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8-oxoguanine glycosylase (OGG1) is primarily involved in base excision repair (BER) by excising 8-oxoguanine, a mutagenic by-product of reactive oxygen species exposure. Increased markers of DNA damage/repair have been identified in atherosclerotic plaques, however their effects on plaque stability are poorly understood. We identified previously unreported differential OGG1 gene expression between patients with non ST-elevation myocardial infarction (NSTEMI) and controls as well as a correlation with plaque morphology, hence propose a potential target for plaque modulation.
39 patients with NSTEMI undergoing frequency domain optical coherence tomography-guided (FD-OCT) percutaneous coronary intervention (PCI) and 33 age/sex matched controls were recruited. A custom microarray was used to perform quantitative reverse transcription polymerase chain reaction (RT-qPCR) from purified isolated ribonucleic acid. Patients with diabetes, left ventricular impairment, bleeding diathesis, renal impairment, antiplatelet intolerance, malignancy, active inflammatory disease and prior coronary revascularization were excluded.
OGG1 was significantly up-regulated in NSTEMI versus control (p=0.001, figure B) and a negative correlation was found between RT-qPCR relative cycle threshold (Ct) and fibrous cap thickness (Spearman rho= -0.50, p=0.003, figure A). Corrected/relative Ct (to internal control gene) is inversely proportional to mRNA transcripts indicating higher OGG1 expression with a thicker fibrous cap.
OGG1 gene expression was up-regulated in NSTEMI compared with controls. Higher expression (lower Ct) correlated with a thicker fibrous cap, suggesting compensatory BER activity may increase in atherosclerotic cohorts in an attempt to confer atherosclerotic plaque stability.