Human defensin alpha 1 (DEFA1) expression and interaction are associated with nucleotide oligomerization domain 2 (NOD2/CARD15)
GASTROENTEROLOGY
Authors: Yamamoto-Furusho, Jesus K.; Podolsky, Daniel K.
Abstract
Alpha defensins 1, 2, and 3 - Potential roles in dyslipidemia and vascular dysfunction in humans
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Authors: Lopez-Bermejo, Abel; Chico-Julia, Berta; Castro, Antoni; Recasens, Monica; Esteve, Eduardo; Biarnes, Josefina; Casamitjana, Roser; Ricart, Wifredo; Fernandez-Real, Jose-Manuel
Abstract
Objectives - alpha-Defensins are natural antibiotics made by neutrophils that have been reported to modulate cholesterol metabolism and vascular function; however, their role in vivo remains largely unknown. We hypothesized that alpha-defensins 1 to 3 (DEFA1-3) are associated with serum lipids and vascular reactivity in humans. Methods and Results - One hundred thirteen apparently-healthy White men, participants in a prospective study of cardiovascular risk factors, were assessed for a lipid profile, insulin sensitivity (SI, frequently-sampled intravenous glucose tolerance test), and non-stressed circulating DEFA1-3 (ELISA). In a subset of 52 subjects, vascular reactivity (high-resolution ultrasound of the brachial artery) was also assessed. Subjects in the highest quartile for plasma DEFA1-3 were found to be leaner and more insulin sensitive, and to have significantly reduced total and LDL-cholesterol, compared with subjects in the lowest quartile for circulating DEFA1-3 (P < 0.0001 to P < 0.002 for linear trend ANOVA). The associations with serum lipids persisted after adjustment for age, body mass index, insulin sensitivity, and smoking (which was associated with reduced plasma DEFA1-3 concentrations). Finally, endothelium-independent vasodilation increased with increasing circulating DEFA1-3 (P < 0.003) and this association was not explained by age, body mass index, serum cholesterol, insulin sensitivity, or smoking. Conclusions - Circulating DEFA1-3 are associated with serum cholesterol and vascular reactivity in humans. alpha-Defensins may have clinical implications in patients with either hypercholesterolemia or vascular dysfunction.