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Contractile protein expression is upregulated by reactive oxygen species in aorta of Goto-Kakizaki rat
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 306:H214-H224
- Publication Year :
- 2014
- Publisher :
- American Physiological Society, 2014.
-
Abstract
- Although it is known that blood vessels undergo remodeling in type 2 diabetes (T2D), the signaling pathways that underlie the structural and functional changes seen in diabetic arteries remain unclear. Our objective was to determine whether the remodeling in type 2 diabetic Goto-Kakizaki (GK) rats is evoked by elevated reactive oxygen species (ROS). Our results show that aortas from GK rats produced greater force ( P < 0.05) in response to stimulation with KCl and U46619 than aortas from Wistar rats. Associated with these changes, aortic expression of contractile proteins (measured as an index of remodeling) and the microRNA (miR-145), which act to upregulate transcription of contractile protein genes, was twofold higher ( P < 0.05) in GK than Wistar (age-matched control) rats, and there was a corresponding increase in ROS and decrease in nitric oxide signaling. Oral administration of the antioxidant Tempol (1 mmol/l) to Wistar and GK rats reduced ( P < 0.05) myocardin and calponin expression. Tempol (1 mmol/l) decreased expression of miR-145 in Wistar and GK rat aorta. To elucidate the mechanism through which ROS increases miR-145, we measured their levels in freshly isolated aorta and cultured aortic smooth muscle cells incubated for 12 h in the presence of H2O2 (300 μmol/l). H2O2 increased expression of miR-145, and there were corresponding nuclear increases in myocardin, a miR-145 target protein. Intriguingly, H2O2-induced expression of miR-145 was decreased by U0126 (10 μmol/l), a MEK1/2 inhibitor, and myocardin was decreased by anti-miR-145 (50 nmol/l) and U0126 (10 μmol/l). Our novel findings demonstrate that ROS evokes vascular wall remodeling and dysfunction by enhancing expression of contractile proteins in T2D.
- Subjects :
- Vascular smooth muscle
Transcription, Genetic
Physiology
Vascular Biology and Microcirculation
Myosins
Biology
Nitric Oxide
Muscle, Smooth, Vascular
Potassium Chloride
Nitric oxide
Cyclic N-Oxides
chemistry.chemical_compound
Downregulation and upregulation
Physiology (medical)
Calcium-binding protein
medicine.artery
Nitriles
Butadienes
medicine
Animals
Vasoconstrictor Agents
Rats, Wistar
Protein Kinase Inhibitors
Aorta
Cells, Cultured
chemistry.chemical_classification
Reactive oxygen species
Superoxide
Calcium-Binding Proteins
Microfilament Proteins
Nuclear Proteins
Rats
Up-Regulation
Cell biology
MicroRNAs
Diabetes Mellitus, Type 2
chemistry
Biochemistry
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
cardiovascular system
Trans-Activators
Spin Labels
Signal transduction
Reactive Oxygen Species
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 306
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....bfcef2bae63ef71713b3b564cf9f0705