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Inhibition of galectin-3 reduces atherosclerosis in apolipoprotein E-deficient mice.

TitleInhibition of galectin-3 reduces atherosclerosis in apolipoprotein E-deficient mice.
Publication TypeJournal Article
Year of Publication2013
AuthorsMackinnon AC, Liu X, Hadoke PWF, Miller MR, Newby DE, Sethi T
JournalGlycobiology
Volume23
Issue6
Pagination654-63
Date Published2013 Jun
ISSN1460-2423
KeywordsAnimals, Aorta, Thoracic, Apolipoproteins E, Arginase, Arginine, Atherosclerosis, Cell Line, Cell Movement, Fatty Acids, Nonesterified, Galectin 3, Humans, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Pectins, Plaque, Atherosclerotic, Triglycerides, Weight Gain
Abstract

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.

DOI10.1093/glycob/cwt006
Alternate JournalGlycobiology
PubMed ID23426722
PubMed Central IDPMC3641797
Grant List / / British Heart Foundation / United Kingdom
/ / Wellcome Trust / United Kingdom