Author + information
- Nikunj Shah1,
- Lisiane Meira1,
- Ruan Elliott1,
- Diana Bordin1,
- Clara Forrer-Charlier1,
- Mark Williams2 and
- Michael Mahmoudi3
DNA damage and repair activity is increasingly recognized in atherogenesis. By facilitating DNA strand joining by catalyzing phosphodiestere bond formation, DNA ligase is crucial in single/double stranded DNA break repair. We aimed to identify differential DNA ligase activity as well as a correlation between this and atherosclerotic plaque composition between non ST-elevation myocardial infarction (NSTEMI) and stable angina, providing a potential biomarker for plaque instability.
We recruited 35 patients presenting with NSTEMI and 34 stable angina patients undergoing percutaneous coronary intervention (PCI) guided by frequency domain optical coherence tomography (FD-OCT). Blood was drawn from the angiographic sheath during PCI and peripheral blood mononuclear cells (PBMC) were isolated using a density barrier strategy. Micro-plate DNA repair assays were performed on nuclear extracts prepared from isolated PBMCs. Subjects with diabetes, renal impairment, left ventricular impairment, bleeding diathesis, contraindication to antiplatelets, malignancy, active inflammatory disease and prior coronary revascularization were excluded.
DNA ligase activity was significantly higher in NSTEMI versus stable patients undergoing PCI (3094 units/gram protein vs 2041; p=0.03). Mean fibrous cap thickness was lower in the NSTEMI group (152.7μm vs 176.9; p=0.047). Also, fibrous cap thickness was negatively correlated with ligase activity in NSTEMI (Spearman’s correlation: rs= -0.6, p<0.001). Furthermore, lipid arc in the stable cohort was negatively correlated with the ligase assay (rs= -0.51, p=0.002).
Higher DNA repair, as measured by DNA ligase activity in NSTEMI compared with stable coronary disease, correlates with a thinner fibrous cap and subsequent atherosclerotic plaque instability.