Nox5 in Human Peripheral Blood Mononuclear Cells: A Promising Biomarker for Unstable Diabetic Vascular Disease.

Human NADPH oxidase 5 (NOX5) is expressed and functionally active in peripheral blood mononuclear cells (PBMCs). Increased NOX5 expression has been demonstrated in atherosclerotic plaques of diabetic patients with associated coronary artery disease (CAD) and within diabetic kidney biopsies. We postulate that NOX5 expression in circulating PBMCs is particularly increased in diabetic patients with comorbid unstable CAD and chronic kidney disease (CKD). 64 males aged 33-85 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. In parallel, NOX5 gene expression was measured in PBMCs by qPCR. NOX5 protein expression in PBMCs was primarily driven by expression in monocytes (CD 45+/CD14+ cells) and was increased in diabetic patients with CKD versus without CKD (29.0±3.5 vs 12.8±2.3 AU; p=0.0007). CAD with acute presentation was associated with increased NOX5 expression versus elective presentation (24.7±2.7 vs 16.3±2.0 AU; p=0.013), especially in diabetic patients presenting acutely versus electively (28.2±3.5 vs 15.3±2.9 AU; p=0.0070). NOX5 expression was increased in diabetic patients with both CKD and acute presentation versus non-diabetic patients without CKD presenting electively (36.1±4.3 vs 11.9±3.4 AU; p=0.0003). A 3-fold upregulation of NOX5 gene was observed in diabetic patients with CAD and CKD versus diabetic patients with CAD but without CKD (p=0.044). Unstable CAD and CKD appear to be key factors for increased NOX5 expression in circulating PBMC in patients with clustering diabetic complications. Measurement of NOX5 in PBMCs may serve as a valuable prognostic biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]