The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypass

Abstract

Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24 h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers (p = 0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB.

The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes

“…Vascular endothelium from subjects with the CC genotype show NQO1 enzymatic activity by immunostaining, whereas subjects with the CT genotype show decreased activity and those with the TT genotype show no activity [8]. Furthermore, a recent report demonstrates an association between NQO1 polymorphism and the inflammatory response in cardiopulmonary bypass [18]. In that study, although there was a limited patient population, interleukin-6 secretion was higher and non-laminar flow was more deleterious in T allele carriers than in patients with the CC genotype during cardiopulmonary bypass.…”

NAD(P)H:Quinone Oxidoreductase 1 and its Potential Protective Role in Cardiovascular Diseases and Related Conditions

“…A recent epidemiological study involving 834 patients with type 2 diabetes demonstrated that patients with NQO1*2 polymorphism exhibited a higher prevalence of atherosclerotic plaques of carotid artery than those without this polymorphism [33]. Another study in patients undergoing standard coronary artery bypass grafting showed a greater inflammatory response, as revealed by increased serum interleukin-6 levels, in the subjects with NQO1*2 genotype as compared with the patients without this polymorphism [34]. Significantly higher levels of C-reactive protein, a biomarker for coronary heart disease, were reported to occur in coronary heart disease patients with lower NQO1 activity [35], indicating a protective role for NQO1 in cardiovascular inflammation.…”

Lipid Deposition Profiles Influence Foreign Body Responses

“…The second cluster contains genes that have been associated with the anti-inflammatory responses (Arg1, Spp1, Nqo1, Met, Il1rn, Slc7a2, Nt5e, Chst11, and Pdpn). [39][40][41][42][43][44][45][46][47] These gene were expressed at low levels on the unmodified PDMS surfaces. The opposite response was observed for the expression of these gene clusters on the Z2-Y12 modified surfaces.…”