HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells

• DOI: 10.1073/pnas.1016086108
• Publication Date: 2011-04-12T10:00:50Z
• Authors: Jonathan E. Feig; James X. Rong; Raanan Shamir; Marie Sanson; Yuliya Vengrenyuk; Jianhua Liu; Katey Rayner; Kathryn Moore; Michael Garabedian; Edward A. Fisher
• Keywords: CD68; Monocyte; Apolipoprotein E; Scavenger Receptor

HDL cholesterol (HDL-C) plasma levels are inversely related to cardiovascular disease risk. Previous studies have shown in animals and humans that promotes regression of atherosclerosis. We hypothesized this was an ability promote the loss monocyte-derived cells (CD68(+), primarily macrophages macrophage foam cells) from plaques. To test hypothesis, we used established model atherosclerosis which plaque-bearing aortic arches apolipoprotein E-deficient (apoE(-/-)) mice (low HDL-C, high non-HDL-C) were transplanted into recipient with differing HDL-C non-HDL-C: C57BL6 (normal low non-HDL-C), apoAI(-/-) or apoE(-/-) transgenic for human apoAI (hAI/apoE(-/-); normal non-HDL-C). Remarkably, despite persistent elevated non-HDL-C hAI/apoE(-/-) recipients, plaque CD68(+) cell content decreased by >50% 1 wk after transplantation, whereas there little change hypolipidemia. The normalization associated their emigration induction chemokine receptor CCR7. Furthermore, laser-captured plaques, led expression inflammatory factors enrichment markers M2 (tissue repair) state. Again, none these beneficial changes observed suggesting a major requirement reverse transport effects HDL. Overall, results establish as regulator vivo migratory properties mouse atherosclerotic highlight phenotypic plasticity cells.