Investigation of nuclear factor erythroid 2 related factor 2 (NFR2) and thyol / disulphate level in coronary artery disease in-stent restenosis

OBJECTIVE: In the last 30 years, percutaneous coronary interventions (PCI), especially stent implantation, has been the standard treatment in coronary artery disease, but the high rate of in-stent restenosis (ISR) limits the benefit of PCI. The most common cause of restenosis is the result of a healing response to arterial damage during PCI. The underlying mechanism is the involvement of an excessive inflammatory and proliferative response to oxidative stress, thus the development of neointimal hyperplasia. In any case of oxidative stress, antioxidant thiol / disulfate hemostasis plays a role against free oxygen radicals. Serum Nuclear Factor Erythroid 2 Related Factor2 (NRF2) provides the resistance and repair of tissue against damage with its antioxidant and detoxification properties during oxidative stress. It was aimed to measure NRF2 and thiol / disulphate levels, considering that the connection between oxidative stress and thiol / disulphate and NRF2 may allow early diagnosis and treatment of stent restenosis. MATERIAL AND METHOD:76 patients were included in the study. Coronary angiography (CAG) images of 76 stable angina patients admitted to our hospital between March and December 2020 were evaluated. 25 patients with ISR of 51 patients with a history of everolimus-releasing Promus stent in the coronary artery (at least 3 months past) were divided into group 1 and group 2 with 26 patients without ISR. Group 3; 25 patients were recruited from patients with normal CAG who had no previous coronary artery disease. In all three groups, NRF2, Total Thiol, Native Thiol, Disulfide, Total Thiol / Disulfide ratio, Native Thiol / Disulfide ratio and Native Thiol / Total Thiol ratio were measured. RESULTS: NRF2 was significant (p = 0.029); it was found in group 1 (105.97 pg / mL), group 2 (131.53 pg / mL) and group 3 (116.54 pg / mL). In terms of NRF2, only group1 and group2 were significant compared to each other. (p=0.01). Total thiol: it was higher and significant in group 3 (738.76 micromole / L) compared to group 1 (626.11 micromole / L) and group 2 (630.27 micromole / L). (p = 0.014). Group 3 in terms of total thiol; It was found to be significantly higher than group1 and group 2 (p = 0.009, p = 0.013). No difference was found between group 1 and group 2 in terms of total thiol (p = 0.922). Natif tiyol; it was high and significant in the group 3 (570.53 micromol/L) compared to group1 (483.91 micromoles/L) and group 2 (501 micromoles/L). (p:0,006) Group 3 in natif tiyol was found to be significantly higher than group1 and group 2 (p=0.003, p=0.015). There was no difference between group 1 and group 2 in terms of natif tiyol (p=0.54). In addition, the means of Disulfide and Tiyol/Disulfide do not differ statistically significantly according to groups (p>0.05). CONCLUSION: In our study, when patients with coronary artery disease were compared, NRF2 values were found to be significantly higher in the group that did not develop ISR. Total thiol and native thiol values were lower in patients with coronary artery disease than those without coronary artery disease. Thiol / disulfate balance can be used as an oxidative stress marker in the early diagnosis of coranary artery disease, and NRF2 can provide early diagnosis and treatment of stent restenosis. KEYWORDS: NRF2, Tiyol/ Dysulfat, Neointimal Hyperplasia, In-Stent Restenosis