Tags

Type your tag names separated by a space and hit enter

Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization.
J Biol Chem. 2016 Feb 12; 291(7):3552-68.JB

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.

Authors+Show Affiliations

From the Departments of Experimental Medical Sciences and.From the Departments of Experimental Medical Sciences and.From the Departments of Experimental Medical Sciences and.From the Departments of Experimental Medical Sciences and.From the Departments of Experimental Medical Sciences and.Clinical Sciences, Lund University, BMC D12, SE-221 84 Lund, Sweden and.Clinical Sciences, Lund University, BMC D12, SE-221 84 Lund, Sweden and.the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, and.the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, and.the Department of Clinical Sciences in Malmö, Lund University, 205 02 Malmö, Sweden.From the Departments of Experimental Medical Sciences and.From the Departments of Experimental Medical Sciences and.the Department of Clinical Sciences in Malmö, Lund University, 205 02 Malmö, Sweden.From the Departments of Experimental Medical Sciences and sebastian.albinsson@med.lu.se.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26683376

Citation

Hien, Tran Thi, et al. "Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle Via Rho/Protein Kinase C and Actin Polymerization." The Journal of Biological Chemistry, vol. 291, no. 7, 2016, pp. 3552-68.
Hien TT, Turczyńska KM, Dahan D, et al. Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization. J Biol Chem. 2016;291(7):3552-68.
Hien, T. T., Turczyńska, K. M., Dahan, D., Ekman, M., Grossi, M., Sjögren, J., Nilsson, J., Braun, T., Boettger, T., Garcia-Vaz, E., Stenkula, K., Swärd, K., Gomez, M. F., & Albinsson, S. (2016). Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization. The Journal of Biological Chemistry, 291(7), 3552-68. https://doi.org/10.1074/jbc.M115.654384
Hien TT, et al. Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle Via Rho/Protein Kinase C and Actin Polymerization. J Biol Chem. 2016 Feb 12;291(7):3552-68. PubMed PMID: 26683376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization. AU - Hien,Tran Thi, AU - Turczyńska,Karolina M, AU - Dahan,Diana, AU - Ekman,Mari, AU - Grossi,Mario, AU - Sjögren,Johan, AU - Nilsson,Johan, AU - Braun,Thomas, AU - Boettger,Thomas, AU - Garcia-Vaz,Eliana, AU - Stenkula,Karin, AU - Swärd,Karl, AU - Gomez,Maria F, AU - Albinsson,Sebastian, Y1 - 2015/12/18/ PY - 2015/03/25/received PY - 2015/12/20/entrez PY - 2015/12/20/pubmed PY - 2016/7/7/medline KW - Rho (Rho GTPase) KW - actin polymerization KW - cell differentiation KW - diabetes KW - glucose KW - microRNA (miRNA) KW - vascular smooth muscle cells SP - 3552 EP - 68 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 291 IS - 7 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/26683376/Elevated_Glucose_Levels_Promote_Contractile_and_Cytoskeletal_Gene_Expression_in_Vascular_Smooth_Muscle_via_Rho/Protein_Kinase_C_and_Actin_Polymerization_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=26683376 DB - PRIME DP - Unbound Medicine ER -