Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(-/-) mice.

Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(-/-) mice.

Ganguly Rituparna; Sahu Soumyadip; Ohanyan Vahagn; Haney Rebecca; Chavez Ronaldo J; Shah Shivani; Yalamanchili Siri; Raman Priya

Scientific reports

2017

2017-03

Increasing evidence suggests thrombospondin-1 (TSP-1), a potent proatherogenic matricellular protein, as a putative link between hyperglycemia and atherosclerotic complications in diabetes. We previously reported that the micronutrient chromium picolinate (CrP), with long-standing cardiovascular benefits, inhibits TSP-1 expression in glucose-stimulated human aortic smooth muscle cells in vitro. Here, we investigated the atheroprotective action of orally administered CrP in type 1 diabetic apolipoprotein E-deficient (ApoE(-/-)) mice and elucidated the role of TSP-1 in this process. CrP decreased lipid burden and neointimal thickness in aortic root lesions of hyperglycemic ApoE(-/-) mice; also, smooth muscle cell (SMC), macrophage and leukocyte abundance was prevented coupled with reduced cell proliferation. Attenuated lesion progression was accompanied with inhibition of hyperglycemia-induced TSP-1 expression and reduced protein O-glycosylation following CrP treatment; also, PCNA and vimentin (SMC synthetic marker) expression were reduced while SM-MHC (SMC contractile marker) levels were increased. To confirm a direct role of TSP-1 in diabetic atherosclerosis, hyperglycemic TSP-1(-/-)/ApoE(-/-) double knockout mice were compared with age-matched hyperglycemic ApoE(-/-) littermates. Lack of TSP-1 prevented lesion formation in hyperglycemic ApoE(-/-) mice, mimicking the atheroprotective phenotype of CrP-treated mice. These results suggest that therapeutic TSP-1 inhibition may have important atheroprotective potential in diabetic vascular disease.

Animals; Aorta/drug effects/metabolism; Apolipoproteins E/*metabolism; Atherosclerosis/*drug therapy/metabolism; Diabetes Mellitus; Diabetic Angiopathies/drug therapy/metabolism; Experimental/chemically induced/drug therapy/metabolism; Glucose/metabolism; Glycosylation/drug effects; Hyperglycemia/*drug therapy/metabolism; Inbred C57BL; Knockout; Male; Mice; Myocytes; Picolinic Acids/*pharmacology; Smooth Muscle/drug effects; Streptozocin/*pharmacology; Thrombospondin 1/*metabolism; Type 1/chemically induced/*drug therapy/metabolism

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