Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation.Circulating high-density lipoprotein (HDL) particles, primarily small, dense, protein-rich HDL3, provide potent protection of LDL from oxidative damage by free radicals, resulting in the inhibition of the generation of pro-inflammatory oxidized lipids. HDL-mediated inactivation of lipid hydroperoxides involves their initial transfer from LDL to HDL and subsequent reduction to inactive hydroxides by redox-active Met residues of apolipoprotein A-I. Several HDL-associated enzymes are present at elevated concentrations in HDL3 relative to large, light HDL2 and can be involved in the inactivation of short-chain oxidized phospholipids. Therefore, HDL represents a multimolecular complex capable of acquiring and inactivating proatherogenic lipids.Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target.

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AIMTo evaluate novel risk factors and biomarkers of cardiovascular disease in celiac disease (CD) patients compared with healthy controls.METHODSTwenty adult patients with recent diagnosis of CD and 20 sex, age and body mass index-matched healthy controls were recruited during a period of 12 mo. Indicators of carbohydrate metabolism, hematological parameters and high sensitive C reactive protein were determined. Moreover, lipoprotein metabolism was also explored through evaluation of the lipid profile and the activity of cholesteryl ester transfer protein and lipoprotein associated phospholipase A2, which is also considered a specific marker of vascular inflammation. The protocol was approved by the Ethic Committee from School of Pharmacy and Biochemistry, University of Buenos Aires and from Buenos Aires Italian Hospital, Buenos Aires, Argentina.RESULTSRegarding the indicators of insulin resistance, CD patients showed higher plasma insulin levels [7.2 (5.0-11.3) mU/L vs 4.6 (2.6-6.7) mU/L, P < 0.05], increased Homeostasis Model Assessment-Insulin Resistance [1.45 (1.04-2.24) vs 1.00 (0.51-1.45), P < 0.05] and lower Quantitative Sensitive Check index [0.33 (0.28-0.40) vs 0.42 (0.34-0.65), P < 0.05] indexes. Folic acid concentration [5.4 (4.4-7.9) ng/mL vs 12.2 (8.0-14.2) ng/mL, P < 0.01] resulted to be lower and High-sensitivity C reactive protein levels higher (4.21 ± 6.47 mg/L vs 0.98 ± 1.13 mg/L, P < 0.01) in the patient group. With respect to the lipoprotein profile, CD patients showed lower high density lipoprotein-cholesterol (HDL-C) (45 ± 15 mg/dL vs 57 ± 17 mg/dL, P < 0.05) and apo A-I (130 ± 31 mg/dL vs 155 ± 29 mg/dL, P < 0.05) levels, as well as higher total cholesterol/HDL-C [4.19 (3.11-5.00) vs 3.52 (2.84-4.08), P < 0.05] and apo B/apo A-I (0.75 ± 0.25 vs 0.55 ± 0.16, P < 0.05) ratios in comparison with control subjects. No statistically significant differences were detected in lipoprotein-associated lipid transfer protein and enzymes.CONCLUSIONThe presence and interaction of the detected alterations in patients with CD, would constitute a risk factor for the development of atherosclerotic cardiovascular disease.