Hyperlipidemias: Esteve E

Esteve E, Ricart W, Fernández-Real JM. · Sección de Diabetes, Endocrinología y Nutrición, Hospital Universitario de Girona "Dr Josep Trueta", Avenida de Francia s/n, 17007 Girona, Spain. · Clin Nutr. · Pubmed #15681098 No free full text.

Abstract: Inflammation leads to changes in lipid metabolism aimed at decreasing the toxicity of a variety of harmful agents and tissue repair by redistributing nutrients to cells involved in host defence. Acute phase response, mediated by cytokines, preserves the host from acute injury. When this inflammation becomes chronic, it might lead to chronic disorders as atherosclerosis and the metabolic syndrome. The activation of the inflammatory cascade will induce a decrease in HDL-cholesterol (HDL-C), with impairment in reverse cholesterol transport, and parallel changes in apolipoproteins, enzymes, anti-oxidant capacity and ATP binding cassette A1-dependent efflux. This decrease in HDL-C and phospholipids could stimulate compensatory changes, as synthesis and accumulation of phospholipid-rich VLDL which binds bacterial products and other toxic substances, resulting in hypertriglyceridemia. The final consequence is an increased accumulation of cholesterol in cells. When the compensatory response (inflammation) is not able to repair injury, it turns into a harmful reaction, and the lipid changes will become chronic, either by repeated or overwhelming stimulus, enhancing the formation of atherosclerotic lesions. Thus, the classical lipid changes associated with the metabolic syndrome (increased triglycerides and decreased HDL-C) may be envisioned as a highly conserved evolutionary response aimed at tissue repair. Under this assumption, the problem is not the response but the persistence of the stimulus.

López-Bermejo A, Chico-Julià B, Castro A, Recasens M, Esteve E, Biarnés J, Casamitjana R, Ricart W, Fernández-Real JM. · Unit of Diabetes, Endocrinology, and Nutrition, Dr Josep Trueta Hospital, Av. Francia s/n, 17007 Girona, Spain. · Arterioscler Thromb Vasc Biol. · Pubmed #17303777 links to  free full text

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 (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.