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Izražanje izbranih mikro RNA pri bolnikih z restenozo femoropoplitealne arterije po perkutani transluminalni angioplastiki
ID Vrščaj, Lucija Ana (Author), ID Božič Mijovski, Mojca (Mentor) More about this mentor... This link opens in a new window, ID Marc, Janja (Comentor)

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Abstract
Periferna arterijska bolezen (PAB) je zoženje arterij, najpogosteje v nogah. Običajno se pojavi pri napredovani oziroma generalizirani aterosklerozi, ki je vodilni vzrok smrti pri srčno-žilnih boleznih. Neposreden vzrok za nastanek PAB še ni znan, vodilna pa je teorija o poškodbi žilne stene, kateri sledi vnetni odgovor. Terapevtski pristop pri bolnikih s PAB običajno vključuje tudi endovaskularni poseg za razširitev arterije, to je perkutana transluminalna angioplastika (PTA). Uspešnost PTA ocenimo glede na pojav restenoze, torej ponovne zožitve arterij, kar se običajno pojavi v prvih šestih mesecih po posegu in prizadene kar tretjino bolnikov. Mehanizmi, ki sodelujejo pri PAB in restenozi, so še dokaj neraziskani, raziskave pa se sedaj usmerjajo tudi v mikro RNA (miRNA), ki sodelujejo pri endovaskularnih vnetnih procesih. miRNA so majhne nekodirajoče molekule, ki regulirajo izražanje genov po transkripciji. Zadnje raziskave so pokazale, da določene miRNA sodelujejo pri procesih ateroskleroze, predvsem pri diferenciaciji, rasti, proliferaciji in apoptozi vaskularnih celic. Namen naše naloge je bil ugotoviti, ali so tiste miRNA, ki sodelujejo pri procesih ateroskleroze in PAB, povezane tudi s procesom restenoze. Z obratno transkripcijo (RT) in kvantitativno verižno reakcijo s polimerazo v realnem času (qPCR) smo spremljali spremembe v izražanju treh miRNA: miRNA-590-5p, miRNA-1202 in miRNA-21 pri pacientih s PAB po angioplastiki femoropoplitealne arterije. V raziskavo smo vključili 123 bolnikov, in sicer 50 žensk in 73 moških, starih od 32 do 88 let. Bolnike smo glede na rezultate ultrazvočnega pregleda razdelili v dve skupini, z restenozo in brez nje. Rezultati so pokazali, da je restenozo v obdobju 12 mesecev po PTA doživelo 72 (59%) preiskovancev. Restenoza se je enako pojavljala pri obeh spolih in pri različni starosti, se je pa prej pojavila pri ženskah, in sicer je 6 mesecev po PTA restenozo doživelo 51% žensk in le 31% moških. Po 12 mesecih pa te razlike ni bilo več. Pri bolnikih, ki so doživeli restenozo, so bili nivoji izbranih miRNA po angioplastiki višji kot pri tistih, ki restenoze niso doživeli. Pri nobeni od preučevanih miRNA ni bilo signifikantne razlike med bolniki z restenozo in tistimi brez nje v času 1 mesec po PTA. Razlika se je pojavila 6 mesecev in 12 mesecev po PTA. Vse izbrane miRNA bi lahko bile potencialni napovedni kazalnik za restenozo, zato smo v model logistične regresije vključili spremembe v ekspresiji vseh miRNA po PTA. Najboljši napovedni kazalnik je sprememba v izražanju miRNA-1202, in sicer čim bolj se poveča njeno izražanje po PTA, tem večja je verjetnost za restenozo.

Language:Slovenian
Keywords:Periferna arterijska bolezen, ateroskleroza, perkutana transluminalna angioplastika, restenoza, miRNA
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2019
PID:20.500.12556/RUL-111001 This link opens in a new window
Publication date in RUL:21.09.2019
Views:1639
Downloads:330
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Secondary language

Language:English
Title:Expression of selected micro RNAs in patients with restenosis of femoropopliteal artery after percutaneous transluminal angioplasty
Abstract:
Peripheral artery disease (PAB) is a narrowing of the arteries, most often in the legs. The presence of PAB is an indicator of generalized atherosclerosis, which is the leading cause of death in patients with vascular disease. The direct cause of the disease is not yet known, but the leading theory is that of damage to the vascular wall followed by an inflammatory response. When artery stenosis is large enough, an endovascular intervention is performed to expand the artery, which is percutaneous transluminal angioplasty (PTA). The success of the PTA is mainly determined by the occurrence of restenosis, which is a renarrowing of arteries, as it affects about one third of patients in the first six months after the procedure. Mechanisms involved in PAB and restenosis are still quite unexplored and research is now directed at micro RNAs (miRNAs), which are involved in endovascular inflammatory processes. miRNA are small non-coding molecules that regulate the expression of genes after transcription. Recent studies have shown that certain miRNAs are involved in atherosclerotic processes, namely in differentiation, growth, proliferation, and apoptosis of vascular cells. The purpose of our research was to determine whether those miRNAs involved in the processes of atherosclerosis and PAB are also related to the process of restenosis. Changes in the expression of three miRNAs: miRNA-590-5p, miRNA-1202 and miRNA-21 were monitored with reverse transcription (RT) and real-time polymerase chain reaction (qPCR) in patients with PAB following PTA of the femoropopliteal artery. The study included 123 patients of which 50 were women and 73 were men, aged 32-88. Based on the results of the ultrasound examination, patients were divided into two groups, with and without restenosis. 72 (59%) subjects experienced restenosis in the first 12 months after PTA. The occurrence of restenosis was the same with regard to sex and age but it had developed earlier in women, where 6 months after PTA 51% of women suffered from restenosis in comparison to just 31% of men. This difference was absent after 12 months. The expression of the selected miRNAs in blood after angioplasty increased more in patients who experienced restenosis than those without restenosis. There was no significant difference in the expression of all three miRNAs between patients with restenosis and those without it 1 month after PTA but there was a difference between the restenosis and non-restenosis group at 6 months and 12 months after PTA. All of the selected miRNAs could be a potential predictive indicator for restenosis and therefore changes in the expression of all miRNA after PTA were included in the logistic regression model. The best predictive indicator is the change in the expression of miRNA-1202, the more its expression after PTA is increased the greater the likelihood of restenosis.

Keywords:Peripheral artery disease, atherosclerosis, percutaneous transluminal angioplasty, restenosis, miRNA

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