Ispitivanje povezanosti redoks statusa i telomera – telomeraza sistema kod bolesnika sa akutnim infarktom miokarda
Investigation of the relationship between redox status and telomere - telomerase system in patients with acute myocardial infarction
Author
Vukašinović, Aleksandra R.Mentor
Kotur-Stevuljević, JelenaCommittee members
Zdravković, MarijaBogavac-Stanojević, Nataša
Nešković, Aleksandar
Ostanek, Barbara
Metadata
Show full item recordAbstract
Kardiovaskularne bolesti ostaju vodeći uzrok smrtnost širom sveta i u Srbiji. U
patofiziološkoj osnovi ovih bolesti leži aterosklerotski proces. Razvoj i napredovanje
aterosklerotskog procesa usko su povezani sa oksidativnim stresom kao i narušenom funkcijom DNK
gledano kroz telomera-telomeraza sistem. U ovom istraživanju, pažnja je bila usmerena na bolesnike
sa akutnom infarkom miokarda sa elevacijom ST segmenta lečenih perkutanom koronarnom
intervencijom (pPCI), u okviru kojih su analizirani MINOCA bolesnici i bolesnici bez ugrađenog
stenta kao zasebne podgrupe. Parametri telomera-telomeraza sistema (dužina telomera leukocita i
aktivnost enzima telomeraze) kao i parametri redoks statusa (prooksidativni, antioksidativni i
oksidativni skor) analizirani su prvi put u populaciji u Srbiji, stoga je određen njihov referentni opseg.
U ovoj studiji urađena je i optimizacija i validacija metoda za određivanje telomera-telomeraza
sistema. Pokazano je da se kod bolesnika značajno skraćuje dužin...a telomera leukocita periferne krvi
skraćuje, pre pPCI, dok se nakon pPCI povećava, i šest meseci od akutnog infarkta miokarda ponovo
se vraća na nivo kao u trenutku pre pPCI. Sa druge strane, aktivnost enzima telomeraze se povećava
pre pPCI i ostaje povišena i 6 meseci nakon akutnog infarkta miokarda. U krvi ovih bolesnika izmeren
je i povećan oksidativni stres odnosno povišen prooksidativni i oksidativni skor pre pPCI, dok se
posle pPCI vrednost porooksidativnog skora smanjuje progresivno sve do 6 meseci nakon akutnog
infarkta miokarda. Sa druge strane, vrednosti oksidativnog skora posle pPCI se smanjuju i potom se
ponovo povećavaju nakon 6 meseci. Nasuprot njima, antioksidativni skor je snižen pre pPCI u odnosu
na bolesnike i ostaje nizak 6 meseci nakon akutnog infarkta miokarda. Poređenje grupa bolesnika je
pokazalo da je dužina telomera leukocita bila značajno duža kod kontrolne grupe u odnosu na
kardiovaskularne bolesnike, dok je aktivnost enzima telomeraze značajno viša kod svih podrupa
bolesnika u odnosu na kontrolnu grupu. Prooksidativni i oksidativni skor najviši su bili kod MINOCA
bolesnika i bolesnika bez stenta u odnosu na ostale grupe bolesnika i zdrave osobe, koji su imali slične
vrednosti. Nasuprot njima, antioksidativni skor je bio niži kod MINOCA bolesnika i bolesnika bez
stenta u odnosu na ostale grupe bolesnika i zdrave osobe. Slično kretanje parametara redoks stausa i
telomera-telomeraza sistema pokazano je u nekoliko tipova uzoraka ovih bolesnika analiziranih u
ovom istraživanju, kao što su arterijska krv pre pPCI i tromboaspirat dobijen tokom pPCI. S obzirom
na to da postoji konstantna potreba za specifičnijim markerima koji će u ranom stadijumu specifično
ukazati na akutni infarkt miokarda i eventulano biti korisni u praćenju ishoda bolesnika, novi
parametri redoks statusa i telomera-telomeraza sistema kombinovni su sa osnovnim biohemijskim
parametrima upotrebom statistističke analize glavnih komponenti, kako bi se dobili sveobuhvatniji
faktori sa dovoljnom tačnosti i specifičnosti da ispune pomenute zahteve...
Cardiovascular diseases remain the leading cause of death worldwide and in Serbia. Its
pathophysiological base is atherosclerosis. Development and progression of atherosclerotic process
is tightly connected to oxidative stress and DNA dysfunction, evaluated through the telomeretelomerase
system. In this study, the target group were patients with acute myocardial infarction,
candidates for primary percutaneous intervention (pPCI), which also included MINOCA and patients
without stent implementation. Since parameters of the telomere-telomerase system (leukocyte
telomere length and telomerase activity) as well as parameters of redox status (prooxidative,
antioxidative and oxidative score) were analyzed for the first time in the Serbian population, the
reference values were calculated. Additionally, in our study, telomere-telomerase system
measurement methods were optimised and in-house validation was performed in order to evaluate its
possible clinical use. It was shown that leukocyte tel...omere length is reduced in the acute state before
pPCI, while its increase was noticed after pPCI, and again decrease six months after the acute
myocardial infarction. On the other side, telomerase activity was increased before pPCI and stayed
elevated even six months after the acute myocardial infarction. Severe oxidative stress is measured
in the blood of these patients, more precise, increased values of prooxidative and oxidative scores are
noticed before pPCI, while after pPCI prooxidative score values were reduced and stayed low six
months after the acute myocardial infarction. Oxidative stress showed lower values after pPCI and
once again increased its values six months after the intervention. Oppositely, the antioxidative score
is reduces in samples before pPCI compared to healthy controls, while its values were dramatically
reduced after the pPCI and stayed low six months after the acute myocardial infarction. Analyzing
the groups of patients, leukocyte telomere length was significantly longer in healthy persons than in
all cardiovascular patients, while telomerase activity was significantly higher in all cardiovascular
patients compared to healthy persons. Prooxidative and oxidative score had the highest value in
MINOCA and patients without stent compared to other patients’ groups and healthy persons as well.
All opposite, antioxidative score had the lowest value in MINOCA and patients without stent
compared to other patients’ groups as well as healthy persons. Similar trend of parameters’ values
was noticed in redox status parameters and telomere-telomerase system parameters analyzed in
different sample types included in this research, like arterial blood sampled before pPCI and thrombus
obtained during pPCI. Since there is always a need for more specific biomarkers that will be able to
indicate the disease in an early stage or efficiently monitor disease outcome, new parameters of redox
status and the telomere-telomerase system were combined with basic biochemical parameters using
statistical principal component analysis in order to obtain new comprehensive factors, specific and
sensitive enough to fulfill expectations...