| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Sun, Zhijun Wu, Xing Li, Weiping Peng, Hui Shen, Xuhua Ma, Lu Liu, Huirong Li, Hongwei |
| Abstract | Background Diabetes-induced vascular dysfunction may arise from reduced nitric oxide (NO) availability, following interaction with superoxide to form peroxynitrite. Peroxynitrite can induce formation of 3-nitrotyrosine-modified proteins. RhoA/ROCK signaling is also involved in diabetes-induced vascular dysfunction. The study aimed to investigate possible links between Rho/ROCK signaling, hyperglycemia, and peroxynitrite in small coronary arteries. Methods Rat small coronary arteries were exposed to normal (NG; 5.5 mM) or high (HG; 23 mM) D-glucose. Vascular ring constriction to 3 mM 4-aminopyridine and dilation to 1 μM forskolin were measured. Protein expression (immunohistochemistry and western blot), mRNA expression (real-time PCR), and protein activity (luminescence-based G-LISA and kinase activity spectroscopy assays) of RhoA, ROCK1, and ROCK2 were determined. Results Vascular ring constriction and dilation were smaller in the HG group than in the NG group (P < 0.05); inhibition of RhoA or ROCK partially reversed the effects of HG. Peroxynitrite impaired vascular ring constriction/dilation; this was partially reversed by inhibition of RhoA or ROCK. Protein and mRNA expressions of RhoA, ROCK1, and ROCK2 were higher under HG than NG (P < 0.05). This HG-induced upregulation was attenuated by inhibition of RhoA or ROCK (P < 0.05). HG increased RhoA, ROCK1, and ROCK2 activity (P < 0.05). Peroxynitrite also enhanced RhoA, ROCK1, and ROCK2 activity; these actions were partially inhibited by 100 μM urate (peroxynitrite scavenger). Exogenous peroxynitrite had no effect on the expression of the voltage-dependent K+ channels 1.2 and 1.5. Conclusions Peroxynitrite-induced coronary vascular dysfunction may be mediated, at least in part, through increased expressions and activities of RhoA, ROCK1, and ROCK2. |
| Related Links | https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-016-0372-6.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14712261 |
| DOI | 10.1186/s12872-016-0372-6 |
| Journal | BMC Cardiovascular Disorders |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2016-10-11 |
| Access Restriction | Open |
| Subject Keyword | Cardiology Cardiac Surgery Angiology Blood Transfusion Medicine Internal Medicine Medicine Public Health Peroxynitrite RhoA/ROCK Hyperglycemia Coronary artery Vasoconstriction Vasodilation Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
| Journal Impact Factor | 2/2023 |
| 5-Year Journal Impact Factor | 2.3/2023 |
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