Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(-/-) mice.
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
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.
Ganguly Rituparna; Sahu Soumyadip; Ohanyan Vahagn; Haney Rebecca; Chavez Ronaldo J; Shah Shivani; Yalamanchili Siri; Raman Priya
Scientific reports
2017
2017-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1038/srep45279" target="_blank" rel="noreferrer noopener">10.1038/srep45279</a>
Trivalent chromium inhibits TSP-1 expression, proliferation, and O-GlcNAc signaling in vascular smooth muscle cells in response to high glucose in vitro.
Aorta/drug effects/metabolism; Cell Proliferation/*drug effects/genetics; Cells; Chromium/*pharmacology; Cultured; Fructosephosphates/metabolism; Genetic/drug effects/genetics; Glucose/*metabolism; Glutamine/genetics; Glycosylation/drug effects; Hexosamines/metabolism; Humans; Hyperglycemia/metabolism; Muscle; Myocytes; N-Acetylglucosaminyltransferases/genetics; O-glycosylation; Promoter Regions; reactive oxygen species; Reactive Oxygen Species/metabolism; Signal Transduction/*drug effects/genetics; Smooth; Smooth Muscle/*drug effects/metabolism; Thrombospondin 1/*antagonists & inhibitors/genetics; thrombospondin-1; Transcription; trivalent chromium; vascular smooth muscle cells; Vascular/*drug effects/metabolism
Trivalent chromium (Cr(3+)) is a mineral nutrient reported to have beneficial effects in glycemic and cardiovascular health. In vitro and in vivo studies suggest that Cr(3+) supplementation reduces the atherogenic potential and lowers the risk of vascular inflammation in diabetes. However, effects of Cr(3+) in vascular cells under conditions of hyperglycemia, characteristic of diabetes, remain unknown. In the present study we show that a therapeutically relevant concentration of Cr(3+) (100 nM) significantly downregulates a potent proatherogenic matricellular protein, thrombospondin-1 (TSP-1), in human aortic smooth muscle cells (HASMC) stimulated with high glucose in vitro. Promoter-reporter assays reveal that this downregulation of TSP-1 expression by Cr(3+) occurs at the level of transcription. The inhibitory effects of Cr(3+) on
Ganguly Rituparna; Sahu Soumyadip; Chavez Ronaldo J; Raman Priya
American journal of physiology. Cell physiology
2015
2015-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpcell.00256.2014" target="_blank" rel="noreferrer noopener">10.1152/ajpcell.00256.2014</a>