title: Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE-/-mice.
abstract: 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.
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.|School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Ganguly
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.|School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA.
authors.forename: Soumyadip
authors.initials: S
authors.lastname: Sahu
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
authors.forename: Vahagn
authors.initials: V
authors.lastname: Ohanyan
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Haney
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
authors.forename: Ronaldo J
authors.initials: RJ
authors.lastname: Chavez
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
authors.forename: Siri
authors.initials: S
authors.lastname: Yalamanchili
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.|School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Raman
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D010848:Picolinic Acids / Q000494:pharmacology*; D013311:Streptozocin / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D010848:Picolinic Acids; D019700:Thrombospondin 1; D013311:Streptozocin; D005947:Glucose; C030614:picolinic acid