Alpha defensins 1, 2, and 3: potential roles in dyslipidemia and vascular dysfunction in humans.
OBJECTIVE
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.


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 (S(I), 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.
López-Bermejo
Abel
A
Unit of Diabetes, Endocrinology, and Nutrition, Dr Josep Trueta Hospital, Av. Francia s/n, 17007 Girona, Spain. uden.alopez@htrueta.scs.es
Chico-Julià
Berta
B
Castro
Antoni
A
Recasens
Mònica
M
Esteve
Eduardo
E
Biarnés
Josefina
J
Casamitjana
Roser
R
Ricart
Wifredo
W
Fernández-Real
José-Manuel
JM
D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging; D002784:Cholesterol / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D014463:Ultrasonography; D014652:Vascular Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects*; D023084:alpha-Defensins / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D007328:Insulin; D023084:alpha-Defensins; D002784:Cholesterol