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Introduction: High-density lipoproteins (HDLs) have several anti-atherosclerotic/anti-inflammatory properties and the apolipoprotein A-I (apoA-I), the main protein component of HDL, plays a major role. The aim of the present project was to investigate the impact of apoA-I on atherosclerosis development, phenotype and inflammation, through the use of genetically modified mice. Methods: This study was performed in C57Bl/6 wild-type mice, resistant to atherosclerosis development, and in three athero-prone mouse lines: apoEKO, apoEKO with the additional deletion of murine apoA-I (dKO) and dKO overexpressing human apoA-I (hA-I). These animals were fed a chow diet for 22 weeks. Cholesterolemia was quantified by FPLC analysis; atherosclerosis development was evaluated at the whole aorta by en-face analysis and at the aortic sinus and common coronary arteries by histology. Skin biopsies were processed for both light (LM) and transmission electron microscopy (TEM); moreover, lipids were extracted from skin and the lipid content were quantified. Finally, skin draining lymph nodes and spleens were harvested for histology and leukocyte populations were investigated by flow cytometry. Results: As expected, in wild-type mice all the cholesterol was found into the HDL fractions and in apoEKO mice the majority of cholesterol was present into the VLDL/LDL fractions. In dKO animals HDL-cholesterol was instead almost absent and VLDL/LDL-cholesterol was about 30% lower compared to apoEKO mice. hA-I mice were characterized by a large HDL-cholesterol peak and by a marked presence of VLDL/LDL particles although less prominent that in apoEKO mice. En-face analysis showed that dKO and apoEKO mice had a similar extent of atherosclerotic plaques at the aortic arch (6.9�5.6%, 7.2�5.5%, respectively). No atherosclerosis was instead observed in wild-type as well as in hA-I mice. At the aortic sinus, dKO mice showed a significant increase in lesion development compared to both apoEKO and hA-I mice (6.2�0.5x105?m2 vs. 3.2�0.7x105?m2 and 0.4�0.3x105?m2, p |
