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'2021https://doi.org/10.1161/CIRCULATIONAHA.120.052975Circulation.': [567], '2021;144:662–665Genome-wide': [568], 'association': [569, 580, 1756, 1844, 2128], 'studies': [570, 1757, 1759, 2129], 'have': [571], 'led': [572], 'identification': [574, 1794], '>160': [576], 'variants': [577, 589], 'with': [578, 624, 644, 716, 862, 1002, 1028, 1187, 1205, 1266, 1470, 1481, 1543, 1564, 1750, 1872], 'significant': [579], 'coronary': [582, 1267, 1751, 2131, 2186], 'artery': [583, 1268, 1752, 1935, 2132, 2187], 'disease': [584, 646, 1753], '(CAD).1': [585], 'One': [586], 'identified': [590, 633, 893, 1841], '(rs7678555)': [591], 'is': [592, 701, 711, 731, 944, 1084, 1334, 1802, 1831, 1870], 'located': [593, 732, 946], 'on': [594, 683, 1039, 1097, 1239, 1771, 2034, 2178], 'chromosome': [595], 'proximity': [598], 'linked': [602, 1803], 'enhanced': [604, 1074, 1866, 2290], 'mRNA': [606, 1219, 1520, 1699], 'levels': [607, 1220, 1700, 1891], 'aorta.2': [609], 'The': [610, 668, 690, 729, 989, 1277, 1309, 1351, 1615, 2051], 'mechanisms': [611], 'by': [612, 634, 658, 703, 837, 1221, 1703, 1754, 1786, 1842, 1945], 'which': [613, 700, 1247], 'variant': [615, 638, 730, 751, 803, 847, 891, 943, 1038, 1071, 1096, 1265, 1368, 1527, 1797], 'affects': [616], 'CAD': [617, 629, 717, 727, 1805, 1835, 1908], 'risk': [618, 1281, 1836, 1874, 2224], 'remain': [619, 1928], 'unclear.In': [620], 'extended': [622, 1273, 1761, 1808], 'family': [623, 1034, 1327], 'high': [625], 'prevalence': [626, 1278], 'premature': [628], '(Figure': [630, 768, 866, 906, 1007, 1062, 1146, 1195, 1226, 1909], '[A]),': [631], 'we': [632, 773, 784, 830, 843, 858, 877, 953, 1018, 1103], 'exome': [635, 1324], 'sequencing': [636, 924], 'locus': [642, 1372, 1589, 1840], 'cosegregating': [643], '(ie,': [647], 'NM_033430.3:c.19A>T': [648], '[p.Lys7Ter;': [649], 'gnomAD:': [650], '4-120548312-T-A,': [651], 'MAF': [652], '2.1·10−4]).': [653], 'Study': [654], 'approval': [655], 'was': [656, 719, 915, 1134, 1283, 1355, 1464, 1577, 1618, 1628, 1943], 'obtained': [657], 'institutional': [660], 'ethics': [661], 'committee;': [662], 'participating': [663], 'individuals': [664, 1561], 'gave': [665], 'informed': [666], 'consent.': [667], 'data': [669, 1067, 1231], 'that': [670, 710, 845, 968, 1069, 1082, 1109, 1801, 1829], 'support': [671], 'findings': [673], 'this': [675, 782], 'study': [676, 1090], 'are': [677, 1688, 1725, 2031], 'available': [678, 1033, 1043, 1560], 'from': [679, 1989, 2020], 'corresponding': [681], 'authors': [682, 2053], 'reasonable': [684], 'request.': [685], 'encodes': [687], 'phosphodiesterase': [688, 2249], '5A.': [689], 'enzyme': [691, 709], 'degrades': [692], 'second': [694, 1414, 1422, 1765, 1857], 'messenger': [695, 1766, 1858], 'cyclic': [696, 1439, 2247], 'guanosine': [697, 1440, 1937], 'monophosphate': [698, 1441], '(cGMP),': [699], 'produced': [702], 'soluble': [705, 815, 825, 1449, 1739], 'guanylyl': [706, 816, 826, 1450, 1740], 'cyclase,': [707], 'also': [712, 819], 'genome-wide': [713, 1755, 1843, 2127], 'significantly': [714], 'associated': [715, 1749, 1871], 'found': [720, 844, 1746], 'be': [722, 1748, 1784, 1930], 'mutated': [723, 972, 1055, 1117, 1412], 'large': [726], 'family.3': [728], 'first': [735, 744, 774], 'intron': [736], 'isoforms': [738], 'PDE5A1': [739], 'PDE5A3': [741], 'exon': [745], 'PDE5A2.': [747], 'In': [748, 1042, 1119, 1911], 'PDE5A2,': [749, 834], 'leads': [752, 1072], 'exchange': [755], 'lysine': [757], 'stop': [760], 'codon': [761], 'seventh': [764], 'amino': [765], 'acid': [766, 898], 'position': [767], '[B]': [769], '[C]).': [771], 'Thus,': [772], 'assumed': [775], 'loss': [777, 853], 'PDE5A2': [779, 788, 855, 936, 959, 1025, 1080, 1101, 1158, 1218, 1240, 1380, 1393, 1398, 1519, 1658, 1799, 1811], 'activity.': [780], 'To': [781, 870, 1089, 1400], 'end,': [783], 'cloned': [785], 'coding': [787], 'wild-type': [789, 970, 1004, 1030, 1058, 1114, 1168, 1185, 1347], 'sequence': [790, 1500], 'into': [791], 'expression': [793, 1021, 1075, 1201, 1241, 1800], 'vector': [794], 'containing': [795, 991, 1495], 'C-terminal': [797], 'V5-tag': [798], 'introduced': [800], 'p.Lys7Ter': [802, 890, 993, 1024, 1095, 1255, 1410, 1505, 1526, 1555], 'using': [804, 828, 966, 1162, 1202, 1427, 1533, 1633], 'vitro': [806, 881, 1429], 'mutagenesis.': [807], 'We': [808, 961, 1197], 'used': [809], 'HEK': [810, 1444], '293': [811, 1445], 'cells': [812, 1214, 1386, 1446, 1714, 1774], 'stably': [813], 'overexpressing': [814, 1387, 1447], 'cyclase': [817, 827, 1451, 1741], 'overexpress': [820], 'PDE5A2p.Lys7Ter.': [821], 'After': [822], 'activation': [823], 'S-nitrosoglutathione,': [829], 'unexpectedly': [831], 'observed': [832, 1216], 'active': [833], 'as': [835, 900, 1284, 1336, 2013, 2015], 'demonstrated': [836], 'reduced': [838, 863, 1873], 'cGMP': [839, 1462, 1767, 1859, 1890], 'levels.': [840], 'Using': [841, 1009], 'immunoblotting,': [842], 'did': [848, 931], 'not': [849, 921, 932, 939], 'lead': [850], 'protein;': [856], 'rather,': [857], 'detected': [859, 1061], 'band': [861], 'protein': [864], 'size': [865], '[D]': [867], '[E]).': [869], 'identify': [871, 1401], 'putative': [872], 'alternative': [873, 902, 911, 934, 949, 973, 994, 1005, 1157, 1402, 1498, 1659], 'starts': [874, 1403], 'translation,': [876, 1405], 'performed': [878, 962], 'serial': [879], 'mutagenesis': [882, 1432], 'methionine': [885, 896, 1415, 1419, 1425], 'residues': [886], 'downstream': [887, 1408], 'third': [895, 1418, 1424], '(amino': [897], '92)': [899], 'start': [903, 912], 'translation': [905, 914], '[D]).': [907], 'Of': [908], 'note,': [909], 'previously': [916], 'described': [917], 'PDE3A4': [919], 'but': [920], 'PDE5A.': [922], 'RNA': [923, 1046, 1203], '3': [926, 1049], 'carriers': [927, 1251], 'matched': [929], 'controls': [930], 'reveal': [933], 'spliced': [935], 'transcripts': [937], '(data': [938], 'shown).': [940], 'Because': [941], 'furthermore': [945], 'promoter': [951, 974, 995, 1006, 1122, 1159, 1499, 1660], 'region,': [952], 'next': [954, 1198], 'investigated': [955], 'whether': [956], 'it': [957, 1847], 'influences': [958], 'expression.': [960], 'reporter': [963, 998], 'gene': [964, 999, 1491, 1833], 'assays': [965], 'constructs': [967], 'contained': [969], 'sequences': [975, 1661], '(±300': [976], 'nucleotides': [977], '3′': [978], '5′': [980], 'variant)': [983], 'upstream': [984], 'firefly': [987], 'luciferase.': [988], 'construct': [990], 'displayed': [996, 1335], 'increased': [997, 1020, 1217, 1709, 1893], 'activity': [1000], 'compared': [1001, 1027, 1186, 1563], '[F]).': [1008], 'droplet': [1010, 1534], 'digital': [1011, 1535], 'polymerase': [1012, 1223, 1536, 1705], 'chain': [1013, 1224, 1537, 1706], 'reaction': [1014, 1225, 1538], 'allele-specific': [1016, 1540], 'probes,': [1017], 'validated': [1019], 'allele': [1026, 1031, 1059, 1172, 1190, 1556, 1567], 'members': [1035, 1328], 'carrying': [1036, 1165, 1608], '1': [1040], 'allele.': [1041, 1118, 1614], 'whole': [1044, 1522], 'blood': [1045, 1523], 'samples': [1047], 'carriers,': [1050], 'more': [1051], 'copies': [1052], 'than': [1056], 'were': [1060, 1329, 1411, 1487, 1513, 1531, 1557, 1685, 1708, 1722, 1745], '[G]).': [1063], 'Taken': [1064, 1228], 'together,': [1065, 1229], 'these': [1066, 1230], 'indicate': [1068], 'N-terminally': [1078], 'truncated': [1079], 'isoform': [1081], 'still': [1083], 'capable': [1085], 'degrading': [1087], 'cGMP.': [1088], 'effect': [1092, 1236], 'regulation': [1099], 'expression,': [1102], 'aimed': [1104], 'identifying': [1106], 'transcription': [1107, 1127, 1602], 'factors': [1108, 1282], 'specifically': [1110], 'bind': [1111, 1137], 'or': [1115, 1169, 1338, 1346, 1455, 1504, 1612, 1668, 1895, 1905], 'eukaryotic': [1121], 'database,': [1123], 'zinc': [1125], 'finger': [1126], 'factor': [1128, 1603], 'ZFX': [1129, 1154, 1182, 1200, 1238, 1581, 1604, 1626], '(Zinc': [1130], 'Finger': [1131], 'Protein': [1132], 'X-linked)': [1133], 'predicted': [1135], 'several': [1139], 'sites': [1140, 1583], 'within': [1141], 'region': [1143], 'interest': [1145], '[H]).': [1147], 'Chromatin': [1148, 1644], 'immunoprecipitation': [1149, 1645, 1663, 1677], 'experiments': [1150, 1473, 1508, 1680, 1717], 'confirmed': [1151, 1629], 'binding': [1152, 1180, 1545, 1582, 1599, 1627], 'region.': [1160], 'Pull-downs': [1161], 'oligonucleotide': [1163, 1541, 1606], 'baits': [1164, 1607], 'either': [1166, 1609, 1665], 'mutant': [1171, 1189, 1254, 1397, 1613], 'HeLa': [1174, 1622, 1651], 'cell': [1175], 'nuclear': [1176, 1623], 'lysates': [1177], 'revealed': [1178], 'preferential': [1179], 'western': [1192, 1631], 'blot': [1193, 1632], 'analysis': [1194, 1478], '[I–K]).': [1196], 'silenced': [1199], 'interference': [1204], 'specific': [1206], 'small': [1207], 'interfering': [1208], 'RNAs': [1209], 'vascular': [1211, 1243, 1711], 'smooth': [1212, 1244, 1712, 1772], 'muscle': [1213, 1245, 1713, 1773], 'quantitative': [1222, 1704], '[L]).': [1227], 'point': [1232], 'repressive': [1235], 'cells,': [1246], 'seems': [1248], 'altered': [1249], 'allele.Download': [1256], 'figureDownload': [1257], 'PowerPointFigure.': [1258], 'Association': [1259, 2175], '(phosphodiesterase': [1263], '5A)': [1264], 'disease/myocardial': [1269], 'infarction': [1270], 'family.A,': [1274], 'pedigree.': [1276], 'traditional': [1280], 'follows:': [1285], 'diabetes,': [1286], '0%;': [1287], 'hypertension,': [1288], '39%;': [1289], 'low-density': [1290], 'lipoprotein': [1291], 'cholesterol': [1292], 'level,': [1293], 'median': [1294], '143': [1295], 'mg/dL': [1296], '(interquartile': [1297], 'range,': [1298], '126.3–176.3': [1299], 'mg/dL);': [1300], 'body': [1302], 'mass': [1303], 'index,': [1304], '23.8': [1305], 'kg/m2': [1306], '(range,': [1307], '21.9–25.3).': [1308], 'arrow': [1310], 'denotes': [1311], 'index': [1313, 1321], 'patient': [1314, 1322], '(III-1).': [1315], 'Individuals': [1316], 'III-6,': [1317], 'III-23,': [1318], 'underwent': [1323], 'sequencing.': [1325], 'Other': [1326], 'genotyped.': [1330], 'carrier': [1332, 1344], 'status': [1333, 1345], '+/–': [1337], '–/–': [1339], 'case': [1341], 'heterozygous': [1343, 1525], '(WT)': [1348], 'PDE5A,': [1349], 'respectively.': [1350], 'maximum': [1352], 'LOD': [1353], 'score': [1354], '3.16': [1356], 'recombination': [1359], 'fraction': [1360], 'θ=0.17.': [1361], 'B': [1362], 'C,': [1364, 2207], 'Location': [1365], '(B)': [1373], 'secondary': [1377], 'structure': [1378], '(C).': [1381], 'D,': [1382, 2204, 2211, 2266, 2278], 'Immunoblot': [1383], 'HEK293': [1385], '(pDEST40;': [1388], 'Thermo': [1389], 'Fisher': [1390, 1434], 'Scientific)': [1391], 'WT': [1392, 1503, 1566, 1611], '(PDE5A2WT)': [1394], '(PDE5A2p.Lys7Ter).': [1399], '2': [1406], 'methionines': [1407], '(ΔMet2:': [1413], 'mutated;': [1416, 1420], 'ΔMet3:': [1417], 'ΔMet2/3:': [1421], 'mutated)': [1426], 'Quik': [1430], 'Change': [1431], '(Thermo': [1433], 'Scientific).': [1435], 'E,': [1436, 2154], 'Levels': [1437], '(cGMP)': [1442], 'PDE5A2WT,': [1453], 'PDE5A2p.Lys7Ter,': [1454], 'control': [1456, 1669], '(no': [1457], 'PDE5A).': [1458], 'Radioimmunoassay': [1459], 'determine': [1461], 'formation': [1463, 1780], 'analyzed': [1465], 'after': [1466, 1646, 1662, 2042], '60': [1467], 'seconds': [1468], 'stimulation': [1469], 'S-nitrosoglutathione.': [1471], 'Nine': [1472], '1-way': [1475], 'repeated': [1476], 'measures': [1477], 'variance': [1480], 'Tukey': [1483], 'multiple': [1484], 'comparisons': [1485], 'test': [1486, 1512, 1576, 1684, 1721], 'performed.': [1488, 1514, 1578, 1686, 1723], 'F,': [1489, 2240], 'Reporter': [1490], 'assay': [1492], '(pGL4.10;': [1493], 'Promega)': [1494], 'alleles.': [1506], 'Five': [1507, 1679, 1716], 'paired': [1510, 1682, 1719], 't': [1511, 1575, 1683, 1720], 'G,': [1515], 'Copy': [1516, 1529, 1551], 'numbers': [1517, 1530, 1552], 'carriers.': [1528], 'determined': [1532, 1702], 'primers': [1542], 'equal': [1544], 'affinity': [1546], 'both': [1548], 'alleles': [1549], '(Bio-Rad).': [1550], 'higher': [1558], '(n=3)': [1562], '(133.5±2.8': [1568], 'vs': [1569], '116.7±3.4': [1570], '[copies/µL],': [1571], 'respectively;': [1572], 'P=0.01).': [1573], 'Paired': [1574], 'H,': [1579], 'Predicted': [1580], '(red': [1584], 'boxes)': [1585], '(https://epd.epfl.ch/cgi-bin/get_doc?db=hgEpdNew&format=genome&entry=PDE5A_2;': [1590], 'accessed': [1591], 'November': [1592], '23,': [1593, 2323], '2020;': [1594], 'cutoff': [1595], 'P=0.001).': [1596], 'I,': [1597, 2158], 'Differential': [1598], 'pull-down': [1616], 'experiment': [1617], 'carried': [1619], 'out': [1620], 'lysate': [1624], 'anti-ZFX': [1635], 'antibody': [1636], '(5419S;': [1637], 'Cell': [1638], 'Signaling': [1639], 'Technology).': [1640], 'J': [1641], 'K,': [1643, 1673, 2198, 2276], 'overexpression': [1647], 'ZFX-V5': [1649], 'cells.': [1652], 'J,': [1653, 2116, 2196, 2234, 2238], 'Agarose': [1654], 'gel': [1655], 'electrophoresis': [1656], 'V5': [1666], '(αV5)': [1667], '(immunoglobulin': [1670], 'G': [1671], '[IgG]).': [1672], 'Quantification': [1674], 'chromatin': [1676], 'experiments.': [1678], 'Data': [1687, 1724], 'mean': [1689, 1726], 'SEM.': [1691, 1728], 'L,': [1692, 2121, 2156], 'Secondary': [1693], 'silencing': [1695], 'ZFX,': [1697], '(as': [1701], 'reaction)': [1707], '(PromoCell).': [1715], 'M,': [1729, 2215, 2274], 'Translational': [1730], 'perspective:': [1731], 'genes': [1732], 'encoding': [1733], 'α1': [1735], 'subunit': [1736], '(sGC)': [1742], 'families.': [1762], 'Whereas': [1763, 1862], 'has': [1768, 1881, 1985], 'inhibitory': [1769], 'effects': [1770], 'platelets,': [1776], 'example,': [1778], 'its': [1779], 'degradation': [1782, 1897], 'can': [1783], 'modulated': [1785], 'sGC': [1787], 'stimulators': [1788], 'inhibitors,': [1791], 'respectively.We': [1792], 'report': [1793, 2054], 'affecting': [1798], 'family.': [1809], 'This': [1810, 1824], 'gain-of-function': [1812], 'mutation': [1813], 'adds': [1814], 'short': [1817], 'list': [1818], 'monogenic': [1820], 'forms': [1821], 'CAD.': [1823], 'finding': [1825], 'strengthens': [1826], 'assumption': [1828], 'mediating': [1834], 'studies.2': [1845], 'Furthermore,': [1846], 'highlights': [1848], 'importance': [1850], 'nitric': [1852, 1867, 1878, 2220, 2291], 'oxide': [1853, 1868, 1879, 2221, 2292], 'signaling': [1854, 1869, 1880], 'atherosclerosis.': [1861], 'genetic': [1863, 2287], 'predisposition': [1864, 2288], 'CAD,5': [1876], 'dysfunctional': [1877], 'been': [1882], 'shown': [1883], 'increase': [1885], 'risk.3': [1886], 'Pharmacologic': [1887], 'elevation': [1888], 'via': [1892], 'production': [1894], 'decreased': [1896], 'might': [1898], 'represent': [1899], 'promising': [1901], 'strategy': [1902], 'prevention': [1904, 2039], 'treatment': [1906], '[M]).': [1910], 'clinical': [1913], 'setting,': [1914], 'mechanistic': [1916], 'role': [1917], 'therapeutic': [1920], 'potential': [1921], 'targeting': [1923], 'particularly': [1924], 'atherosclerosis': [1927], 'investigated.Nonstandard': [1931], 'Abbreviations': [1932], 'AcronymsCADcoronary': [1934], 'diseasecGMPcyclic': [1936], 'monophosphatePDE5Aphosphodiesterase': [1938], '5ASources': [1939], 'FundingThis': [1941], 'work': [1942], 'supported': [1944], 'Deutsche': [1946], 'Forschungsgemeinschaft': [1947], '(SFB1123,': [1948], 'B02),': [1949], 'Corona': [1951], 'Foundation,': [1952], 'Fondation': [1954], 'Leducq': [1955], '(CADgenomics,': [1956], '12CVD02),': [1957], 'Federal': [1960], 'Ministry': [1961], 'Education': [1963], '(e:AtheroSysMed,': [1966], '01ZX1313A-2014),': [1967], 'European': [1969], 'Union': [1970], 'Seventh': [1971], 'Framework': [1972], 'Program': [1973], 'FP7/2007': [1974], '2013': [1976], '(CVgenes-at-target,': [1977], 'HEALTH-F2-2013-601456),': [1978], 'ERA-CVD': [1980], '(Druggable-MI-genes,': [1981], '01KL1802).Disclosures': [1982], 'Dr': [1983, 2026, 2029], 'received': [1986], 'personal': [1987, 2018], 'fees': [1988, 2019], 'MSD': [1990], 'Sharp': [1991], '&': [1992], 'Dohme,': [1993], 'Amgen,': [1994], 'Bayer': [1995], 'Vital': [1996], 'GmbH,': [1997], 'Boehringer': [1998], 'Ingelheim,': [1999], 'Daiichi-Sankyo,': [2000], 'Novartis,': [2001], 'Servier,': [2002], 'Brahms,': [2003], 'Bristol-Myers-Squibb,': [2004], 'Medtronic,': [2005], 'Sanofi': [2006], 'Aventis,': [2007], 'Synlab,': [2008], 'Pfizer,': [2009], 'Vifor': [2011], 'T': [2012, 2059], 'well': [2014], 'grants': [2016], 'AstraZeneca': [2021], 'outside': [2022, 2047], 'submitted': [2024, 2049], 'work.': [2025, 2050], 'named': [2032], 'inventors': [2033], 'patent': [2036], 'application': [2037], 'restenosis': [2041], 'angioplasty': [2043], 'stent': [2045], 'implantation': [2046], 'other': [2052], 'no': [2055], 'conflicts.Footnoteshttps://www.ahajournals.org/journal/circ*T.A.': [2056], 'contributed': [2061], 'equally.For': [2062], 'Sources': [2063], 'Funding': [2065], 'Disclosures,': [2067], 'see': [2068], 'page': [2069], '664.Correspondence': [2070], 'protected]mhn.deThorsten': [2093], 'thorsten.[email': [2113], 'protected]deReferences1.': 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'publishedAugust': [2322], 'Keywordsatherosclerosisphosphodiesterase': [2325], '5Amyocardial': [2326], 'infarctionnitric': [2327], 'oxidegeneticsPDF': [2328], 'download': [2329], 'SubjectsGene': [2330], 'Expression': [2331], 'RegulationGeneticsVascular': [2333], 'BiologyBasic': [2334], 'Science': [2335], 'ResearchCoronary': [2336]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W3194560366', 'counts_by_year': [{'year': 2024, 'cited_by_count': 4}, {'year': 2023, 'cited_by_count': 1}, {'year': 2022, 'cited_by_count': 3}, {'year': 2021, 'cited_by_count': 1}], 'updated_date': '2024-09-12T07:15:36.028681', 'created_date': '2021-08-30'}