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

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 ben...

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Autores principales: Ganguly, Rituparna, Sahu, Soumyadip, Ohanyan, Vahagn, Haney, Rebecca, Chavez, Ronaldo J., Shah, Shivani, Yalamanchili, Siri, Raman, Priya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366888/
https://www.ncbi.nlm.nih.gov/pubmed/28345659
http://dx.doi.org/10.1038/srep45279
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author Ganguly, Rituparna
Sahu, Soumyadip
Ohanyan, Vahagn
Haney, Rebecca
Chavez, Ronaldo J.
Shah, Shivani
Yalamanchili, Siri
Raman, Priya
author_facet Ganguly, Rituparna
Sahu, Soumyadip
Ohanyan, Vahagn
Haney, Rebecca
Chavez, Ronaldo J.
Shah, Shivani
Yalamanchili, Siri
Raman, Priya
author_sort Ganguly, Rituparna
collection PubMed
description 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.
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spelling pubmed-53668882017-03-28 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 Sci Rep Article 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. Nature Publishing Group 2017-03-27 /pmc/articles/PMC5366888/ /pubmed/28345659 http://dx.doi.org/10.1038/srep45279 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ganguly, Rituparna
Sahu, Soumyadip
Ohanyan, Vahagn
Haney, Rebecca
Chavez, Ronaldo J.
Shah, Shivani
Yalamanchili, Siri
Raman, Priya
Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice
title Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice
title_full Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice
title_fullStr Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice
title_full_unstemmed Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice
title_short Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice
title_sort oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein tsp-1 expression in stz-induced type 1 diabetic apoe(−/−) mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366888/
https://www.ncbi.nlm.nih.gov/pubmed/28345659
http://dx.doi.org/10.1038/srep45279
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