{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:47:34Z","timestamp":1753886854967,"version":"3.41.2"},"reference-count":79,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,11,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">We recently discovered a small endogenous peptide, peptide Lv, with the ability to activate vascular endothelial growth factor receptor 2 and its downstream signaling. As vascular endothelial growth factor through vascular endothelial growth factor receptor 2 contributes to normal development, vasodilation, angiogenesis, and pathogenesis of various diseases, we investigated the role of peptide Lv in vasodilation and developmental and pathological angiogenesis in this study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">The endothelial cell proliferation, migration, and 3\u2010dimensional sprouting assays were used to test the abilities of peptide Lv in angiogenesis in\u00a0vitro. The chick chorioallantoic membranes and early postnatal mice were used to examine its impact on developmental angiogenesis. The oxygen\u2010induced retinopathy and laser\u2010induced choroidal neovascularization mouse models were used for in\u00a0vivo pathological angiogenesis. The isolated porcine retinal and coronary arterioles were used for vasodilation assays. Peptide Lv elicited angiogenesis in\u00a0vitro and in\u00a0vivo. Peptide Lv and vascular endothelial growth factor acted synergistically in promoting endothelial cell proliferation. Peptide Lv\u2013elicited vasodilation was not completely dependent on nitric oxide, indicating that peptide Lv had vascular endothelial growth factor receptor 2\/nitric oxide\u2013independent targets. An antibody against peptide Lv, anti\u2010Lv, dampened vascular endothelial growth factor\u2013elicited endothelial proliferation and laser\u2010induced vascular leakage and choroidal neovascularization. While the pathological angiogenesis in mouse eyes with oxygen\u2010induced retinopathy was enhanced by exogenous peptide Lv, anti\u2010Lv dampened this process. Furthermore, deletion of peptide Lv in mice significantly decreased pathological neovascularization compared with their wild\u2010type littermates.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results demonstrate that peptide Lv plays a significant role in pathological angiogenesis but may be less critical during development. Peptide Lv is involved in pathological angiogenesis through vascular endothelial growth factor receptor 2\u2013dependent and \u2013independent pathways. As anti\u2010Lv dampened the pathological angiogenesis in the eye, anti\u2010Lv may have a therapeutic potential to treat pathological angiogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.013673","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T15:25:59Z","timestamp":1573226759000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Newly Identified Peptide, Peptide Lv, Promotes Pathological Angiogenesis"],"prefix":"10.1161","volume":"8","author":[{"given":"Liheng","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Veterinary Integrative Biosciences College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Ophthalmic Vascular Research Program College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colette A.","family":"Abbey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Huai","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Ophthalmic Vascular Research Program College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wankun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Ophthalmic Vascular Research Program College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayla J.","family":"Bayless","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis W.","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Ophthalmic Vascular Research Program College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Robert H.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Ophthalmic Vascular Research Program College of Medicine Texas A&amp;M University Health Science Center Bryan TX"},{"name":"Department of Ophthalmology Baylor Scott &amp; White Eye Institute Temple TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L.","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station TX"},{"name":"Department of Biology Blinn College Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lih","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Ophthalmic Vascular Research Program College of Medicine Texas A&amp;M University Health Science Center Bryan TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gladys Y.\u2010P.","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station TX"},{"name":"Texas A&amp;M Institute for Neuroscience Texas A&amp;M University College Station TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4652(200009)184:3<301::AID-JCP3>3.0.CO;2-H"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071419"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07039"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina54010008"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00706"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300507"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07524-x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-015-9477-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2015.05.004"},{"key":"e_1_3_2_11_2","first-page":"353","article-title":"Age\u2010related macular degeneration (AMD): pathogenesis and therapy","volume":"58","author":"Nowak JZ","year":"2006","unstructured":"Nowak JZ. Age\u2010related macular degeneration (AMD): pathogenesis and therapy. Pharmacol Rep. 2006;58:353\u2013363.","journal-title":"Pharmacol Rep"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(88)90052-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3164734"},{"key":"e_1_3_2_14_2","first-page":"262","article-title":"Fibroblastic overgrowth of persistent tunica vasculosa lentis in infants born prematurely: II. Report of cases\u2010clinical aspects","volume":"40","author":"Terry TL","year":"1942","unstructured":"Terry TL. Fibroblastic overgrowth of persistent tunica vasculosa lentis in infants born prematurely: II. Report of cases\u2010clinical aspects. Trans Am Ophthalmol Soc. 1942;40:262\u2013284.","journal-title":"Trans Am Ophthalmol Soc"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.164937"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3789217"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.05.001"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl239"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-653"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1911"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-0993-5"},{"key":"e_1_3_2_22_2","unstructured":"Gallemore RP Nguyen D. When anti\u2010VEGF treatment fails. Review of Ophthalmology. Published by Jobson Medicail Information; March 20 2008. Available at: http:\/\/www.reviewofophthalmology.com\/content\/d\/retinal_insider\/i\/1230\/c\/23141\/. Accessed April 20 2018."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2006.113902"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2014.50.12.2245587"},{"key":"e_1_3_2_25_2","first-page":"485","article-title":"Resistance to antivascular endothelial growth factor treatment in age\u2010related macular degeneration","volume":"7","author":"Tranos P","year":"2013","unstructured":"Tranos P, Vacalis A, Asteriadis S, Koukoula S, Vachtsevanos A, Perganta G, Georgalas I. Resistance to antivascular endothelial growth factor treatment in age\u2010related macular degeneration. Drug Des Devel Ther. 2013;7:485\u2013490.","journal-title":"Drug Des Devel Ther"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4095852"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2011-301236"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.12.004"},{"key":"e_1_3_2_29_2","first-page":"2920","article-title":"The alpha\u2010glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth","volume":"55","author":"Pili R","year":"1995","unstructured":"Pili R, Chang J, Partis RA, Mueller RA, Chrest FJ, Passaniti A. The alpha\u2010glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth. Cancer Res. 1995;55:2920\u20132926.","journal-title":"Cancer Res"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041650114"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65733-1"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5388.468"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043091"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.02.007"},{"key":"e_1_3_2_35_2","first-page":"149","article-title":"Angiogenic and angiostatic factors in the molecular control of angiogenesis","volume":"47","author":"Distler JH","year":"2003","unstructured":"Distler JH, Hirth A, Kurowska\u2010Stolarska M, Gay RE, Gay S, Distler O. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 2003;47:149\u2013161.","journal-title":"Q J Nucl Med"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs15-16950"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13089959"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5176"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.221"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80622-4"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.18.4157"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091990105"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19980215)34:3<283::AID-NEU7>3.0.CO;2-Z"},{"key":"e_1_3_2_44_2","first-page":"107","article-title":"Angiogenesis assays using chick chorioallantoic membrane","volume":"46","author":"West DC","year":"2001","unstructured":"West DC, Thompson WD, Sells PG, Burbridge MF. Angiogenesis assays using chick chorioallantoic membrane. Methods Mol Med. 2001;46:107\u2013129.","journal-title":"Methods Mol Med"},{"key":"e_1_3_2_45_2","first-page":"101","article-title":"Oxygen\u2010induced retinopathy in the mouse","volume":"35","author":"Smith LE","year":"1994","unstructured":"Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, D'Amore PA. Oxygen\u2010induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35:101\u2013111.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-009-9155-3"},{"key":"e_1_3_2_47_2","first-page":"H1063","article-title":"Endothelium\u2010dependent, flow\u2010induced dilation of isolated coronary arterioles","volume":"259","author":"Kuo L","year":"1990","unstructured":"Kuo L, Davis MJ, Chilian WM. Endothelium\u2010dependent, flow\u2010induced dilation of isolated coronary arterioles. Am J Physiol. 1990;259:H1063\u2013H1070.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1438"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1224"},{"key":"e_1_3_2_50_2","first-page":"H1558","article-title":"Myogenic activity in isolated subepicardial and subendocardial coronary arterioles","volume":"255","author":"Kuo L","year":"1988","unstructured":"Kuo L, Davis MJ, Chilian WM. Myogenic activity in isolated subepicardial and subendocardial coronary arterioles. Am J Physiol. 1988;255:H1558\u2013H1562.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.301763"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(84)90007-4"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1947"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-23083"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2015.0049"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1089\/pho.2013.3588"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-012-2185-3"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19617"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2013.11.005"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20691"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-16143"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/386671a0"},{"key":"e_1_3_2_63_2","first-page":"23","article-title":"Wound\u2010healing assay","volume":"294","author":"Rodriguez LG","year":"2005","unstructured":"Rodriguez LG, Wu X, Guan JL. Wound\u2010healing assay. Methods Mol Biol. 2005;294:23\u201329.","journal-title":"Methods Mol Biol"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00281-9"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.3.H1054"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17808"},{"key":"e_1_3_2_67_2","first-page":"112","article-title":"Effect of light on oxygen\u2010induced retinopathy in the mouse","volume":"35","author":"Wesolowski E","year":"1994","unstructured":"Wesolowski E, Smith LE. Effect of light on oxygen\u2010induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35:112\u2013119.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.135"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb00157.x"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9613-x"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/380435a0"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/380439a0"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.226423"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-06-291930"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.468199"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303215"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301078"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3176"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05571"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054481"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.119.013673","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:24:16Z","timestamp":1715599456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.119.013673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,19]]},"references-count":79,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2019,11,19]]}},"alternative-id":["10.1161\/JAHA.119.013673"],"URL":"https:\/\/doi.org\/10.1161\/jaha.119.013673","relation":{},"ISSN":["2047-9980"],"issn-type":[{"type":"electronic","value":"2047-9980"}],"subject":[],"published":{"date-parts":[[2019,11,19]]},"assertion":[{"value":"2019-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e013673"}}