0 9 PPARalpha PPARalpha NNP 10 20 activators activator NNS 21 28 inhibit inhibit VBP 29 45 cytokine-induced cytokine-induced JJ 46 54 vascular vascular JJ 55 59 cell cell NN 60 68 adhesion adhesion NN 69 79 molecule-1 molecule-1 NN 80 90 expression expression NN 91 93 in in IN 94 99 human human JJ 100 111 endothelial endothelial JJ 112 117 cells cell NNS 117 118 . . . 120 130 BACKGROUND background NN 130 131 : : : 132 140 Adhesion Adhesion NNP 141 149 molecule molecule NN 150 160 expression expression NN 161 163 on on IN 164 167 the the DT 168 179 endothelial endothelial JJ 180 184 cell cell NN 185 186 ( ( ( 186 188 EC EC NNP 188 189 ) ) ) 190 197 surface surface NN 198 200 is be VBZ 201 209 critical critical JJ 210 213 for for IN 214 223 leukocyte leukocyte NN 224 235 recruitment recruitment NN 236 238 to to TO 239 254 atherosclerotic atherosclerotic JJ 255 262 lesions lesion NNS 262 263 . . . 264 270 Better good JJR 271 284 understanding understanding NN 285 287 of of IN 288 303 transcriptional transcriptional JJ 304 314 regulation regulation NN 315 317 of of IN 318 326 adhesion adhesion NN 327 336 molecules molecule NNS 337 339 in in IN 340 343 ECs ec NNS 344 347 may may MD 348 355 provide provide VB 356 365 important important JJ 366 373 insight insight NN 374 378 into into IN 379 385 plaque plaque NN 386 395 formation formation NN 395 396 . . . 397 407 Peroxisome Peroxisome NNP 408 430 proliferator-activated proliferator-activated JJ 431 445 receptor-alpha receptor-alpha NN 446 447 ( ( ( 447 456 PPARalpha PPARalpha NNP 456 457 ) ) ) 457 458 , , , 459 460 a a DT 461 467 member member NN 468 470 of of IN 471 474 the the DT 475 482 nuclear nuclear JJ 483 491 receptor receptor NN 492 498 family family NN 498 499 , , , 500 509 regulates regulate VBZ 510 514 gene gene NN 515 525 expression expression NN 526 528 in in IN 529 537 response response NN 538 540 to to TO 541 548 certain certain JJ 549 554 fatty fatty JJ 555 560 acids acid NNS 561 564 and and CC 565 571 fibric fibric JJ 572 576 acid acid NN 577 588 derivatives derivative NNS 588 589 . . . 590 593 The the DT 594 601 present present JJ 602 607 study study NN 608 620 investigated investigate VBD 621 630 PPARalpha PPARalpha NNP 631 641 expression expression NN 642 644 in in IN 645 650 human human JJ 651 654 ECs ec NNS 655 658 and and CC 659 664 their their PRP$ 665 675 regulation regulation NN 676 678 of of IN 679 687 vascular vascular JJ 688 692 cell cell NN 693 701 adhesion adhesion NN 702 712 molecule-1 molecule-1 NN 713 714 ( ( ( 714 720 VCAM-1 vcam-1 NN 720 721 ) ) ) 721 722 . . . 723 730 METHODS methods NNS 731 734 AND and CC 735 742 RESULTS results NNS 742 743 : : : 744 764 Immunohistochemistry Immunohistochemistry NNP 765 773 revealed reveal VBD 774 778 that that IN 779 784 human human JJ 785 792 carotid carotid JJ 793 799 artery artery NN 800 803 ECs ec NNS 804 811 express express VBP 812 821 PPARalpha PPARalpha NNP 821 822 . . . 823 835 Pretreatment Pretreatment NNP 836 838 of of IN 839 847 cultured culture VBN 848 853 human human JJ 854 857 ECs ec NNS 858 862 with with IN 863 866 the the DT 867 876 PPARalpha PPARalpha NNP 877 887 activators activator NNS 888 899 fenofibrate fenofibrate NN 900 902 or or CC 903 910 WY14643 WY14643 NNP 911 920 inhibited inhibit VBD 921 938 TNF-alpha-induced tnf-alpha-induced JJ 939 945 VCAM-1 vcam-1 NN 946 948 in in IN 949 950 a a DT 951 956 time- time- NN 957 960 and and CC 961 984 concentration-dependent concentration-dependent JJ 985 991 manner manner NN 991 992 , , , 993 995 an an DT 996 1002 effect effect NN 1003 1006 not not RB 1007 1011 seen see VBN 1012 1016 with with IN 1017 1026 PPARgamma PPARgamma NNP 1027 1037 activators activator NNS 1037 1038 . . . 1039 1043 Both both DT 1044 1053 PPARalpha PPARalpha NNP 1054 1064 activators activator NNS 1065 1074 decreased decrease VBD 1075 1091 cytokine-induced cytokine-induced JJ 1092 1098 VCAM-1 vcam-1 NN 1099 1103 mRNA mrna NN 1104 1114 expression expression NN 1115 1122 without without IN 1123 1131 altering alter VBG 1132 1135 its its PRP$ 1136 1140 mRNA mrna NN 1141 1150 half-life half-life NN 1150 1151 . . . 1152 1161 Transient transient JJ 1162 1174 transfection transfection NN 1175 1177 of of IN 1178 1188 deletional deletional JJ 1189 1195 VCAM-1 vcam-1 NN 1196 1204 promoter promoter NN 1205 1215 constructs construct NNS 1216 1219 and and CC 1220 1235 electrophoretic electrophoretic JJ 1236 1244 mobility mobility NN 1245 1250 shift shift NN 1251 1257 assays assay NNS 1258 1265 suggest suggest VBP 1266 1270 that that IN 1271 1282 fenofibrate fenofibrate NN 1283 1291 inhibits inhibit VBZ 1292 1298 VCAM-1 vcam-1 NN 1299 1312 transcription transcription NN 1313 1315 in in IN 1316 1320 part part NN 1321 1323 by by IN 1324 1334 inhibiting inhibit VBG 1335 1344 NF-kappaB nf-kappab NN 1344 1345 . . . 1346 1353 Finally finally RB 1353 1354 , , , 1355 1364 PPARalpha PPARalpha NNP 1365 1375 activators activator NNS 1376 1389 significantly significantly RB 1390 1397 reduced reduce VBD 1398 1406 adhesion adhesion NN 1407 1409 of of IN 1410 1414 U937 u937 NN 1415 1420 cells cell NNS 1421 1423 to to TO 1424 1432 cultured culture VBN 1433 1438 human human JJ 1439 1442 ECs ec NNS 1442 1443 . . . 1444 1455 CONCLUSIONS conclusions NNS 1455 1456 : : : 1457 1462 Human human JJ 1463 1466 ECs EC NNPS 1467 1474 express express VBP 1475 1484 PPARalpha PPARalpha NNP 1484 1485 , , , 1486 1487 a a DT 1488 1499 potentially potentially RB 1500 1509 important important JJ 1510 1519 regulator regulator NN 1520 1522 of of IN 1523 1536 atherogenesis atherogenesis NN 1537 1544 through through IN 1545 1548 its its PRP$ 1549 1564 transcriptional transcriptional JJ 1565 1572 control control NN 1573 1575 of of IN 1576 1582 VCAM-1 vcam-1 NN 1583 1587 gene gene NN 1588 1598 expression expression NN 1598 1599 . . . 1600 1604 Such such JJ 1605 1613 findings finding NNS 1614 1618 also also RB 1619 1623 have have VBP 1624 1636 implications implication NNS 1637 1646 regarding regard VBG 1647 1650 the the DT 1651 1659 clinical clinical JJ 1660 1663 use use NN 1664 1666 of of IN 1667 1681 lipid-lowering lipid-lowering JJ 1682 1688 agents agent NNS 1688 1689 , , , 1690 1694 like like IN 1695 1701 fibric fibric JJ 1702 1707 acids acid NNS 1707 1708 , , , 1709 1714 which which WDT 1715 1718 can can MD 1719 1727 activate activate VB 1728 1737 PPARalpha PPARalpha NNP 1737 1738 . . .