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Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders?

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(1)Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders? Plaisier, G.M.. Citation Plaisier, G. M. (2008, May 7). Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders?. Retrieved from https://hdl.handle.net/1887/12861 Version:. Corrected Publisher’s Version. License:. Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded from:. https://hdl.handle.net/1887/12861. Note: To cite this publication please use the final published version (if applicable)..

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(9) 5BCMF. First-trimester decidual mRNA expression of angiogenic factors (in ng/ μl). N3/"DPOUFOU NFBO‘4&. a "OHJPHFOJD'BDUPS. '(3 O. 'PMEJOEVDUJPO NFBO‘4&. b 1& O. '(3 O. 1& O. 7&('". 0.1 ± 0.0. 0.1 ± 0.0. 53 ± 46. 2±1. 1M('. 4.1 ± 1.8. 8.2 ± 3.1. 33 ± 21. 35 ± 24. ,%3. 0.7 ± 0.3. 1.7 ± 0.8. 26 ± 17. 13 ± 8. 'MU. 0.6 ± 0.2. 2.0 ± 1.3. 2±1. 3±2. "OH. 0.02 ± 0.0. 0.4 ± 0.4. 59 ± 34. 29 ± 21. "OH. 0.4 ± 0.2. 3.6 ± 2.0. 8±4. 5±3. 5*&. 0.9 ± 0.8. 19.6 ± 19.5. 37 ± 30. 68 ± 47. $IBQUFS. 'JSTUUSJNFTUFSEFDJEVBMN3/"FYQSFTTJPOXBTEFUFSNJOFECZ351$3BOEDPNQBSFECFUXFFOQSFHOBODJFT SFTVMUJOH JO '(3 PS 1& BOE UIFJS NBUDIFE DPOUSPMT 5IF °SFQFBUFE NFBTVSFT "/07"± XBT QFSGPSNFE UP BOBMZTFUIFEBUB B N3/"DPOUFOUXBTFYQSFTTFEJODZDMFUISFTIPME $U .FBO$UQFSHFOF("1%) 7&('" 1M('  ,%3 'MU "OH "OH BOE5*&$ZDMFUISFTIPMEXFSFDPOWFSUFEJOUPOHμM VTJOHBTUBOEBSEDVSWFPGUPUBM3/"7BMVFTXFSFDPSSFDUFEGPSN3/"JOQVUCZDBMDVMBUJOHUIFSBUJP OHμM UBSHFUHFOF.  OHμM ("1%). BOEUIFTFWBMVFTBSFFYQSFTTFEBT®N3/"DPOUFOU¯JOUIFUBCMF C 'PMEJOEVDUJPOJODBTFTDPNQBSFEUPDPOUSPMTXBTDBMDVMBUFEBTUIFSBUJPOHμM DBTF OHμM DPOUSPMT . . %*4$644*0/ 5IFSFTVMUTTIPXFEUIBU¹STUUSJNFTUFSEFDJEVBMUJTTVFTPCUBJOFEGSPNDIPSJPOJDWJMMPVT TBNQMJOH FYQSFTTFE BMM FYBNJOFE BOHJPHFOJD GBDUPST N3/" MFWFMT PG 7&('"  1M('  ,%3 "OH "OHBOE5*&BQQFBSFEVOSFHVMBUFEJO'(3DBTFTDPNQBSFEUPNBUDIFE DPOUSPMT*OBEEJUJPO 1M(' "OHBOE5*&N3/"BQQFBSFEVOSFHVMBUFEJO1&DBTFT DPNQBSFEUPNBUDIFEDPOUSPMT)PXFWFS UIFMBSHFJOUFSJOEJWJEVBMWBSJBUJPOEJTBMMPXFE BOVOFRVJWPDBMDPODMVTJPO5IFEJGGFSFOUJBMFYQSFTTJPOPGBOHJPHFOJDGBDUPSTBQQFBSFE NPSFQSPNJOFOUJO'(3UIBOJO1& 5IFPSJHJOPGCPUI1&BOE'(3QSPCBCMZTUBSUTJOUIF¹STUUSJNFTUFS CFGPSFUIFPOTFUPG PWFSUEJTFBTFEVSJOHUIFMBTUUSJNFTUFS0VS¹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

(10) "OHJPHFOJDHSPXUIGBDUPSTJOQSFFDMBNQTJBBOEGPFUBMHSPXUISFTUSJDUJPO. EJG¹DVMU)PXFWFS UIFUPGPMEJOEVDUJPOPGHFOFTJOUIFTFTNBMMHSPVQTQSPNJTFT TJHOJ¹DBOUEJGGFSFODFTXIFOHSPVQTDPVMECFFYQBOEFE $VSSFOULOPXMFEHFSFHBSEJOH1&TVHHFTUTUIBUEFGFDUJWFWBTDVMBSSFNPEFMMJOHPGNBUFS OBMTQJSBMBSUFSJFTMFBETUPJNQBJSFEJOWBTJPOPGUSPQIPCMBTUT QMBDFOUBMJOTVG¹DJFODZBOE JTDIFNJB<-VUUVO $BSNFMJFU>5IFBGGFDUFEQMBDFOUBSFMFBTFTTPMVCMFBOUJBOHJPHFOJD GBDUPST MJLFTPMVCMF'MU T'MU BOEFOEPHMJO T&OH <.BZOBSEFUBM $MBSLFUBM  C5KPBFUBM >5IFTFGBDUPSTBMUFSUIFBOHJPHFOJDCBMBODF NBJOMZCZOFVUSBMJT JOH7&('BOE1M(''VSUIFSNPSF UIFTFGBDUPSTBSFBCMFUPJOEVDFTZTUFNJDFOEPUIFMJBM EZTGVODUJPOBOE¹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¹STUUSJNFTUFSUJTTVFT *O UIF QSFTFOU TUVEZ  N3/" MFWFMT PG 1M('  "OH BOE 5*& BQQFBSFE VOSFHVMBUFE JO GVUVSF1&QBUJFOUTDPNQBSFEUPDPOUSPMT7&('" ,%3 'MUBOE"OHTIPXFEDPN QBSBCMF FYQSFTTJPO MFWFMT /P QSFWJPVT SFQPSUT XFSF GPVOE UP SFGFSFODF UIFTF EBUB JO ¹STUUSJNFTUFS UJTTVFT 0OMZ ¹STUUSJNFTUFS TFSVN EBUB BSF BWBJMBCMF  TIPXJOH SFEVDFE 1M('BOEJODSFBTFE7&('BOETºUJO¹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