Atherosclerosis is a major risk factor for cardiovascular disease (CVD) and stroke. Galectin-3 is a carbohydrate-binding lectin implicated in the pathophysiology of CVD and is highly expressed within atherosclerotic lesions in mice and humans. The object of this present study was to use genetic deletion and pharmacological inhibition in a well-characterized mouse model of atherosclerosis to determine the role of galectin-3 in plaque development. Apolipoprotein-E/galectin-3 knockout mice were generated and fed a high-cholesterol "western" diet. Galectin-3 deletion had no consistent effect on the serum lipid profile but halved atherosclerotic lesion formation in the thoracic aorta (57% reduction), the aortic arch (50% reduction) and the brachiocephalic arteries. The aortic plaques were smaller, with reduced lipid core and less collagen. In apolipoprotein E-deficient (ApoE(-/-)) mice, there was a switch from high inducible nitric oxide expression in early lesions (6 weeks) to arginase-1 expression in later lesions (20 weeks), which was reversed in ApoE(-/-)/gal-3(-/-) mice. Administration of modified citrus pectin, an inhibitor of galectin-3, during the latter stage of the disease reduced plaque volume. We conclude that inhibiting galectin-3 causes decreased atherosclerosis. Strategies to inhibit galectin-3 function may reduce plaque progression and potentially represent a novel therapeutic strategy in the treatment of atherosclerotic disease.
Keywords: atherosclerosis; galectin-3; inflammation; macrophages; plaque.