IRGM1 regulates oxidized LDL uptake by macrophage via actin-dependent receptor internalization during atherosclerosis

Abstract

Macrophage derived foam cells are actively involved in the initial phase of atherosclerosis. Uptake of modified lipoprotein such as oxidized LDL (oxLDL) is a critical step for foam cell formation. CD36 is the major receptor mediating oxLDL uptake by macrophage. However, the molecular mechanism underlying CD36 mediated oxLDL uptake remains unclear. Here we reported that IRGM1 (IRGM in human), a member of immunity-related small GTPase family, is essential for the actin-dependent CD36 mediated oxLDL uptake by macrophage. IRGM/IRGM1 was highly expressed by macrophage around the atherosclerotic plaque and was up-regulated by oxLDL both in vitro and in vivo. Moreover loss of IRGM/IRMG1 significantly decreased oxLDL uptake in both mouse and human. Furthermore, the IRGM1 knock-out mice displayed impaired CD36 internalization in macrophage, which was associated with the deficiency of F-actin polymerization. These results revealed a novel function of IRGM1 in regulating oxLDL uptake by macrophage during atherosclerosis.

Quantification of strain and charge co-mediated magnetoelectric coupling on ultra-thin Permalloy/PMN-PT interface

“…Liu et al33 demonstrated a non-volatile switching of Verwey transition of Fe 3 O 4 with the 71° ferroelastic domain wall switching. The unique ferroelastic pathway was achieved by sweeping the electric field near the electric coercive field of PMN-PT.…”

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

“…The reduced citrate availability would probably have the effect of decreasing fatty acid synthesis as well as promoting glycolysis by reducing the inhibitory effect of citrate on phosphofructokinase (85). It is plausible that Irgm1 could play a direct role in lipid homeostasis, because it is a dynamin-like GTPase that associates with specific intracellular membrane compartments, including the Golgi, where it may alter membrane trafficking (11,12,21,25,52,78,87). Additionally, IRGM proteins have been reported to play roles in lipid droplet maintenance (27,78,88).…”

The IRGM rs10065172 variant increases the risk for steatosis but not for liver damage progression in Italian obese children

“…According to these observations, it has been demonstrated that there is an increased expression of IRGM by macrophages around the atherosclerotic plaque, suggesting a possible role of IRGM-mediated autophagy in cardiovascular disease. 9,10…”