Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.
(2016) In Journal of Biological Chemistry 291(7). p.68-3552- 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 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8504227
- author
- organization
-
- Minimal invasive cardiac surgery in valvular heart disease (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Molecular Vascular Physiology (research group)
- Vascular Physiology (research group)
- Cellular Biomechanics (research group)
- Thoracic Surgery
- Artificial Intelligence and Bioinformatics in Cardiothoracic Sciences (AIBCTS) (research group)
- Diabetic Complications (research group)
- Glucose Transport and Protein Trafficking (research group)
- Medical Protein Science (research group)
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 291
- issue
- 7
- pages
- 68 - 3552
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:26683376
- wos:000370854500035
- scopus:84964669870
- pmid:26683376
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M115.654384
- language
- English
- LU publication?
- yes
- id
- 75302ab4-6f55-4626-b676-92fbaa837a7c (old id 8504227)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26683376?dopt=Abstract
- date added to LUP
- 2016-04-04 07:19:12
- date last changed
- 2022-03-15 06:47:32
@article{75302ab4-6f55-4626-b676-92fbaa837a7c, 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 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 = {{Hien Tran, Thi and Turczynska, Karolina and Dahan, Diana and Ekman, Mari and Grossi, Mario and Sjögren, Johan and Nilsson, Johan and Braun, Thomas and Boettger, Thomas and Garcia Vaz, Eliana and Stenkula, Karin and Swärd, Karl and Gomez, Maria and Albinsson, Sebastian}}, issn = {{1083-351X}}, language = {{eng}}, number = {{7}}, pages = {{68--3552}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.}}, url = {{https://lup.lub.lu.se/search/files/7281294/5134701.pdf}}, doi = {{10.1074/jbc.M115.654384}}, volume = {{291}}, year = {{2016}}, }