Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Nox5 in human peripheral blood mononuclear cells: a potential prognostic biomarker in unstable diabetic coronary artery disease (#158)

Tomasz J Block 1 2 , Jairo A Pinzon-Cortes 2 , Karly C Sourris 2 , Jay C Jha 2 , Mark E Cooper 2 , James Shaw 3 , Karin Jandeleit-Dahm 2 4
  1. Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia
  2. Department of Diabetes, Monash University, Melbourne, VIC, Australia
  3. Department of Cardiology, Alfred Health, Melbourne, VIC, Australia
  4. German Diabetes Centre, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, North Rhine-Westphalia, Germany

Background: 
NADPH oxidase 5 (Nox5) plays a critical role in the pathogenesis of atherosclerosis via reactive oxygen species (ROS) production. It is expressed in peripheral blood mononuclear cells (PBMCs) and is increased in atherosclerotic plaques of diabetic patients with coronary artery disease (CAD), during acute coronary syndrome (ACS), and within diabetic kidney biopsies. Therefore, we assessed the suitability of Nox5 as a prognostic biomarker to identify patients at high risk for cardiovascular events, particularly those with comorbid diabetes and chronic kidney disease (CKD).

Methods:
200 patients aged 36-94 years underwent elective or emergency coronary angiography/angioplasty at the Alfred Hospital Catheter Laboratory. PBMCs from whole blood were processed for flow-cytometry to measure Nox5 protein and were correlated with patient clinical, biochemical, and angiographic characteristics.

Results:
Nox5 protein expression was increased in ACS with hemodynamically significant CAD versus stable CAD during elective angiography (15.28±1.7 vs 9.77±0.7 AU; p=0.0023), especially in diabetic patients with CKD presenting acutely versus electively (30.35±4.8 vs 11.99±2.0 AU; p=0.0002). Nox5 expression was higher in patients with stable angina who required intervention (PCI/CABG) versus medical management only (12.66±1.8 vs 8.03±0.9 AU; p=0.0014). At time of elective angiography, patients without CAD had lower Nox5 expression compared to those with stable CAD (4.03±1.0 vs 11.61±1.6 AU; p=0.014), with receiver operator characteristic (ROC) curve analysis demonstrating an area under the curve (AUC) of 0.75 (95% CI 0.62-0.88); p=0.0018 in discriminating those with or without CAD.

Conclusion:
Nox5 protein expression in PBMCs appears to be associated with the severity and instability of CAD, particularly in patients with diabetes and CKD. Increased Nox5 expression also seems to predict the presence of CAD and need for coronary intervention in patients with stable angina. Prognostic measurement of Nox5 may serve as a useful adjunctive biomarker to consider targeted interventions in those at high cardiovascular risk.