Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice
Neovascularization 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-deficient (apoE -/-) mice. To test the hypot...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1999-04, Vol.99 (13), p.1726-1732 |
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| creator | MOULTON, K. S HELLER, E KONERDING, M. A FLYNN, E PALINSKI, W FOLKMAN, J |
| description | Neovascularization 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-deficient (apoE -/-) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE -/- mice.
ApoE -/- 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. kg-1. d-1; 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 mm2 (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 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P |
| doi_str_mv | 10.1161/01.cir.99.13.1726 |
| format | Article |
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ApoE -/- 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. kg-1. d-1; 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 mm2 (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 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P</=0.0001). 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.
Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.99.13.1726</identifier><identifier>PMID: 10190883</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Aorta, Thoracic - drug effects ; Aorta, Thoracic - pathology ; Apolipoproteins E - deficiency ; Apolipoproteins E - genetics ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Count - drug effects ; Cell Division - drug effects ; Collagen - pharmacology ; Cyclohexanes ; Endostatins ; Male ; Medical sciences ; Mice ; Mice, Knockout ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - pathology ; Neovascularization, Pathologic - pathology ; O-(Chloroacetylcarbamoyl)fumagillol ; Peptide Fragments - pharmacology ; Sesquiterpenes - pharmacology ; Time Factors ; Tunica Intima - drug effects ; Tunica Intima - pathology</subject><ispartof>Circulation (New York, N.Y.), 1999-04, Vol.99 (13), p.1726-1732</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Apr 6, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-c4e8ef379c0678778ada69caea2eceb4a3259a886256d9ffec2642c4264442903</citedby><cites>FETCH-LOGICAL-c552t-c4e8ef379c0678778ada69caea2eceb4a3259a886256d9ffec2642c4264442903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1739480$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10190883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MOULTON, K. S</creatorcontrib><creatorcontrib>HELLER, E</creatorcontrib><creatorcontrib>KONERDING, M. A</creatorcontrib><creatorcontrib>FLYNN, E</creatorcontrib><creatorcontrib>PALINSKI, W</creatorcontrib><creatorcontrib>FOLKMAN, J</creatorcontrib><title>Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Neovascularization 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-deficient (apoE -/-) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE -/- mice.
ApoE -/- 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. kg-1. d-1; 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 mm2 (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 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P</=0.0001). 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.
Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.</description><subject>Animals</subject><subject>Aorta, Thoracic - drug effects</subject><subject>Aorta, Thoracic - pathology</subject><subject>Apolipoproteins E - deficiency</subject><subject>Apolipoproteins E - genetics</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cell Count - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Collagen - pharmacology</subject><subject>Cyclohexanes</subject><subject>Endostatins</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>O-(Chloroacetylcarbamoyl)fumagillol</subject><subject>Peptide Fragments - pharmacology</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Time Factors</subject><subject>Tunica Intima - drug effects</subject><subject>Tunica Intima - pathology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU9r3DAQxUVJabZJP0AuRYTQm139s2Qdw5K0gdCWkJ6FVh5vFLySK8kN7bkfvAq7kNLLDAO_ebyZh9AZJS2lkn4ktHU-tVq3lLdUMfkKrWjHRCM6ro_QihCiG8UZO0Zvc36so-Sqe4OOKaGa9D1foT-XYevjFgJkn7EPD37jS0wZQxhiLrb4gGPC91--NUIRnGBYHFSu-J2dcID402a3TDb535WNAdsw4HmyPxbA2xSfykOFsZ3j5Oc4p1igjlfNAKN3HkLBO-_gFL0e7ZTh3aGfoO_XV_frz83t108368vbxnUdK40T0MPIlXZEql6p3g5WamfBMnCwEZazTtu-l6yTgx5HcEwK5kStQjBN-An6sNetRqrBXMzOZwfTZOshSzZSS1l1VQXP_wMf45JC9WYYZYoTTUSF6B5yKeacYDRzql9Jvwwl5jkfQ6hZ39wZrQ3l5jmfuvP-ILxsdjD8s7EPpAIXB6D-1U5jssH5_MIprkVP-F9vmZpL</recordid><startdate>19990406</startdate><enddate>19990406</enddate><creator>MOULTON, K. S</creator><creator>HELLER, E</creator><creator>KONERDING, M. A</creator><creator>FLYNN, E</creator><creator>PALINSKI, W</creator><creator>FOLKMAN, J</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19990406</creationdate><title>Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice</title><author>MOULTON, K. S ; HELLER, E ; KONERDING, M. A ; FLYNN, E ; PALINSKI, W ; FOLKMAN, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-c4e8ef379c0678778ada69caea2eceb4a3259a886256d9ffec2642c4264442903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Aorta, Thoracic - drug effects</topic><topic>Aorta, Thoracic - pathology</topic><topic>Apolipoproteins E - deficiency</topic><topic>Apolipoproteins E - genetics</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cell Count - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Collagen - pharmacology</topic><topic>Cyclohexanes</topic><topic>Endostatins</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>O-(Chloroacetylcarbamoyl)fumagillol</topic><topic>Peptide Fragments - pharmacology</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Time Factors</topic><topic>Tunica Intima - drug effects</topic><topic>Tunica Intima - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MOULTON, K. S</creatorcontrib><creatorcontrib>HELLER, E</creatorcontrib><creatorcontrib>KONERDING, M. A</creatorcontrib><creatorcontrib>FLYNN, E</creatorcontrib><creatorcontrib>PALINSKI, W</creatorcontrib><creatorcontrib>FOLKMAN, J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MOULTON, K. S</au><au>HELLER, E</au><au>KONERDING, M. A</au><au>FLYNN, E</au><au>PALINSKI, W</au><au>FOLKMAN, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1999-04-06</date><risdate>1999</risdate><volume>99</volume><issue>13</issue><spage>1726</spage><epage>1732</epage><pages>1726-1732</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Neovascularization 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-deficient (apoE -/-) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE -/- mice.
ApoE -/- 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. kg-1. d-1; 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 mm2 (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 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P</=0.0001). 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.
Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>10190883</pmid><doi>10.1161/01.cir.99.13.1726</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Aorta, Thoracic - drug effects Aorta, Thoracic - pathology Apolipoproteins E - deficiency Apolipoproteins E - genetics Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Count - drug effects Cell Division - drug effects Collagen - pharmacology Cyclohexanes Endostatins Male Medical sciences Mice Mice, Knockout Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - pathology Neovascularization, Pathologic - pathology O-(Chloroacetylcarbamoyl)fumagillol Peptide Fragments - pharmacology Sesquiterpenes - pharmacology Time Factors Tunica Intima - drug effects Tunica Intima - pathology |
| title | Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice |
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