Participation of macrophages in atherosclerotic lesion morphology in LDLr−/− mice

Abstract

Lyst beige (beige) mice crossed with LDL receptordeficient (LDLr ؊ / ؊ ) mice had a distinct atherosclerotic lesion morphology that was not observed in LDLr ؊ / ؊ mice. This morphology is often associated with a stable plaque phenotype. We hypothesized that macrophage expression of the beige mutation accounted for this distinct morphology. Cultured bone marrow-derived macrophages from LDLr ؊ / ؊ and beige,LDLr ؊ / ؊ mice were compared for their ability to accumulate cholesterol, efflux cholesterol, migrate in response to chemotactic stimuli through Matrigel ® -coated membranes, and express matrix metalloproteinase 9 (MMP9). No differences in cholesterol metabolism were identified. Beige,LDLr ؊ / ؊ macrophage invasion in vitro appeared to be less than LDLr ؊ / ؊ macrophage invasion but did not achieve significance. Nevertheless, tumor necrosis factor-␣ -induced MMP9 expression, secretion, and enzymatic activity of beige,LDLr ؊ / ؊ macrophages were all significantly decreased compared with those of LDLr ؊ / ؊ macrophages ( P Ͻ 0.05).

Atherosclerosis induced by endogenous and exogenous toll-like receptor (TLR)1 or TLR6 agonists

“…html). Results were reported as a percentage of the total aortic area that contained lesions ( 11 ).…”

Chronic internal exposure to low dose 137CS induces positive impact on the stability of atherosclerotic plaques by reducing inflammation in APOE-/- MICE

“…In parallel, collagen content and collagen gene expression were increased. Schiller et al [74] demonstrated macrophage rich and collagen poor lesions in the aortic roots of irradiated LDLR -/-mice after acute high dose (10 Gy) total body irradiation.…”

Expression of the Lystbeige mutation is atheroprotective in chow-fed apolipoprotein E-deficient mice

“…Atherosclerotic plaques in mice are regarded as resistant to rupture, and the relevance of mouse studies to model the final events precipitated by plaque disruption of human atherosclerotic lesions is controversial (21,22). Nevertheless, a previous report from our laboratory documented changes in plaque composition that define the double mutant BgLDLr 2/2 mouse, which resemble the characteristics of a more stable type of human lesion (10). Therefore, the present study was designed to identify features/mechanisms that control plaque stability in mice with the beige phenotype.…”

“…BM macrophages were cultured as described previously (10). After 5-7 days of culture, cells were harvested with Versene (Gibco), pooled for each mouse, counted, and seeded at ?2 3 10 6 cells per well onto six-well plates.…”

“…The atherosclerosis-accentuating effects of the beige mutation occur despite a reduction of the hyperlipidemia of the LDLr 2/2 mice and independently of the impaired cytolytic activity of beige NK cells and of both T-and B-lymphocyte-mediated acquired immune responses (9). Moreover, the impaired macrophage function by itself does not account for the distinct lesion morphology displayed by the double mutant BgLDLr 2/2 mice (10).…”