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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723896.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization
Authors:Thi Hien, T.; Turczynska, K. M.; Dahan, D.; Ekman, M.; Grossi, M.; Sjogren, J.; Nilsson, J.; Braun, T.; Boettger, T.; Garcia Vaz, E.; Stenkula, K.; Sward, K.; Gomez, M. F.; Albinsson, S.
Date of Publication (YYYY-MM-DD):2015-12-18
Title of Journal:J Biol Chem
Audience:Not Specified
Abstract / Description: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 hyper-contractility 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, qPCR and western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers was increased in isolated smooth muscle cells cultured under high compared to 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.
Free Keywords:Rho (Rho GTPase); actin polymerization; cell differentiation; diabetes; glucose; microRNA (miRNA); vascular smooth muscle cells
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Max Planck Institute for Heart and Lung Research, Germany. Lund University, Sweden; sebastian.albinsson@med.lu.se.
Identifiers:ISSN:1083-351X (Electronic) 0021-9258 (Linking) %R 10.1074/jbc.M115.654384
URL:http://www.ncbi.nlm.nih.gov/pubmed/26683376
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