on February 15, 2007
Published online before print February 15, 2007, doi: 10.1161/ATVBAHA.106.138594
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Submitted on December 19, 2006
Accepted on February 1, 2007
Alpha Defensins 1, 2, and 3. Potential Roles in Dyslipidemia and Vascular Dysfunction in Humans
Abel López-Bermejo *;
From the Diabetes, Endocrinology, and Nutrition Unit (A.L.-B., B.C.-J., M.R., E.E., J.B., W.R., J.-M.F.-R.) and Internal Medicine (A.C.), Dr Josep Trueta Hospital, Girona; the Girona Institute for Biomedical Research (A.L.-B., B.C.-J., A.C., M.R., E.E., J.B., W.R., J.-M.F.-R.), Girona; and the Endocrine Laboratory (R.C.), University Clinical Hospital, Barcelona, Spain.
* To whom correspondence should be addressed. E-mail: uden.alopez{at}htrueta.scs.es.
Objectives--
-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 -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. -Defensins may have clinical implications in patients with either hypercholesterolemia or vascular dysfunction.
Key words: human neutrophil peptide • defensin • cholesterol • insulin resistance • vascular function.
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