{"id":1305,"date":"2017-09-28T12:27:34","date_gmt":"2017-09-28T10:27:34","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/09\/28\/preeklampsia-v-suvislosti-s-exozomami-a-mikrorna\/"},"modified":"2017-09-28T12:39:35","modified_gmt":"2017-09-28T10:39:35","slug":"preeclampsia-in-connection-with-exosome-and-mirna","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/preeclampsia-in-connection-with-exosome-and-mirna\/","title":{"rendered":"Preeclampsia in connection with exosome and miRNA"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf \r\nattachment at the end of the paper.<\/span> <\/strong><\/pre>\n
\u00davod<\/strong><\/p>\n
Ka\u017ed\u00fd rok sa preeklampsia (PE) rozvinie u 10 mili\u00f3nov \u017eien na celom svete, pri\u010dom niektor\u00e9 z nich zomr\u00fa na PE a s \u0148ou s\u00favisiace hypertenzn\u00e9 ochorenia. Po\u010det det\u00ed, ktor\u00e9 zomr\u00fa na tieto komplik\u00e1cie, je tie\u017e ve\u013emi vysok\u00fd. PE pred\u00adstavuje jednu z najz\u00e1va\u017enej\u0161\u00edch komplik\u00e1ci\u00ed po\u010das tehoten\u00adstva, ktor\u00e1 postihuje 2 – 8 % v\u0161etk\u00fdch tehotn\u00fdch \u017eien a je zodpovedn\u00e1 takmer za 40 % pred\u010dasn\u00fdch p\u00f4rodov pred 35. t\u00fd\u017ed\u0148om tehotenstva(1)<\/sup>. PE je klinicky definovan\u00e1 ako nov\u00fd n\u00e1stup hypertenzie po\u010das druhej polovice tehotenstva. Pred\u00adpoklad\u00e1 sa, \u017ee PE sa za\u010d\u00edna asymptomatickou f\u00e1zou po\u010das prv\u00e9ho trimestra gravidity, ke\u010f u\u017e doch\u00e1dza k nedostato\u010dnej inv\u00e1zii trofoblastu a k ne\u00faplnej remodel\u00e1cii \u0161pir\u00e1lov\u00fdch art\u00e9ri\u00ed. Oba tieto procesy prispievaj\u00fa k zv\u00fd\u0161eniu oxida\u010dn\u00e9ho stre\u00adsu a vzniku syst\u00e9movej endotelovej dysfunkcie, ktor\u00e1 vedie k charakteristick\u00fdm prejavom PE v neskor\u0161\u00edch f\u00e1zach ochorenia(2)<\/sup>. V s\u00fa\u010dasnosti neexistuje \u00fa\u010dinn\u00e1 lie\u010dba, ktor\u00e1 by zabr\u00e1\u00adnila dlhodob\u00fdm n\u00e1sledkom PE, preto\u017ee samotn\u00e1 patofyziol\u00f3- gia ochorenia nie je \u00faplne objasnen\u00e1.<\/p>\n
 <\/p>\n
Exoz\u00f3my a tehotenstvo<\/strong><\/p>\n
Exoz\u00f3my s\u00fa mal\u00e9 bioakt\u00edvne vezikuly, tvoren\u00e9 r\u00f4znymi typ\u00admi buniek, z ktor\u00fdch s\u00fa sekretovan\u00e9 do okolit\u00fdch telov\u00fdch tekut\u00edn. Produkuj\u00fa ich najm\u00e4 T-bunky, B-bunky, dendritick\u00e9 bunky, kme\u0148ov\u00e9 bunky, neur\u00f3ny, epitelov\u00e9 bunky, krvn\u00e9 bun\u00adky, tumorov\u00e9 \u010di placent\u00e1rne bunky. Vyskytuj\u00fa sa najm\u00e4 v krv\u00adnej plazme, mo\u010di, plodovej vode, cerebrospin\u00e1lnej tekutine \u010di v materskom mlieku. Ve\u013ekos\u0165 exoz\u00f3mov sa pohybuje od 40 do 100 nm. Ich obsah je ve\u013emi variabiln\u00fd a \u0161irokospektr\u00e1lny. Obsahuj\u00fa d\u00f4le\u017eit\u00e9 prote\u00edny z mnoh\u00fdch prote\u00ednov\u00fdch rod\u00edn, ktor\u00e9 sa z\u00fa\u010dast\u0148uj\u00fa na viacer\u00fdch bunkov\u00fdch proce\u00adsoch. Pr\u00edtomn\u00e9 s\u00fa tie\u017e lipidy. D\u00f4le\u017eitou s\u00fa\u010das\u0165ou exoz\u00f3mov s\u00fa aj nukleov\u00e9 kyseliny, najm\u00e4 mikroRNA (miRNA) a mRNA(3) <\/sup>(obr\u00e1zok 1).<\/p>\n
Po\u010das tehotenstva sa matkin organizmus prisp\u00f4sobuje mnoh\u00fdm zmen\u00e1m a procesom. T\u00fato \u00falohu pln\u00ed najm\u00e4 pla\u00adcenta, ktor\u00e1 sa tie\u017e podie\u013ea na regul\u00e1cii rastu a v\u00fdvoja plo\u00addu. Ned\u00e1vne \u0161t\u00fadie potvrdili, \u017ee po\u010das tehotenstva placent\u00e1rne bunky, konkr\u00e9tne cytotrofoblasty a sync\u00fdciotrofoblasty\u00a0 u\u017e od 6. t\u00fd\u017ed\u0148a uvo\u013e\u0148uj\u00fa exoz\u00f3my, ktor\u00e9 sa n\u00e1sledne dost\u00e1\u00advaj\u00fa do matkinej cirkul\u00e1cie(4)<\/sup>. Placentou produkovan\u00e9 exoz\u00f3\u00admy maj\u00fa rovnak\u00fd tvar a ve\u013ekos\u0165 ako ostatn\u00e9 exoz\u00f3my, av\u0161ak obsahuj\u00fa \u0161pecifick\u00e9 prote\u00edny a miRNA, na z\u00e1klade ktor\u00fdch ich vieme odl\u00ed\u0161i\u0165. Exprimuj\u00fa typick\u00e9 markery CD63 a PLAP, tie\u017e proapoptotick\u00e9 molekuly FasL a TRAIL(5)<\/sup>. V porovnan\u00ed s in\u00fdmi exoz\u00f3mami maj\u00fa absenciu expresie MHC molek\u00fal, namiesto nich na svojom povrchu exprimuj\u00fa molekuly MICA\/B a RAET1\/ULBP1-5 podobn\u00e9 MHC. Je preuk\u00e1zan\u00e9, \u017ee koncentr\u00e1cia exoz\u00f3mov v perif\u00e9rnej krvi matky je vy\u0161\u00ad\u0161ia ako u netehotnej \u017eeny a mo\u017eno ich kvantifikova\u0165 pomo\u00adcou markera PLAP. Po\u010das fyziologick\u00e9ho tehotenstva sa t\u00e1\u00adto koncentr\u00e1cia v plazme matky zvy\u0161uje, ale v z\u00e1vislosti od \u0161t\u00e1dia tehotenstva sa m\u00f4\u017ee meni\u0165(6)<\/sup>. Placentou produkovan\u00e9 exoz\u00f3my m\u00f4\u017eu v obdob\u00ed tehotenstva ovplyv\u0148ova\u0165 aj imunit\u00adn\u00fd syst\u00e9m matky. V\u010faka svojim \u0161pecifick\u00fdm prote\u00ednom m\u00f4\u00ad\u017eu zn\u00ed\u017ei\u0165 prolifer\u00e1ciu a aktiv\u00e1ciu T-buniek, supresiu cytok\u00ednovej signaliz\u00e1cie, mo\u017en\u00fa indukciu apopt\u00f3zy, a tak prispieva\u0165 k celkovej ochrane plodu. Na druhej strane v\u0161ak nadmer\u00adn\u00e9 potla\u010denie imunitn\u00e9ho syst\u00e9mu matky m\u00f4\u017ee zv\u00fd\u0161i\u0165 rizi\u00adko infekci\u00ed v priebehu tehotenstva. Po\u010das tehotenstva nepro\u00addukuje exoz\u00f3my iba placenta, ale aj samotn\u00e9 embryo \u010di in\u00e9 matersk\u00e9 tkaniv\u00e1(5)<\/sup>.<\/p>\n
Celkov\u00fd po\u010det exoz\u00f3mov pr\u00edtomn\u00fdch v materskej plazme je pribli\u017ene 2-n\u00e1sobne vy\u0161\u0161\u00ed u \u017eien medzi 11. a\u017e 14. t\u00fd\u017ed\u0148om tehotenstva, u ktor\u00fdm bol medzi 22. – 28. t\u00fd\u017ed\u0148om diagnos\u00adtikovan\u00fd gesta\u010dn\u00fd diabetes mellitus, v porovnan\u00ed so \u017eenami s normoglykemick\u00fdm tehotenstvom. Tieto \u00fadaje nazna\u010duj\u00fa, \u017ee zmeny v koncentr\u00e1cii exoz\u00f3mov pr\u00edtomn\u00e9 v materskom krvnom obehu v po\u010diato\u010dn\u00fdch \u0161t\u00e1di\u00e1ch tehotenstva prispie\u00advaj\u00fa k rozvoju tehotensk\u00fdch komplik\u00e1cii (diabetes a PE) ne\u00adsk\u00f4r po\u010das tehotenstva(7)<\/sup>.<\/p>\n
Predch\u00e1dzaj\u00face in vitro \u0161t\u00fadie uk\u00e1zali, \u017ee hypoxia indu\u00adkuje uvo\u013e\u0148ovanie exoz\u00f3mov z trofoblastick\u00fdch buniek, kto\u00adr\u00e9 ovplyv\u0148uj\u00fa obsah aj interakciu s in\u00fdmi bunkami. PE je spojen\u00e1 s placent\u00e1rnou hypoxiou, ktor\u00e1 vedie k nedostato\u010d\u00adnej remodel\u00e1cii \u0161pir\u00e1lovej art\u00e9rie po\u010das prv\u00fdch 20 t\u00fd\u017ed\u0148ov tehotenstva\u00ae. Tieto pozorovania podporuj\u00fa domnel\u00fa u\u017eito\u010d\u00adnos\u0165 placent\u00e1rnych exoz\u00f3mov ako biomarker v ranom teho\u00adtenstve s rizikom vzniku PE u \u017eien. Av\u0161ak doteraz je m\u00e1lo in\u00adform\u00e1ci\u00ed o exoz\u00f3movom profile po\u010das PE tehotenstiev.<\/p>\n
 <\/p>\n
mikroRNA<\/strong><\/p>\n
V s\u00fa\u010dasnosti sa pozornos\u0165 s\u00fastre\u010fuje \u010doraz viac na mo\u00adlekuly miRNA. miRNA je mal\u00e1, pribli\u017ene 18 a\u017e 24 nukleotidov dlh\u00e1 nek\u00f3duj\u00faca sekvencia, ktorej najd\u00f4le\u017eitej\u0161ou vlastnos\u00ad\u0165ou je podie\u013eanie na regul\u00e1cii g\u00e9novej expresie. T\u00fa ovplyv\u0148uje na z\u00e1klade svojej komplementarity s mRNA na 3′ konci. \u013dud\u00adsk\u00fd gen\u00f3m k\u00f3duje viac ako 1 000 druhov miRNA a zd\u00e1 sa, \u017ee m\u00f4\u017eu ovplyv\u0148ova\u0165 a\u017e 60 % g\u00e9nov. V\u00e4\u010d\u0161ina miRNA mole\u00adk\u00fal je lokalizovan\u00fdch v bunk\u00e1ch, no niektor\u00e9 miRNA, zn\u00e1me aj ako cirkuluj\u00face, sa nach\u00e1dzaj\u00fa v extracelul\u00e1rnom priesto\u00adre, napr\u00edklad v telov\u00fdch tekutin\u00e1ch. Nezvy\u010dajn\u00e1 expresia miR\u00adNA je pozorovan\u00e1 pri r\u00f4znych patol\u00f3gi\u00e1ch a pri zmen\u00e1ch fy\u00adziologick\u00e9ho stavu(9)<\/sup>.<\/p>\n
Extracelul\u00e1rne miRNA (ECmiRNA) s\u00fa v s\u00fa\u010dasnosti pova\u00ad\u017eovan\u00e9 za vhodn\u00e9 biomarkery r\u00f4znych ochoren\u00ed, ke\u010f\u017ee ich expresn\u00fd profil z extracelul\u00e1rnych telov\u00fdch tekut\u00edn zobrazu\u00adje patofyziologick\u00fd stav organizmu. Na izol\u00e1ciu ECmiRNA je potrebn\u00e9 zvoli\u0165 vhodn\u00fa telov\u00fa tekutinu. Perif\u00e9rna krv sa neu\u00adkazuje ako vhodn\u00fd zdroj, preto\u017ee bunkov\u00e9 pozostatky z bie\u00adlych a \u010derven\u00fdch krviniek tie\u017e obsahuj\u00fa miRNA, ktor\u00e1 m\u00f4\u017ee ovplyvni\u0165 ECmiRNA anal\u00fdzu. V\u00fdhodnej\u0161ie sa preto zd\u00e1 pou\u00ad\u017eitie plazmy(10)<\/sup>.<\/p>\n
V\u010faka svojmu unik\u00e1tnemu zlo\u017eeniu s\u00fa exoz\u00f3my vhod\u00adn\u00e9 aj na r\u00f4zne diagnostick\u00e9 \u00fa\u010dely. Na diagnostiku mnoh\u00fdch ochoren\u00ed sa vyu\u017e\u00edvaj\u00fa najm\u00e4 ich prote\u00edny a miRNA. Zmena koncentr\u00e1cie exozom\u00e1lnych prote\u00ednov je asociovan\u00e1 s pato\u00adl\u00f3giami alebo aj s ich progresiou \u010di odpove\u010fou na oxida\u010d\u00adn\u00fd stres(4)<\/sup>.<\/p>\n
 <\/p>\n
miRNA a tehotenstvo<\/strong><\/p>\n
Expresia miRNA nie je zmenen\u00e1 len v priebehu ochore\u00adn\u00ed, ale aj po\u010das tehotenstva. Vtedy s\u00fa miRNA produkovan\u00e9 najm\u00e4 trofoblastick\u00fdmi bunkami placenty a predpoklad\u00e1 sa, \u017ee maj\u00fa vplyv na angiogen\u00e9zu, diferenci\u00e1ciu trofoblastu a re\u00adgul\u00e1ciu imunitn\u00e9ho syst\u00e9mu matky i plodu. V priebehu te\u00adhotenstva m\u00f4\u017eu by\u0165 takisto vyu\u017eit\u00e9 ako biomarkery, preto\u017ee pozmenen\u00e1 expresia miRNA m\u00f4\u017ee by\u0165 predzves\u0165ou kompli\u00adk\u00e1ci\u00ed. \u010ci u\u017e je tehotenstvo komplikovan\u00e9, alebo nie, placent\u00e1rne miRNA s\u00fa prim\u00e1rne lokalizovan\u00e9 v \u0161tyroch polycistronick\u00fdch klastroch. Klastre C19MC a miR-371-3 sa nach\u00e1dzaj\u00fa na chromoz\u00f3me 19, miR-17-92 na chromoz\u00f3me 13 a M14MC na chromoz\u00f3me 14. Po\u010das tretieho trimestra placenta okrem t\u00fdchto klastrov exprimuje let-7 rodinu, miR-34 rodinu, miR-29 klaster, miR-195 klaster a miR-181c. miRNA produkovan\u00e9 chromoz\u00f3mom 21, miR-99a, miR-125 b-2 a miR-155, m\u00f4\u017eu by\u0165 nadexprimovan\u00e9 u tehotn\u00fdch \u017eien v porovnan\u00ed s netehot- n\u00fdmi(11)<\/sup>.<\/p>\n
Najv\u00e4\u010d\u0161\u00ed zn\u00e1my \u013eudsk\u00fd miRNA klaster je C19MC a sklad\u00e1 sa z 54 miR g\u00e9nov. Okrem placenty je exprimovan\u00fd nedife\u00adrencovan\u00fdmi bunkami a uvo\u013e\u0148uje miRNA do matkinho obe\u00adhu pomocou exoz\u00f3mov tvoren\u00fdch placentou. Zvy\u0161n\u00e9 klastre obsahuj\u00fa podstatne menej g\u00e9nov(12)<\/sup>.<\/p>\n
Expresia miR g\u00e9nov neost\u00e1va po\u010das cel\u00e9ho tehotenstva rovnak\u00e1, miR z klastra C19MC sa zvy\u0161uj\u00fa od prv\u00e9ho trimestra a\u017e po tret\u00ed. G\u00e9ny z klastra C14MC s\u00fa upregulovan\u00e9 v prvom\u00a0trimestri a v tre\u0165om u\u017e klesaj\u00fa. Oproti prv\u00e9mu trimestru je v tre\u0165om trimestri tie\u017e upregulovan\u00fd let-7 a miR-34 rodiny a miR-29a, miR-195 a miR-181c. Tieto rodiny v\u00e4\u010d\u0161inou zo\u00adhr\u00e1vaj\u00fa \u00falohu v diferenci\u00e1cii, prolifer\u00e1cii \u010di apopt\u00f3ze buniek. Po\u010das gesta\u010dn\u00e9ho obdobia miRNA produkovan\u00e9 placentou zohr\u00e1vaj\u00fa d\u00f4le\u017eit\u00fa \u00falohu aj v imunitnom syst\u00e9me, na \u00farovni vrodenej aj z\u00edskanej imunitnej odpovede. Na rozdiel od in\u00fdch miRNA s\u00fa exprimovan\u00e9 po\u010das cel\u00e9ho tehotenstva(13)<\/sup>.<\/p>\n
 <\/p>\n
Preeklampsia v s\u00favislosti s exoz\u00f3mami a miRNA<\/strong><\/p>\n
Ako regula\u010dn\u00e9 molekuly m\u00f4\u017eu miRNA svojou dysregul\u00e1ciou v\u00fdznamne ovplyv\u0148ova\u0165 procesy sp\u00e1jan\u00e9 s v\u00fdvinom pla\u00adcenty a s cel\u00fdm tehotenstvom. Mnoho \u0161t\u00fadi\u00ed preuk\u00e1zalo, \u017ee zmenen\u00e1 \u00farove\u0148 expresie miRNA v placente je sp\u00e1jan\u00e1 s preeklampsiou(14)<\/sup>. Pozorovan\u00fdmi dysregul\u00e1ciami s\u00fa napr\u00edklad DNA metyl\u00e1cia a modifik\u00e1cia hist\u00f3nov, a teda pravdepodob\u00adne nie je n\u00e1hoda, \u017ee pr\u00e1ve miRNA m\u00e1 schopnos\u0165 regulova\u0165 g\u00e9ny t\u00fdmto sp\u00f4sobom. Naj\u010dastej\u0161\u00edmi zmenen\u00fdmi miRNA pri preeklampsii s\u00fa miR-210, miR-223 a miR-126, ktor\u00e9 \u00fazko s\u00fa\u00advisia s patogen\u00e9zou preeklampsie(15)<\/sup>.<\/p>\n
D\u00f4le\u017eit\u00fa \u00falohu zohr\u00e1va miRNA v procese angiogen\u00e9zy, ktor\u00e1 je rozhoduj\u00faca pri remodel\u00e1cii \u0161pir\u00e1lovit\u00fdch art\u00e9ri\u00ed. Pod\u013ea mnoh\u00fdch \u0161t\u00fadi\u00ed viacero upregulovan\u00fdch miRNA v preeklamptickej placente, napr. miR-210, miR-20 b, br\u00e1ni angiogen\u00e9ze a\/alebo prolifer\u00e1cii trofoblastu, inv\u00e1zii a migr\u00e1cii. Av\u0161ak niektor\u00e9 down-regulovan\u00e9 (miR-378a-5p, miR-376c), naopak, podporuj\u00fa prolifer\u00e1ciu trofoblastu aj inv\u00e1ziu(16)<\/sup>. Po\u00ad\u010das angiogen\u00e9zy s\u00fa nenahradite\u013en\u00e9 angiog\u00e9nne faktory, ktor\u00fdch bohat\u00fdm zdrojom je najm\u00e4 placenta, endometrium a deciduum. Proces angiogen\u00e9zy je iniciovan\u00fd rastov\u00fdmi fak\u00adtormi FGF, VEGF \u010di PlGF. G\u00e9ny t\u00fdchto faktorov s\u00fa v\u0161ak cie\u00ad\u013eom pre r\u00f4zne miRNA. Nasved\u010duje to tomu, \u017ee miRNA maj\u00fa kritick\u00fa \u00falohu pri tvorbe angiog\u00e9nnych faktorov po\u010das preklinick\u00e9ho \u0161t\u00e1dia preeklampsie. Zistilo sa, \u017ee miR-16, miR- 26 b, miR-29 b, miR-181a, miR-195, miR-222 a miR-335 s\u00fa nielen zv\u00fd\u0161en\u00e9 v preeklamptickej placente, ale ich cie\u013eom s\u00fa pr\u00e1ve VEGF-A a PlGF. Okrem toho niektor\u00e9 z nich ovplyv\u0148o\u00advali CYR61, ktor\u00fd je d\u00f4le\u017eit\u00fd pre vaskul\u00e1rnu integritu(17)<\/sup>. \u010eal\u00ad\u0161ia \u0161t\u00fadia poukazuje na miR-126, ktorej cie\u013eom je negat\u00edvny regul\u00e1tor faktora VEGF. T\u00e1to miRNA by preto mohla by\u0165 v bu\u00add\u00facnosti zvolen\u00e1 ako mo\u017en\u00fd terapeutick\u00fd cie\u013e. Okrem t\u00fdchto faktorov v\u0161ak miRNA pozit\u00edvne aj negat\u00edvne vpl\u00fdvaj\u00fa na \u010fal\u00ad\u0161ie faktory sp\u00e1jan\u00e9 s placent\u00e1rnou angiogen\u00e9zou. So vzni\u00adkom hypoxie zrejme s\u00favis\u00ed aj miR-210, ktorej zv\u00fd\u0161en\u00e1 \u00faro\u00adve\u0148 expresie je sp\u00e1jan\u00e1 s hypoxiou citliv\u00fdmi faktormi HIF-1a a NF-kB. Na z\u00e1klade bioinformatickej anal\u00fdzy sa predpokla\u00add\u00e1, \u017ee miRNA z rodiny miR-17, miR-20 a miR-20 b tie\u017e s\u00favi\u00adsia s angiogen\u00e9zou svoj\u00edm vplyvom na HIF-1a, interleuk\u00edn-8, EFNB2, EPHB4 a VEGF(18)<\/sup>. Bunky sync\u00fdciotrofoblastu produ\u00adkuj\u00fa \u0161pecifick\u00e9 placent\u00e1rne typy miRNA, ktor\u00e9 sa z buniek placenty vba\u013euj\u00fa do exoz\u00f3mov a n\u00e1sledne prech\u00e1dzaj\u00fa do te\u00adlov\u00fdch tekut\u00edn. Priamo z placenty sa teda miRNA m\u00f4\u017ee izo\u00adlova\u0165, ale jedine pri p\u00f4rode, preto\u017ee po\u010das tehotenstva je to bez ohrozenia plodu a matky nemo\u017en\u00e9. Preto sa izol\u00e1cia placent\u00e1rnych exoz\u00f3mov z matern\u00e1lnej plazmy jav\u00ed ako vhodn\u00fd neinvaz\u00edvny pr\u00edstup na z\u00edskanie placent\u00e1rnych miRNA s cie\u00ad\u013eom prenat\u00e1lnej diagnostiky(19)<\/sup>.<\/p>\n
 <\/p>\n
miRNA sekvenovanie<\/strong><\/p>\n
V\u010faka r\u00fdchlemu pokroku pri technol\u00f3gi\u00e1ch sekvenovania novej gener\u00e1cie vieme sekvenova\u0165 aj molekuly RNA s cie\u00ad\u013eom zisti\u0165 expresn\u00fd profil. Naj\u010dastej\u0161ie ide o mRNA a miRNA. V\u010faka vysokoparaleln\u00e9mu sekvenovaniu m\u00f4\u017ee byt\u2019 analyzo\u00advan\u00e1 cel\u00e1 \u013eudsk\u00e1 miRNA popul\u00e1cia, ktor\u00e1 m\u00f4\u017ee by\u0165 analy\u00adzovan\u00e1 aj pomocou qRT-PCR \u010di RNA mikro\u010dipu(20)<\/sup>. qRT-PCR a Microarray s\u00fa relat\u00edvne lacn\u00e9 a zau\u017e\u00edvan\u00e9 analytick\u00e9 me\u00adt\u00f3dy, no ich nev\u00fdhodou je, \u017ee vedia analyzova\u0165 jedine zn\u00e1me sekvencie. Pomocou sekven\u010dnej anal\u00fdzy mo\u017eno objavi\u0165 aj nov\u00e9, doposia\u013e neidentifikovan\u00e9 typy miRNA.<\/p>\n
 <\/p>\n
Z\u00e1ver<\/strong><\/p>\n
V\u00fdvoj technol\u00f3gie sekvenovania miRNA poskytol nov\u00e9 mo\u017enosti aj pre prenat\u00e1lnu diagnostiku. V s\u00fa\u010dasnosti sa vieme zamera\u0165 na \u0161pecifick\u00e9 placent\u00e1rne miRNA pri riziko\u00adv\u00fdch tehotenstv\u00e1ch. D\u00f4le\u017eit\u00e1 je napr\u00edklad diagnostika preeklampsie, ktor\u00e1 \u010dasto ohrozuje \u017eivot matky aj plodu. Zmena expresn\u00e9ho profilu t\u00fdchto molek\u00fal m\u00f4\u017ee nielen zabezpe\u00ad\u010di\u0165 v\u010dasn\u00fa diagnostiku, ale aj pom\u00f4c\u0165 objasni\u0165 pr\u00ed\u010diny tohto ochorenia \u010di n\u00e1jdenie vhodnej terapie.<\/p>\n
 <\/p>\n
LITERAT\u00daRA<\/p>\n
    \n
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  19. Sheikh AM, Small HY, Currie G, et al. Systematic Review of Micro-RNA Expression in Pre-Eclampsia Identifies a Number of Common Pathways Associated with the Disease. PLoS One 2016; 11: e0160808.<\/li>\n
  20. Wang J, Raimondo M, Guha S, et al. Circulating microRNAs in pancre\u00adatic juice as candidate biomarkers of pancreatic cancer. J Cancer 2005; 5: 696-705.<\/li>\n<\/ol>\n
     <\/p>\n
     <\/p>\n
     <\/p>\n
     <\/p>\n","protected":false},"excerpt":{"rendered":"
    *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper. \u00davod Ka\u017ed\u00fd rok sa preeklampsia (PE) rozvinie u 10 mili\u00f3nov \u017eien na celom svete, pri\u010dom niektor\u00e9 z nich zomr\u00fa na PE a s \u0148ou s\u00favisiace hypertenzn\u00e9 ochorenia. Po\u010det det\u00ed, ktor\u00e9<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[298],"tags":[570,567,179,571],"class_list":["post-1305","post","type-post","status-publish","format-standard","hentry","category-molecular-biology","tag-exosomes","tag-mirna","tag-next-generation-sequencing","tag-preeclampsia","typ_clanku-review-article"],"acf":{"abstrakt":"
    Preeclampsia (PE) is a multisystemic disorder related to high mortality and morbidity of a mother and her foe\u00adtus. One of the most serious aspects of preeclampsia is that there are no early warning signs or risk markers and pathogenesis of PE is still poorly explained. The discovery of microRNA has brought new insights into the basic knowledge of the regulation of gene expression, but it has also been found as an application of a new type of a biomarker in clinical practice. Exosomes may have a potential role as activating agents in endothelial dys\u00adfunction, a hallmark of PE. According to current knowledge, microRNA with different expression in PE cases ex\u00adists and may be important in the pathophysiology of the disease. MicroRNA markers of PE could help in under\u00adstanding the condition and pathogenesis and could be a tool for preventive strategies to reduce the prevalence, the severity of the disease and related complications.<\/p>\n
    Key words:<\/strong> exosomes, miRNA, next generation sequencing, preeclampsia<\/p>\n","casopis":[{"ID":1223,"post_author":"7","post_date":"2017-09-26 14:15:30","post_date_gmt":"2017-09-26 12:15:30","post_content":"
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    • Non-invasive markers of liver fibrosis<\/li>\r\n<\/ul>","post_title":"Newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2017-2","to_ping":"","pinged":"","post_modified":"2017-09-26 14:19:35","post_modified_gmt":"2017-09-26 12:19:35","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2017-2\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"110","upload_clanok":{"ID":1303,"id":1303,"title":"NEWSLAB 2-2017_Strie\u0161kov\u00e1","filename":"NEWSLAB-2-2017_Strie\u0161kov\u00e1.pdf","filesize":634720,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/09\/NEWSLAB-2-2017_Strie\u0161kov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/preeclampsia-in-connection-with-exosome-and-mirna\/newslab-2-2017_strieskova-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab-2-2017_strieskova-2","status":"inherit","uploaded_to":1305,"date":"2017-09-28 10:21:59","modified":"2017-09-28 10:21:59","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1305","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1305"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1305\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1305"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1305"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1305"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}