Galectin-3 Gene Inactivation Reduces Atherosclerotic Lesions and Adventitial Inflammation in ApoE-Deficient Mice

Abstract

This study has examined the role of galectin-3 (GaL3), a multicompartmented N-acetyllactosamine-binding chimeric lectin, on atherogenesis in the ApoE-deficient mouse model of atherosclerosis. Pathological changes consisting of atheromatous plaques, atherosclerotic microaneurysms extending into periaortic vascular channels, and adventitial and periaortic inflammatory infiltrates were assessed in an equal number (n ‫؍‬ 36) of apolipoprotein (Apo)E-deficient mice and ApoE-GaL3 double-knockout mice. These mice were divided into three age groups, 21 to 23 weeks, 25 to 31 weeks, and 36 to 44 weeks of age. Results of this morphological analysis have shown an age-related increase in the incidence of aorta atheromatous plaques and periaortic vascular channels in ApoEdeficient mice. By contrast ApoE/GaL3 double-knockout mice did not show an increase in pathological changes with age. The 36-to 44-week group of ApoE

Accelerated Lipid-Induced Atherogenesis in Galectin-3-Deficient Mice

“…This is in keeping with our previous studies showing an acceleration of renal injury induced by diabetes, AGEs, and aging in Lgals3 Ϫ/Ϫ mice, [12][13][14] but it is in contrast with a recent report showing that C57BL/6J-ApoE null mice on standard diet develop attenuated atherosclerosis when crossbred with Lgals3 Ϫ/Ϫ mice. 27 However, in this report, Lgals3 Ϫ/Ϫ mice were on a 129 genetic background, known to be less prone to develop atherosclerotic lesions than the C57BL/6J background, 28 and the use of the F2 generation raises the possibility that some animals might have been homozygous for susceptibility genes. Moreover, difference in lesion number, but not size, was detected only at the oldest age examined, when the number of animals was small.…”

The role of galectin-3 and galectin-3–binding protein in venous thrombosis

“…11,12,[19][20][21][22][23][24][25] This study shows that gal3 and gal3bp are associated with murine thrombogenesis, that gal3 and gal3bp interact at the thrombus-vein wall interface, and that gal3 may be contributing to thrombosis through proinflammatory, IL-6-dependent mechanisms. Our findings suggest that gal3bp and gal3 may be potential therapeutic targets, and biomarkers, in human VT.…”

Molecular Biology of Atherosclerosis

“…Thus increased AGE-R1 expression was seen with a diet low in AGE which also was found to extend life in mice, while increased oxidant stress in diabetes or high AGE diet led eventually to downregulation of AGE-R1 (239,1661). AGE-R3 (also known as galectin-3) may serve as both an AGE clearance receptor and a mediator of macrophage endocytosis of modified LDL (1266). In fat-fed C57BL/6J mice, AGE-R3 deletion increased atherosclerosis and was associated with increased Th1 cell infiltration into lesions (813).…”