Title Biološki učinci molekule CD68 i enzima matrix metaloproteinaze 2 i 9 u aterosklerotskom procesu Title (english) Biological effects of CD68 molecule and matrix
metalloproteinase -2 and -9 enzymes in the atherosclerotic
process Author Andrica Lekić Mentor Ines Mrakovčić-Šutić (mentor)Mentor Zdenka Barićev Novaković (komentor)Committee member Gordana Đorđević (predsjednik povjerenstva)Committee member Edvard Galić (član povjerenstva)Committee member Hrvoje Jakovac (član povjerenstva)Granter University of Rijeka Defense date and country 2018, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine ThesaurusMESH - Medical Subject Headings )
Atherosclerosis
immunology
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
T-Lymphocytes, Regulatory
Abstract Cilj istraživanja: Ateroskleroza predstavlja upalnu, metaboličku, imunološku i
degenerativnu bolest, koja u svoj etiopatogenezi ujedinjuje genetske i okolišne čimbenike,
dovodeći do narušavanja radne sposobnosti i kvalitete života, a praćena je visokim stupnjem
morbiditeta i mortaliteta. Usprkos brojnim provedenim studijama, mnogo nedoumica je i dalje
prisutno. Nema idealnog biljega kojim bi se moglo pratiti napredovanje aterosklerotskog
procesa, a složena patofiziološka međudjelovanja koja obuhvaćaju promjene urođene i
stečene imunosti, izražaja molekule CD68 i enzima matrix metaloproteinaza nisu u ovakvom
obliku provedena. Cilj ovog istraživanja je bio ispitati postotak CD68 pozitivnih stanica i
stanica urođene imunosti u perifernoj krvi bolesnika s razvijenom aterosklerotskom bolešću i
u zdravih kontrola, te izražaj enzima MMP-2 i 9 u urinu, kao mogućih biljega za praćenje
promjena tijekom aterosklerotskog procesa.
Ispitanici i metode: Ispitanici su odabrani iz uzorka populacije ambulante obiteljske
medicine Doma zdravlja Primorsko-goranske županije. Bolesnici s aterosklerozom su imali
dijagnosticirane aterosklerotske promjene. Procjene imunološkog statusa vršili smo metodom
protočne citometrije iz stanica periferne krvi. Koncentracije enzima matrix metaloproteinaze-
2 i 9 smo određivali iz urina metodom enzimskog imunoeseja (ELISA). Dvosatnim testom
citotoksičnosti analizirali smo sposobnost ubijanja mononuklearnih stanica periferne krvi
protiv NK-osjetljive tumorske stanične linije. Statistički podaci su izračunati uz pomoć
kompjuterskog programa Statistica 13.0.
Rezultati: Bolesnici s razvijenom aterosklerozom su imali statistički značajno povišene
vrijednosti enzima MMP 2 i 9 u urinu. U perifernoj krvi su imali statistički značajno povišene
vrijednosti CD68+ molekule, NKT stanica i ukupnog perforina, te statistički značajno snižene
vrijednosti T regulacijskih stanica u usporedbi sa zdravim kontrolama. Povišene vrijednosti
NKT stanica ushodno koreliraju sa povišenom vrijednosšću enzima MMP-2 i 9, a nishodno sa
vrijednostima Tregs. Test citotoksičnosti je bio značajno snižen u odnosu na kontrolnu
skupinu.
Zaključak: Visoka koncentracija enzima MMP-2 i 9 praćena niskom koncentracijom T
regulacijskih stanica u bolesnika s aterosklerozom naglašava važnost regulacijske T imunosti
u etiopatogenezi ateroskleroze i mogućnosti T-regs posredovane imunoterapije.
Abstract (english) Objectives: Atherosclerosis is an inflammatory, metabolic, immune and degenerative disease
with genetic and environmental factors in its etiopathogenesis, leading to disruption of work
ability and quality of life, followed by a high degree of morbidity and mortality. Despite
numerous studies carried out on atherosclerosis, many questions remain to be solved. There is
no ideal marker for monitoring the progression of the atherosclerotic process. There are no
investigations about pathophysiological interactions between the cells of innate and acquired
immunity, the expression of CD68 molecule and the matrix metalloproteinase enzymes. The
aim of this study was to investigate the percentage of CD68 positive cells, innate immune
cells in peripheral blood of patients with atherosclerosis and healthy controls, as well as the
expression of MMP-2 and 9 in urine as possible markers for monitoring changes during the
atherosclerotic process.
Subjects and Methods: Patients were selected from a family doctor practice in Primorskogoranska
County. Atherosclerotic patients had diagnosed atherosclerotic changes.
Immunological status assays were performed by flow cytometry from peripheral blood cells.
The concentrations of enzymes matrix metalloproteinase-2 and 9 were determined by enzyme
immunoassays (ELISA) from urine. Two-hour cytotoxicity test was performed to investigate
the ability to kill of mononuclear cells from peripheral blood against the NK-sensitive tumor
cell line. Statistical data were calculated using the computer program Statistics 13.0.
Results: The patients with developed atherosclerosis had statistically significant increases in
MMP 2 and 9 enzyme urine levels. In the peripheral blood, they had statistically significant
increases in CD68 + molecule, NKT cells and total perforin + cells, and a statistically
significant decrease in T regulatory cells compared to healthy controls. The elevated values of
NKT cells correlated with elevated values of MMP 2 and 9 enzymes, and are down regulated
with the diminished Tregs values. The cytotoxicity test was significantly reduced in relation
to the control group.
Conclusion: High concentration of MMP 2 and 9 enzymes followed by significantly
diminished values of Tregs in atherosclerotic patients highlights the importance of regulatory
T cells in the etiopathogenesis of atherosclerosis and Treg-mediated immune therapy
Keywords
ateroskleroza
enzim matrix metaloproteinaza 2
enzim matrix metaloproteinaza 9
molekula CD68
regulacijske T stanice
Keywords (english)
atherosclerosis
enzyme matrix metalloproteinase 2
enzyme matrix metalloproteinase 9
molecule CD68
regulatory T cells
Language croatian URN:NBN urn:nbn:hr:184:997829 Study programme Title: Biomedicine Postgraduate (doctoral) study programme Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Created on 2019-01-17 15:36:49
