Evaluation of Apoptosis with 99mTc-rhAnnexin V-128 and Inflammation with 18F-FDG in a Low-Dose Irradiation Model of Atherosclerosis in Apolipoprotein E-Deficient Mice.

Unlabelled: Low-dose radiation in apolipoprotein E-deficient (ApoE) mice has a protective effect with less subsequent atherosclerosis. Inflammation and apoptosis play major roles in the development of atherosclerosis. We evaluated the temporal pattern of the development of histologic atherosclerosis, inflammation with F-FDG, and apoptosis with Tc-rhAnnexin V-128 at 3 time points.

Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism.

Mycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy.

Insulin-degrading enzyme deficiency in bone marrow cells increases atherosclerosis in LDL receptor-deficient mice.

Background: Insulin-degrading enzyme (IDE), a protease implicated in several chronic diseases, associates with the cytoplasmic domain of the macrophage Type A scavenger receptor (SR-A). Our goal was to investigate the effect of IDE deficiency (Ide(-/-)) on diet-induced atherosclerosis in low density lipoprotein-deficient (Ldlr(-/-)) mice and on SR-A function.

Methods: Irradiated Ldlr(-/-) or Ide(-/-)Ldlr(-/-) mice were reconstituted with wild-type or Ide(-/-) bone marrow and, 6 weeks later, were placed on a high-fat diet for 8 weeks.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Regulation of lipid droplet cholesterol efflux from macrophage foam cells.

Cholesterol efflux from macrophages is the first and potentially most important step in reverse cholesterol transport, a process especially relevant to atherosclerosis and to the regression of atherosclerotic plaques. Increasingly, lipid droplet (LD) cholesteryl ester (CE) hydrolysis is being recognized as a rate-limiting step in cholesterol efflux. The traditional view on macrophage CE hydrolysis is that this pathway is entirely dependent on the action of neutral hydrolases, and numerous candidate CE hydrolases have been proposed to play a role in lipid hydrolysis in macrophages and atherogenesis.