a b s t r a c tSince heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations.

Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.

Objectives: This study examines the effects of sleep restricted to four hours for three consecutive nights on blood parameters, known to be associated with cardiovascular risk, in young healthy men. Material and methods: Eight young healthy men (age 24.5 ± 3.3 years) were studied in the sleep restricted group. Nine young healthy men (age 24 ± 2 years) were included in the control group and spent the days and nights in the sleep lab, while sleeping eight hours/night. One baseline night was followed by three nights of sleep restriction to four hours and by one recovery night of eight hours. Blood samplings were performed after the baseline night and after the third night of sleep restriction or without restriction for the control group. Results: A signifi cant increase in white blood cells (WBC) (5.79 ± 1.05 vs. 6.89 ± 1.31 10 3 cell/μl, p = 0.03), and neutrophils (3.17 ± 0.69 vs 4.24 ± 0.97 10 3 cell/μl, p = 0.01) was observed after the third night of sleep restriction. Other blood parameters were not affected. No signifi cant variation was observed in the control group. Conclusion: Sleep restriction affected WBC count, mainly neutrophils, considered as risk factor for cardiovascular disease. Stress induced by the short term sleep restriction could be involved in this observation.

No abstract

Over the past several years, considerable evidence has been obtained in support of the hypothesis that oxidants generated by the heme enzyme myeloperoxidase (MPO, EC1.11.2.2) play a key role in oxidation reaction of the artery wall. The enzyme, abundantly present in neutrophils and, to a lesser extent, in monocytes, is released during infl ammatory activation of immune cells. MPO produces hypochlorous acid (HOCl) by the reaction of hydrogen Abstract Oxidation of LDL by the myeloperoxidase (MPO)-H 2 O 2 -chloride system is a key event in the development of atherosclerosis. The present study aimed at investigating the interaction of MPO with native and modifi ed LDL and at revealing posttranslational modifi cations on apoB-100 (the unique apolipoprotein of LDL) in vitro and in vivo. Using amperometry, we demonstrate that MPO activity increases up to 90% when it is adsorbed at the surface of LDL. This phenomenon is apparently refl ected by local structural changes in MPO observed by circular dichroism. Using MS, we further analyzed in vitro modifi cations of apoB-100 by hypochlorous acid (HOCl) generated by the MPO-H 2 O 2 -chloride system or added as a reagent. A total of 97 peptides containing modifi ed residues could be identifi ed. Furthermore, differences were observed between LDL oxidized by reagent HOCl or HOCl generated by the MPO-H 2 O 2 -chloride system. Finally, LDL was isolated from patients with high cardiovascular risk to confi rm that our in vitro fi ndings are also relevant in vivo. We show that several HOCl-mediated modifi cations of apoB-100 identifi ed in vitro were also present on LDL isolated from patients who have increased levels of plasma MPO and MPO-modifi ed LDL. In conclusion, these data emphasize the specifi city of MPO to oxidize LDL. -Delporte,