Related Experiment Video
Updated: Oct 13, 2025
Isolation of Mouse Coronary Endothelial Cells
Published on: July 3, 2016
Endothelial dysfunction caused by circulating microparticles from diabetic mice is reduced by PD98059 through ERK and
Kumiko Taguchi1, Nozomu Kaneko1, Kanami Okudaira1
1Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, 142-8501, Japan.
Abstract:
Endothelial dysfunction contributes to the development of diabetic complications and the production of circulating microparticles (MPs). Our previous study showed that diabetic mice-derived MPs (DM MPs) had increased levels of extracellular regulated protein kinase 1/2 (ERK1/2) and impaired endothelial-dependent relaxation in aortas when compared with control mice-derived MPs. This study was designed to investigate whether PD98059, an ERK1/2 inhibitor, affects the function of aortas and DM MPs. MPs were obtained from streptozotocin-induced DM, DM after PD98059 treatment, and ICR mice as control. The mice and MPs were then analyzed on the basis of their vascular function and enzyme expressions. Compared with the controls, platelet-derived MPs and ERK1/2 levels in the MPs were significantly elevated in the DM but showed little change in PD98059-treated DM. PD98059 mainly decreased ERK1/2 phosphorylation in the MPs. In the aortas of DM and DM MPs the endothelium-dependent vascular function was impaired, and there was a significantly greater improvement in the vascular function in the PD98059-treated DM aortas and the aortas treated with PD98059-treated DM MPs than in DM aortas and the aortas treated with DM MPs. Furthermore, DM MPs increased ERK1/2 and intracellular adhesion molecule-1 (ICAM-1) expressions in the aortas, but PD98059-treated DM MPs did not show these effects. For the first time, these results indicate that PD98059 treatment improves endothelial dysfunction in DM, and adhesion properties of DM MPs can be partly blocked by PD98059 via ERK and ICAM-1. These effects may explain some of the vascular complications in diabetes.
Insights
Diabetic mice microparticles (MPs) impair blood vessel function via elevated ERK1/2. Treating diabetic mice with PD98059, an ERK1/2 inhibitor, improved vascular function and reduced MP adhesion, suggesting a therapeutic target for diabetic complications.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Medicine
Background:
- Endothelial dysfunction is a key factor in diabetic complications.
- Circulating microparticles (MPs) are elevated in diabetes and linked to vascular impairment.
- Diabetic mice-derived MPs (DM MPs) show increased extracellular regulated protein kinase 1/2 (ERK1/2) and reduced aortic relaxation.
Purpose of the Study:
- To investigate the effect of PD98059, an ERK1/2 inhibitor, on aortic function and DM MPs.
- To determine if PD98059 can mitigate the negative vascular effects of DM MPs.
Main Methods:
- Induction of diabetes in mice using streptozotocin.
- Isolation and characterization of MPs from control, diabetic, and PD98059-treated diabetic mice.
- Assessment of vascular function in isolated aortas and in response to MP treatment.
- Analysis of ERK1/2 phosphorylation and intracellular adhesion molecule-1 (ICAM-1) expression.
Main Results:
- PD98059 treatment significantly reduced ERK1/2 phosphorylation in DM MPs.
- Endothelium-dependent vascular function was impaired in DM aortas and DM MPs, but improved with PD98059 treatment.
- DM MPs increased ERK1/2 and ICAM-1 expression in aortas, effects mitigated by PD98059 treatment.
Conclusions:
- PD98059 treatment improves endothelial dysfunction in diabetic mice.
- The adhesion properties of DM MPs can be partially blocked by PD98059 through inhibition of ERK and ICAM-1 pathways.
- These findings suggest a potential therapeutic strategy targeting ERK and ICAM-1 to manage vascular complications in diabetes.
