α-defensin:: Link between inflammation and atherosclerosis

Background: Several markers of inflammation predict the risk of thrombotic cardiovascular events in patients with atherosclerosis. However,,he mechanism by which vascular inflammation promotes atherothrombotic disease is incompletely understood. Human neulrophil peptides 1-3, also known as alpha-defensins, are found in human atherosclerotic arteries, inhibit LDL metabolism and fibrinolysis and promote Lp(a) binding. We asked, therefore, if alpha-defensins are risk factors for the presence and severity of atherosclerosis. Methods: alpha-Defensin was measured in skin biopsies taken from 53 male patients (age 58.7 +/- 11.3 years, mean +/- S.D.) immediately prior to coronary artery catheterization. Other established risk factors were measured concurrently. The correlation between alpha-defensin deposition in the skin and the severity of the coronary artery disease (CAD) was examined. Results: A statistically significant correlation was observed between the amount of alpha-defensin in skin and the severity of CAD (R = 0.40, p=0.003). Multiple regression analysis showed that skin alpha-defensin is an independent predictor for CAD severity (F=4.68, p=0.035). Logistic regression analysis confirmed that skin alpha-defensin independently predicted the likelihood for CAD (P=0.016, odds estimate 5.97, 95% CL 1.4-24.2). Conclusions: The deposition of alpha-defensin in the skin is a strong independent predictor of CAD in men. These results suggest a link between neutrophil activation and progression of atherosclerosis and provide a novel approach to assessment of risk factors for CAD. 0 2006 Elsevier Ireland Ltd. All rights reserved.