Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.

Summary, in English

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.

• Author: Thi Hien Tran; Karolina Turczynska; Diana Dahan; Mari Ekman; Mario Grossi; Johan Sjögren; Johan Nilsson; Thomas Braun; Thomas Boettger; Eliana Garcia Vaz; Karin Stenkula; Karl Swärd; Maria Gomez; Sebastian Albinsson
• Department/s: Minimal invasive cardiac surgery in valvular heart disease; EXODIAB: Excellence of Diabetes Research in Sweden; Molecular Vascular Physiology; Vascular Physiology; Cellular Biomechanics; Thoracic Surgery; Artificial Intelligence and Bioinformatics in Cardiothoracic Sciences (AIBCTS); Diabetic Complications; Glucose Transport and Protein Trafficking; Medical Protein Science; Cardiovascular Research - Immunity and Atherosclerosis
• Publishing year: 2016
• Language: English
• Pages: 68-3552
• Publication/Series: Journal of Biological Chemistry
• Volume: 291
• Issue: 7
• Full text: - 1 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26683376?dopt=Abstract; http://dx.doi.org/10.1074/jbc.M115.654384
• Document type: Journal article
• Publisher: American Society for Biochemistry and Molecular Biology
• Topic: Cardiac and Cardiovascular Systems
• Status: Published
• Research group: Minimal invasive cardiac surgery in valvular heart disease; Molecular Vascular Physiology; Vascular Physiology; Cellular Biomechanics; Artificial Intelligence and Bioinformatics in Cardiothoracic Sciences (AIBCTS); Diabetic Complications; Glucose Transport and Protein Trafficking; Medical Protein Science; Cardiovascular Research - Immunity and Atherosclerosis
• ISBN/ISSN/Other: ISSN: 1083-351X