Liver X receptors (LXRs) are implicated in the regulation of cholesterol homeostasis, inflammatory response and atherogenesis. Administration of LXR agonists inhibits the progress of atherosclerosis, and also increases plasma triglyceride levels, representing an obstacle to their use in treating this disease. The objective of this study was to develop an alternative approach that could overcome this obstacle. Eight-week-old low-density lipoprotein receptor-deficient (LDLR À/À ) mice were transplanted with hematopoietic stem cell (HSC)-enriched bone marrow cells transduced with lentivectors expressing either green fluorescent protein (GFP) (Lenti-SP-GFP, control) or LXRa (Lenti-SP-LXRa) driven by a synthetic macrophage promoter. At 4 weeks post-transplant, the mice were fed with a Western diet for 8 weeks and then killed. Compared with Lenti-SP-GFP mice, the Lenti-SP-LXRa mice had a 30% reduction in atherosclerotic lesions, which was accompanied by increases in levels of macrophage expression of cholesterol efflux genes apolipoprotein E and ATP-binding cassette A1, as well as decreases in plasma inflammatory cytokines interleukin-6 and tumor necrosis factor-a. Intriguingly, a 50% reduction of plasma triglyceride level was also observed. We conclude that HSC-based macrophage LXRa gene therapy ameliorates the development of atherosclerosis along with an unexpected concomitant reduction of plasma triglyceride levels in LDLR À/À mice. These findings highlight the potential value of macrophage LXR expression as an avenue for therapeutic intervention against atherosclerosis.

Case-finding algorithms accurately identify patients with Fabry disease in administrative databases. These algorithms can be used to collect population-based cohorts, find new FD cases and facilitate future research in epidemiology. Fabry disease should be added in the list of differential diagnoses for unclear pathologies and those taking an atypical disease course.

in in vitro and transplantation models, which represents a strategy for mitigating hnRNP K-mediated c-Myc activation in patients. Further studies, using fluorescence-anisotropy assays, identified small molecules that specifically disrupt these hnRNP K•MYC interactions. The efficacy of these compounds are now being characterized in vivo. Summary/Conclusion: These findings indicate that increased hnRNP K levels drive c-Myc expression in the absence of MYC translocations or amplifications and that this interaction may be therapeutically targeted.