Angiopoietin-2: An Emerging Tie to Pathological Vessel Enlargement

Name: Work Video:
Duration: 3 min 30 s
Negar Khosraviani; Ruilin Wu; Jason E. Fish
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'endothelial': [273, 363, 571, 1244, 1631, 1917, 1955, 1990, 2017], 'cell': [274, 1119, 1918], '(EC)': [275], 'behavior.': [276], 'In': [277, 335, 806, 1286], 'case': [279], 'sporadic': [281], 'disease,': [282], 'these': [283, 326, 836, 872, 953], 'typically': [285], 'result': [287, 540], 'somatic': [289, 373, 451, 490, 1518, 1560, 1598], 'within': [291, 1091], 'ECs.': [292, 720, 947], 'The': [293, 439, 548, 700, 1193], 'clonal': [294], 'expansion': [295, 899, 959], 'mutated': [297], 'cells': [298, 366, 574, 1090, 1591, 1632, 2018], 'drives': [299, 696, 1499], 'altered': [300, 1134], 'vessel': [301, 350, 590, 605, 698, 765, 869, 896, 990, 1272, 1914], 'morphology,': [302], 'including': [303, 1258], 'lumen': [304, 898, 958], 'enlargement—a': [305], 'characteristic': [306, 881], 'feature': [307], 'malformed': [309], 'vessels.': [310], 'By': [311], 'identifying': [312], 'mutant': [313], 'characterizing': [316, 515], 'downstream': [317, 517, 1180], 'pathways,': [318], 'novel': [319], 'therapeutic': [320, 385, 597, 1253], 'approaches': [321], 'can': [322, 759, 936, 1104, 1270], 'be': [323, 937, 1030, 1057, 1096, 1207, 1238, 1291, 1310], 'discovered': [324], 'lesions,': [328], 'which': [329, 362, 951, 1196], 'notoriously': [331], 'difficult': [332], 'treat.': [334], 'issue': [337], 'ATVB,': [339], 'Huang': [340, 521, 615, 966, 1166, 1470, 1574, 1608, 2003], 'et': [341, 522, 616, 967, 1167, 1490, 1662, 1734, 1803, 1909, 2052, 2149, 2211], 'al1': [342], 'identify': [343, 533], '(angiopoietin-2)': [345, 1497], 'as': [346, 398, 594, 909, 1228, 1251], 'a': [347, 353, 411, 417, 502, 525, 534, 595, 879, 892, 1058, 1155, 1252, 1337, 1354, 1393, 1665, 1700, 1848, 1877, 2111, 2157], 'regulator': [348], 'enlargement': [351, 788, 827, 991, 1273], 'mouse': [354, 559, 1853, 1878], 'xenograft': [355, 560, 962, 977], 'model': [356, 963, 978, 1879], 'malformation': [359, 815, 1384, 1846], '(CM)': [360], 'colony': [364, 572], 'forming': [365, 573], 'express': [367], 'p.R183Q,': [369], 'common': [372], 'mutation': [374, 453, 470, 491, 1020, 1520, 1561, 1626], 'CM.': [376, 1144, 2177], 'This': [377, 468, 489], 'exciting': [378, 1266], 'discovery': [379], 'opens': [380], 'up': [381], 'new': [382], 'possibilities': [383], 'intervention': [386], 'malformations.See': [389], 'accompanying': [390], 'article': [391, 1426], 'on': [392, 719, 1068, 1740, 1958, 2159], 'page': [393, 1420], 'e27Cutaneous': [394], 'CM,': [395, 1006], 'also': [396, 508, 760, 845, 1095], 'known': [397, 1055, 1186], 'port-wine': [399, 1556], 'stain,': [400], 'affects': [401, 1085], '0.3%': [402], 'infants': [404], 'is': [406, 416, 507, 722, 750, 797, 878, 891, 949, 955, 1037, 1054, 1170, 1185, 1247, 1265, 1325, 1334, 1351, 1390, 1627], 'associated': [407], 'with': [408, 704, 715, 756, 835, 885, 1317, 2156], 'Sturge-Weber': [409, 1553, 1634], 'syndrome,': [410], 'rare': [412], 'neurocutaneous': [413], 'disorder.': [414], 'CM': [415, 564, 1048, 1203, 1278, 1302, 1315], 'slow-flow': [418], 'anomaly': [420], 'characterized': [421, 1227], 'clusters': [423], 'abnormal': [425, 436], 'capillaries': [426], 'venules': [428], 'enlarged,': [431], 'have': [432, 846], 'enhanced': [433], 'sprouting,': [434], 'pericyte': [437, 832, 1079], 'coverage.2': [438], 'occurrence': [440], 'cutaneous': [442], 'brain': [444, 497, 803, 1630, 1773], 'CMs': [445, 500], 'has': [446, 769, 1008, 1024, 1211, 1234], 'been': [447, 770, 1009, 1026, 1212, 1235], 'linked': [448], 'primarily': [449], 'missense': [452, 1519], '(p.': [456], 'R183Q),': [457], 'an': [458, 901, 931, 1229, 1311, 1328, 2020], 'alpha': [459], 'subunit': [460], 'heterotrimeric': [463], 'G': [464, 1985], 'protein': [465], 'complex,': [466], 'Gαq.': [467], 'gain-of-function': [469], 'occurs': [471, 492], 'conserved': [474], 'GTP-binding': [475], 'pocket': [476], 'mediates': [478], 'hydrolysis': [480], 'GTP': [482], 'GDP,': [484], 'resulting': [485, 1809], 'constitutive': [487], 'activity.3': [488], 'predominantly': [493], 'ECs': [495, 993], 'skin': [499], 'at': [501, 1127], 'low': [503], 'allele': [504], 'frequency': [505], 'but': [506, 1014, 1209], 'present': [509], 'some': [511], 'surrounding': [512], 'stromal': [513], 'cells.4,5By': [514], 'pathways': [516, 538, 1179, 1200], 'activated': [519, 654, 685], 'GNAQ,': [520], 'al': [523, 1168], 'reveal': [524, 874], 'critical': [526, 662, 1283], 'role': [527, 903, 1697], 'phospholipase': [529], 'C': [530, 626], 'β3': [531], 'bifurcation': [535], 'activation': [542, 643, 1173, 1982, 1988], 'PKC-NFκB-ANGPT2': [544], 'calcineurin-NFATc1-DSCR1.41': [546], '(Figure).': [547], 'increased': [549], 'expression': [550, 569], 'DSCR1.4': [554], 'were': [555], 'further': [556], 'confirmed': [557], 'studies': [561, 873], 'human': [563, 1772], 'tissues.': [565], 'Importantly,': [566], 'was': [575, 702], 'sufficient': [576], 'induce': [578], 'formation': [580, 1500, 2013], 'enlarged': [582, 928, 1141, 1502], 'CM-like': [583], 'vessels,': [584], 'inhibition': [587, 1269, 1843], 'prevented': [588], 'pathological': [589, 697], 'enlargement,': [591], 'positioning': [592], 'promising': [596], 'target.Download': [598], 'figureDownload': [599], 'PowerPointFigure.': [600], 'drive': [603, 623], 'ANGPT2-dependent': [604, 1124], 'enlargement.': [606, 699], 'Left,': [607], 'Schematic': [608], 'molecular': [611, 921], 'pathway': [612, 1114], 'identified': [613], 'al.': [617, 2212], 'Activating': [618], '(p.R183Q)': [622], 'PLCβ3': [624], '(phospholipase': [625], 'β3)': [627], 'conversion': [630], 'phosphatidylinositol': [632], '4,5-bisphosphate': [633], '(PIP2)': [634], 'inositol': [636], 'phosphate': [637], '(IP3)': [638], 'diacylglyceride': [640], '(DAG).': [641], 'Calcineurin': [642], 'leads': [644, 672], 'nuclear': [647, 675], 'translocation': [648], 'NFATc1': [650], '(nuclear': [651, 679], 'factor': [652, 680], 'T': [655], 'cells-1)': [656], 'induction': [658, 688, 877], 'Down': [660], 'Syndrome': [661], 'region': [663], 'gene': [664, 1060], '1.4': [665], '(DSCR1.4).': [666], 'PKC': [667], '(protein': [668], 'kinase': [669], 'C)': [670], 'translation': [676], 'NFκB': [678], 'κ-light': [681], 'chain': [682], 'enhancer': [683], 'B-cells)': [686], 'Angiopoietin-2': [690, 1842, 2054, 2180], '(ANGPT2).': [691], 'Right,': [692], 'Secretion': [693], 'figure': [701], 'created': [703], 'Biorender.com.Angiopoietins': [705], 'regulate': [706, 1188], 'multiple': [707, 1241, 1256], 'aspects': [708, 1242], 'biology': [711], 'through': [712, 743, 854, 1111, 1220, 1916, 2058], 'their': [713], 'interaction': [714], 'TIE2': [717, 762, 1704, 2059], 'receptor': [718, 1987], 'ANGPT1': [721], 'expressed': [724, 1423], 'adult': [726], 'promotes': [729, 741], 'maturation': [731], 'maintains': [733], 'stability.6,7': [735], 'Conversely,': [736], 'destabilizes': [738], 'vessels': [739, 790, 929, 1142], 'angiogenesis': [742, 2057, 2118], 'antagonism': [744, 1308], 'ANGPT1.6': [746], 'However,': [747], 'action': [749], 'context': [752, 1023], 'dependent': [753, 1067, 2022], 'treatment': [755, 1313], 'mimic': [758], 'activate': [761, 1109], 'mediate': [764], 'enlargement.8': [766], 'Notably,': [767, 1052], 'implicated': [771, 1010], 'pathogenesis': [774, 1204], 'several': [776], 'distinct': [777, 886], 'malformations,': [779], 'where': [780], 'aberrant': [782], 'elevation': [783], 'contributes': [786, 1813], 'morphological': [792], 'changes.': [793], 'For': [794], 'example,': [795], 'elevated': [798], 'patient': [800], 'from': [802, 1099, 1341, 1358, 1366, 1396, 1592, 1810], 'arteriovenous': [804, 1774, 1845, 1875, 2154], 'malformations.9': [805], 'cerebral': [807, 1815, 2153], 'cavernous': [808, 814, 1816], 'malformation,': [809], 'loss': [810], 'CCM3': [812, 1811], '(cerebral': [813], '3)': [816], 'results': [817], 'exocytosis': [819, 1806], 'ANGPT2,': [821], 'contributing': [822], 'disrupted': [824], 'EC': [825, 863, 1041], 'junctions,': [826], 'lumens,': [829], 'defective': [831], 'recruitment.10': [833], 'Consistent': [834], 'observations,': [837], 'EC-specific': [838], 'SMAD4-deficient': [839], 'mice,': [840], 'modeling': [841], 'hereditary': [842, 1850], 'hemorrhagic': [843, 988, 1851], 'telangiectasia,': [844, 989], 'robust': [847], 'elevation.11': [849], 'Inhibition': [850], 'function': [853], 'knockdown': [855], 'or': [856, 944, 1075, 1081, 1157, 1434], 'use': [858], 'inhibitors,': [860], 'restored': [861], 'normal': [862], 'shape': [864, 1919], 'size': [866], 'reduced': [868], 'diameter.11': [870], 'Collectively,': [871], 'unifying': [880], 'malformations': [884, 908, 1219, 1594, 2155], 'causes,': [887], 'potent': [893], 'mediator': [894], 'enlargement.Aberrant': [897], 'plays': [900], 'important': [902, 1292], 'progression': [906], 'it': [910, 1264, 1289], 'significantly': [911], 'alters': [912], 'blood': [913, 1503, 1913], 'flow': [914, 1012, 1959], 'local': [916], 'hemodynamics.': [917], 'Yet,': [918], 'underlying': [920], 'mechanisms': [922], 'responsible': [923], 'development': [926, 1139], 'remains': [930, 1205], 'open': [932], 'question.': [933], 'Expanded': [934], 'lumens': [935], 'increases': [940, 1495], 'number': [943], 'size/morphology': [945], 'It': [948, 1028, 1246], 'unclear': [950], 'processes': [954], 'involved': [956, 1038, 1239], 'used': [964], 'al,': [968], 'although': [969], 'decrease': [971], 'density': [974], 'may': [979, 1131], 'suggest': [980], 'latter.': [982], 'Interestingly,': [983], 'setting': [986, 1046], 'involves': [992], 'becoming': [994], 'larger': [995], 'not': [997, 1025, 1428], 'elongating': [998], 'properly': [999], 'response': [1001, 1922], 'laminar': [1003], 'flow.12,13': [1004], 'Regarding': [1005], 'Gαq': [1007], 'sensing,14,15': [1013], 'impact': [1016], 'R183Q': [1019], 'assessed.': [1027], 'will': [1029, 1290], 'interest': [1032], 'determine': [1034, 1150, 1294], 'whether': [1035, 1071, 1151, 1295, 1306], 'regulating': [1040], 'hemodynamic': [1042], 'responses': [1043], 'other': [1050, 1217, 1280], 'malformations.': [1051], 'flow-responsive': [1059], 'regulates': [1063, 2056], 'phenotypes': [1064, 1303], 'hemodynamics.16': [1069], 'Determining': [1070], 'influences': [1073], 'cell-cell': [1074], 'cell-ECM': [1076], 'adhesion,': [1077], 'modulates': [1078], 'recruitment': [1080], 'if': [1082], 'secretion': [1084], 'phenotype': [1087], 'wild-type': [1089], 'lesion,': [1093], 'should': [1094], 'pursued.': [1097], 'Aside': [1098], 'antagonizing': [1100], 'ANGPT1/TIE2': [1101], 'signaling,': [1102], 'bind': [1105], 'integrins': [1107], 'FAK-RAC1': [1113], 'modulate': [1116], 'cytoskeletal': [1117], 'rearrangements,': [1118], 'migration,': [1120], 'angiogenesis.17,18': [1122], 'Thus,': [1123], 'cytoskeleton': [1125], 'changes': [1126, 1920], 'cellular': [1129], 'level': [1130], 'lead': [1132], 'organization': [1136], 'Further': [1145], 'investigations': [1146], 'needed': [1148], 'acts': [1153, 1297], 'TIE2-dependent': [1156], '-independent': [1158], 'manner': [1159], 'CM.Another': [1161], 'intriguing': [1162], 'aspect': [1163], 'study': [1169], 'concurrent': [1172], 'both': [1175, 1189, 2117], 'angiogenic': [1176, 1197], 'inflammatory': [1178, 1199], 'p.R183Q.1': [1183], 'inflammation': [1190, 1210, 1956], 'angiogenesis.19': [1192], 'extent': [1194], 'contribute': [1201], 'uncovered,': [1208], 'postulated': [1213], 'participate': [1215], 'modulation': [1222], 'microenvironment.20ANGPT2,': [1225], 'initially': [1226], 'antagonistic': [1230], 'ligand': [1231, 1701], 'ANGPT1,': [1233], 'shown': [1236], 'biology.': [1245], 'currently': [1248], 'being': [1249], 'explored': [1250], 'target': [1254], 'diseases,': [1257], 'sepsis': [1259], 'cancer.21': [1261], 'As': [1262], 'such,': [1263], 'prevent': [1271], 'animal': [1275], 'models': [1276], 'malformations—a': [1282], 'disease': [1284], 'phenotype.': [1285], 'future': [1287], 'studies,': [1288], 'initiate': [1299], 'maintain': [1301], 'elucidate': [1305], 'would': [1309], 'effective': [1312], 'patients': [1316], 'established': [1318], 'pathologies.Article': [1320], 'InformationSources': [1321], 'FundingN.': [1323], 'supported': [1326, 1335, 1352, 1391], 'Ontario': [1329, 1380], 'Graduate': [1330, 1339], 'Studentship.': [1331], 'R.': [1332, 1374, 1410], 'Scholarship': [1340], 'Canadian': [1343], 'Institutes': [1344], '(CIHR).': [1348], 'J.E.': [1349], 'Chair': [1357], 'CIHR': [1359, 1397], 'his': [1361], 'lab': [1362], 'received': [1363], 'infrastructure': [1364], 'funding': [1365], 'Foundation': [1369], 'Innovation,': [1371], 'John': [1373], 'Evans': [1375], 'Leaders': [1376], 'Fund': [1377], 'Fund.': [1382], 'research': [1385], 'laboratory': [1389], 'Project': [1394], 'Grant': [1395], '(PJT': [1398], '155922)': [1399], 'US': [1402], 'Defense': [1405], '(W81XWH-18-1-0351).Disclosures': [1406], 'None.Footnotes*N.': [1407], 'contributed': [1412], 'equally.For': [1413], 'Sources': [1414], 'Funding': [1416], 'Disclosures,': [1418], 'see': [1419], '5.The': [1421], 'opinions': [1422], 'necessarily': [1429], 'those': [1430], 'editors': [1433], 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'KeywordsEditorialsangiopoietin-2capillary': [2236], 'malformationsomatic': [2237], 'mutationGNAQvessel': [2238], 'enlargementPDF': [2239], 'download': [2240], 'Advertisement': [2241]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W4226317957', 'counts_by_year': [{'year': 2024, 'cited_by_count': 3}, {'year': 2023, 'cited_by_count': 1}], 'updated_date': '2024-12-16T01:23:56.376612', 'created_date': '2022-05-05'}
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