{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:00:57Z","timestamp":1788282057252,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Vasa vasorum are angiogenic in advanced stages of human atherosclerosis and hypercholesterolemic mouse models. Fibroblast growth factor-2 (FGF-2) is the predominant angiogenic growth factor in the adventitia and plaque of hypercholesterolemic low-density lipoprotein receptor\u2013deficient\/apolipoprotein B\n              <jats:sup>100\/100<\/jats:sup>\n              mice (DKO). FGF-2 seems to play a role in the formation of a distinct vasa vasorum network. This study examined the vasa vasorum structure and its relationship to FGF-2.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              DKO mice treated with saline, antiangiogenic recombinant plasminogen activator inhibitor-1\n              <jats:sub>23<\/jats:sub>\n              (rPAI-1\n              <jats:sub>23<\/jats:sub>\n              ), or soluble FGF receptor 1 were perfused with fluorescein-labeled\n              <jats:italic>Lycopersicon esculentum<\/jats:italic>\n              lectin. Confocal images of FGF-2\u2013probed descending aorta adventitia show that angiogenic vasa vasorum form a plexus-like network in saline-treated DKO similar to the FGF-2 pattern of distribution. Mice treated with rPAI-1\n              <jats:sub>23<\/jats:sub>\n              and soluble FGF receptor 1 lack a plexus; FGF-2 and vasa vasorum density and area are significantly reduced. A perlecan\/FGF-2 complex is critical for plexus stability. Excess plasmin produced in rPAI-1\n              <jats:sub>23<\/jats:sub>\n              -treated DKO mice degrades perlecan and destabilizes the plexus. Plasmin activity and plaque size measured in DKO and DKO\/plasminogen activator inhibitor-1\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>\/\u2212<\/jats:sup>\n              mice demonstrate that elevated plasmin activity contributes to reduced plaque size.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>An FGF-2\/perlecan complex is required for vasa vasorum plexus stability. Elevated plasmin activity plays a significant inhibitory role in vasa vasorum plexus and plaque development.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.252544","type":"journal-article","created":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T10:44:38Z","timestamp":1347705878000},"page":"2644-2651","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Fibroblast Growth Factor-2 Is Required for Vasa Vasorum Plexus Stability in Hypercholesterolemic Mice"],"prefix":"10.1161","volume":"32","author":[{"given":"Jessica I.","family":"Mollmark","sequence":"first","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.-H.","family":"Park","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Katzenell","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Shipman","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubomir G.","family":"Zagorchev","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Simons","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jo","family":"Mulligan-Kehoe","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","first-page":"225","article-title":"Role of vasa vasorum in nourishment of the aorta.","volume":"16","author":"Heistad DD","year":"1979","unstructured":"Heistad DD, Marcus ML. 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