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
ApoE-deficient 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(-/-)/GaL3(-/-) mice had a significantly lower number of atherosclerotic lesions (P < 0.004) and fewer
atheromatous plaques (P < 0.008) when compared with
ApoE(-/-)/GaL3+/+ mice of the same age.
ApoE(-/-)/GaL3(-/-) mice had a lower number of perivascular inflammatory infiltrates and mast cells than those found in
ApoE(-/-)/GaL3+/+ mice. The reduced number of perivascular mast cells may have resulted in a low level of
interleukin-4 that contributed to the reduction in the morphological parameters of
atherogenesis correlated with the lack of GaL3 expression. The effect of GaL3 deficiency on
atherogenesis decrease could be related to its function as a multifunctional
protein implicated in macrophage chemotaxis, angiogenesis,
lipid loading, and
inflammation.