20.500.12556/RUL-71275 Vpliv atrijske fibrilacije na gensko izražanje in sintezo nevrotrofinov v tkivih človeškega srca diplomska naloga Influence of atrial fibrillation on neutrotrophin gene expression and synthesis in human heart tissue Atrijska fibrilacija (AF) je najpogostejša kronična aritmija, za katero je značilno pospešeno, neredno in neusklajeno utripanje preddvorov. Pogosto jo sproţijo ektopična ţarišča, sčasoma pa privede do električnega in strukturnega preoblikovanja atrijev, kar še olajša ohranjanje motnje. Nevrotrofini so druţina nevrotrofičnih dejavnikov, ki uravnavajo preţivetje in diferenciacijo razvijajočih se ţivčnih celic ter vzdrţujejo njihove specifične povezave in funkcijo v odraslem organizmu. Vedno pomembnejša postaja njihova vloga v srčnoţilnem sistemu, kjer sodelujejo pri preţivetju srčnih mišičnih celic, angiogenezi in hipertrofiji. Učinki nevrotrofinov tako v srčnoţilnem sistemu kot v ţivčevju nakazujejo udeleţenost nevrotrofinskega sistema pri pojavu AF, zato smo ţeleli proučiti nivoje sinteze in genskega izraţanja nevrotrofinov in njihovih receptorjev v prisotnosti te motnje ritma. V ta namen smo pridobili vzorce seruma ter levega in desnega atrija 34 bolnikov z boleznimi zaklopk, od katerih je imelo 15 bolnikov reden srčni ritem, 19 bolnikov pa je imelo AF. Vsebnosti nevrotrofinov ţivčnega rastnega dejavnika (NGF), nevrotrofičnega dejavnika moţganskega izvora (BDNF) in nevrotrofina-3 (NT-3) smo določili z encimsko-imunskimi testi, izraţanje genov za NGF in NT-3 ter nevrotrofinskih receptorjev p75NTR, TrkA in TrkB pa z metodo veriţne reakcije s polimerazo v realnem času. Rezultati meritev so pokazali, da se serumske koncentracije nevrotrofinov v prisotnosti AF ne spremenijo. Bazalna vsebnost vseh treh proučevanih nevrotrofinov pri bolnikih z rednim ritmom je bila med levim in desnim atrijem primerljiva, izraţanje genov za NGF in p75NTR pa je bilo značilno manjše v levem atriju. Vsebnost NGF, BDNF in NT-3 pri bolnikih z motnjo ritma se ni značilno razlikovala od kontrolne skupine, prav tako nismo opazili pomembnih razlik v izraţanju genov za NGF in NT-3. V prisotnosti AF pa se je močno povišalo izraţanje gena za p75NTR v levem atriju ter zmanjšalo izraţanje gena za TrkA v desnem atriju. Značilnih sprememb v izraţanju gena za TrkB nismo zaznali. Zaključimo lahko, da atrijska fibrilacija ne vpliva na gensko izraţanje in sintezo nevrotrofinov, se pa v njeni prisotnosti spremeni izraţanje nevrotrofinskih receptorjev in s tem razmerje med njimi. To bi lahko pomembno spremenilo funkcijo ţivčevja in vplivalo na strukturno preoblikovanje tkiva atrijev človeškega srca. Atrial fibrillation (AF) is the most common sustained arrhythmia, characterized by rapid, irregular and uncoordinated activation of the atria. It is often triggered by ectopic foci and it eventually leads to atrial electric and structural remodelling, which only further facilitates its persistence. Neurotrophins are a family of neurotrophic factors, that regulate survival and differentiation of neurons during developement and maintain their specific connections and function in adulthood. Their role is becoming increasingly important in cardiovascular system, where they participate in cardiac myocyte survival, angiogenesis and hypertrophy.Since neurotrophin actions in both cardiovascular and nervous system point to the involvement of neurotrophic system in AF occurence, our aim was to determine the levels of synthesis and gene expression of neurotrophins and their receptors in the presence of this arrhythmia. For this purpose, we obtained serum and left and right atrial tissue samples from 34 patients with valvular disease. Among them, 19 suffered from AF and 15 of them had regular heart rhythm. We quantified nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels using enzyme-linked immunosorbent assay. Gene expression of neurotrophins NGF and NT-3 and neurotrophic receptors p75NTR, TrkA and TrkB was determined by real-time PCR. As shown by the results of these measurements, serum neurotrophin levels remained unchanged in the presence of AF. Basal protein levels of the three studied neurotrophins were comparable between left and right control atrium, yet NGF and p75NTR gene expression levels were significantly lower in left atrial tissue. When the arrhythmia group was compared to the control, no significant differences in atrial NGF, BDNF and NT-3 protein levels were observed. Also we found no changes in NGF and NT-3 gene expression. However, in the presence of AF p75NTR gene expression highly increased in the left atrium and TrkA gene expression in the right atrium decreased. No difference in TrkB gene expression was found. In conclusion, neurotrophin gene expression and synthesis are not influenced by atrial fibrillation. Nevertheless, the pattern of neurotrophin receptor gene expression is altered in its presence. This could notably alter the function of the nervous system and influence the structural remodelling of atrial tissue in human heart. atrijska fibrilacija nevrotrofini izražanje genov mehanizmi AF zdravljenje sinteza nevrotrofinov true false false [Ž. Kimovec] Slovenski jezik Angleški jezik Diplomsko delo 2015-07-10 22:04:23 2015-07-10 22:04:23 2022-08-01 14:12:12 0000-00-00 00:00:00 2011 0 Ljubljana 0 VI, 68 f. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-074 3180145 UNI_Kimovec_Ziva_2011.pdf UNI_Kimovec_Ziva_2011.pdf 1 B2FA157727A38948DF3596920F70F504 ac97e123d4fad537ab6543d9b14d922f0ac34e99b5079f2ecd92b4b86fc24030 3ebfdd70-a1ba-11eb-a523-00155dcfd717 20.500.12556/rul/cbc4dd66-2dda-469f-8fbd-85fbebb5784c https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=136048 Fakulteta za farmacijo 0 0 0