Background: Slow coronary flow (SCF) is a coronary artery disorder characterized with delayed opacification of epicardial coronary arteries without obstructive coronary disease. The pathophysiological mechanisms of SCF remain unclear. One of the possible mechanisms that may participate in the pathology of SCF is endothelial dysfunction related to the inflammatory process. Interferon gamma (IFN-γ) is an inflammatory cytokine that acts through its specific receptor composed of two subunits, IFN-γR1 and IFN-γR2. Transcriptional activity of the gene encoding these subunits influences IFN-γ activity. This study aimed to investigate the gene expression of IFN-γ receptor subunits in peripheral blood mononuclear cells (PBMC) from patients with SCF.
Methods: The study was performed with 30 patients (22 male/8 female) aged 35-76 (52.8±11.7 years) with SCF and 15 sex- (11 male/4 female), Body Max Index (BMI)- and age-matched (54.73±9.42 years) healthy subjects. Total mRNA was extracted from PBMC and was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The relative expression values (2-ΔΔCt) between control and case groups were determined and the Mann-Whitney U test was used for statistical analysis.
Results: There was a significant increase in the gene expression of IFN-γR1 in PBMC from SCF patients vs. controls (P< 0.0001); but the differences in IFN-γR2 gene expression were statistically insignificant between patient and control groups (P= 0.853).
Conclusions: It can be concluded that IFN-γ gene expression may influence the function of microvasculature and thereby contribute to the pathophysiology of SCF.
Uvod: Spor koronarni protok (SKP) kao poremećaj koronarnih arterija odlikuje odložena opacifikacija epikardijalnih koronarnih arterija bez opstruktivne koronarne bolesti. Patofiziološki mehanizmi SKP još su nerazjašnjeni. Jedan od mehanizama koji potencijalno učestvuju u patologiji SKP je endotelna disfunkcija povezana sa inflamatornim procesom. Interferon gama (IFN-γ) je inflamatorni citokin koji deluje preko svog specifičnog receptora sastavljenog od dve podjedinice, IFN-γR1 i IFN-γR2. Transkripciona aktivnost gena koji kodira ove dve podjedinice utiče na aktivnost IFN-γ. Cilj ove studije bio je da se istraži genska ekspresija podjedinica receptora IFN-γ u mononuklearnim ćelijama periferne krvi (MĆPK) pacijenata sa SKP.
Metode: Studijom je obuhvaćeno 30 pacijenata (23 muškarca / 7 žena) starosti 35–76 (52,8±11,7) godina sa SKP i 15 (11 muškaraca / 4 žene) zdravih subjekata odgovarajućeg pola, indeksa telesne mase (ITM) i starosti (54,73 ±9,42 godina). Ukupna mRNK je ekstrahovana iz MĆPK i određena pomoću qRT-PCR. Određene su relativne vrednosti ekspresije između kontrolne i grupe pacijenata a Man-Vitnijev U test je upotrebljen za statističku analizu.
Rezultati: Postojao je značajan porast genske ekspresije IFN-γR1 u MĆPK pacijenata sa SKP u poređenju s kontrolama (P<0,0001), ali razlike između genske ekspresije IFN-γR2 pacijenata i kontrolnih subjekata nisu bile statistički značajne (P=0,853).
Zaključak: Može se zaključiti da genska ekspresija IFN-γR1 može uticati na funkciju mikrovaskulature i time doprineti patofiziologiji SKP.
Keywords: coronary artery disease; gene expression; inflammation; interferon gamma receptor; slow coronary flow.