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  Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization

Tran Hien, T., Turczynska, K. M., Dahan, D., Ekman, M., Grossi, M., Sjogren, J., et al. (2016). Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(7), 3552-3568. doi:10.1074/jbc.M115.654384.

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 Creators:
Tran Hien, Thi, Author
Turczynska, Karolina M., Author
Dahan, Diana, Author
Ekman, Mari, Author
Grossi, Mario, Author
Sjogren, Johan, Author
Nilsson, Johan, Author
Braun, Thomas1, Author              
Boettger, Thomas1, Author              
Garcia-Vaz, Eliana, Author
Stenkula, Karin, Author
Sward, Karl, Author
Gomez, Maria F., Author
Albinsson, Sebastian, Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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Free keywords: STRETCH-DEPENDENT GROWTH; LIGHT-CHAIN PHOSPHATASE; GLYCATION END-PRODUCTS; RHO-KINASE; UP-REGULATION; DIABETIC-RATS; CA2+ CHANNELS; RESISTANCE ARTERIES; INDUCED ACTIVATION; DOWN-REGULATIONBiochemistry & Molecular Biology; cell differentiation; diabetes; glucose; microRNA (miRNA); Rho (Rho GTPase); vascular smooth muscle cells; actin polymerization;
 Abstract: Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells, but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hypercontractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, quantitative PCR, and Western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers were increased in isolated smooth muscle cells cultured under high compared with low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization, and myocardin-related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000370854500035
DOI: 10.1074/jbc.M115.654384
 Degree: -

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Title: JOURNAL OF BIOLOGICAL CHEMISTRY
Source Genre: Journal
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Publ. Info: 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Pages: - Volume / Issue: 291 (7) Sequence Number: - Start / End Page: 3552 - 3568 Identifier: ISSN: 0021-9258