascular Division (K.S.M.), Brigham and Women\u2019s Hospital, Boston, Mass; Harvard Medical School (E.H.), Boston, Mass; the Department of Anatomy (M.A.K.), University of Mainz, Mainz, Germany; and the Department of Medicine (W.P.), University of California, San Diego, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Flynn","sequence":"additional","affiliation":[{"name":"From the Surgical Research Laboratory (K.S.M., E.F., J.F.), Children\u2019s Hospital, Boston Mass; Cardiovascular Division (K.S.M.), Brigham and Women\u2019s Hospital, Boston, Mass; Harvard Medical School (E.H.), Boston, Mass; the Department of Anatomy (M.A.K.), University of Mainz, Mainz, Germany; and the Department of Medicine (W.P.), University of California, San Diego, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wulf","family":"Palinski","sequence":"additional","affiliation":[{"name":"From the Surgical Research Laboratory (K.S.M., E.F., J.F.), Children\u2019s Hospital, Boston Mass; Cardiovascular Division (K.S.M.), Brigham and Women\u2019s Hospital, Boston, Mass; Harvard Medical School (E.H.), Boston, Mass; the Department of Anatomy (M.A.K.), University of Mainz, Mainz, Germany; and the Department of Medicine (W.P.), University of California, San Diego, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judah","family":"Folkman","sequence":"additional","affiliation":[{"name":"From the Surgical Research Laboratory (K.S.M., E.F., J.F.), Children\u2019s Hospital, Boston Mass; Cardiovascular Division (K.S.M.), Brigham and Women\u2019s Hospital, Boston, Mass; Harvard Medical School (E.H.), Boston, Mass; the Department of Anatomy (M.A.K.), University of Mainz, Mainz, Germany; and the Department of Medicine (W.P.), University of California, San Diego, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198401193100307"},{"key":"e_1_3_2_2_2","first-page":"454","volume":"13","year":"1876","unstructured":"Koester W. 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