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Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways
1Department of Cardiology, Zhongda Hospital, Southeast University; Nanjing, China.
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|September 22, 2009
Summary
Advanced glycation endproducts (AGE) induce endothelial progenitor cell (EPC) apoptosis and reduce nitric oxide (NO) release. These effects are mediated through mitogen-activated protein kinase (MAPK) pathways, highlighting a potential therapeutic target.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Diabetes Pathogenesis
Background:
- Advanced glycation endproducts (AGE) are implicated in diabetic complications.
- AGE-induced endothelial progenitor cell (EPC) apoptosis contributes to diabetes mellitus pathogenesis.
- Nitric oxide (NO) signaling is crucial in regulating apoptosis.
Purpose of the Study:
- To investigate the impact of AGE on human EPC apoptosis and NO release.
- To elucidate the role of mitogen-activated protein kinase (MAPK) pathways in AGE-induced EPC apoptosis.
Main Methods:
- Human EPCs were cultured with varying AGE concentrations and durations.
- EPC apoptosis and NO release were quantified.
- mRNA and protein expression of key apoptotic and signaling molecules (eNOS, COX-2, Bcl-2, Bax, NF-kappaB, Caspase-3) were analyzed.
- MAPK inhibitors were used to assess pathway involvement.
Main Results:
- High AGE concentration (200mg/L) significantly increased EPC apoptosis and decreased NO release in a time-dependent manner.
- AGE exposure altered the expression of eNOS, Bcl-2, COX-2, Bax, NF-kappaB, and Caspase-3.
- MAPK pathway inhibition attenuated AGE-induced EPC apoptosis and molecular changes.
Conclusions:
- AGE promotes EPC apoptosis and reduces NO release.
- The MAPK signaling pathway is a key mediator of AGE's effects on EPCs.
- Targeting MAPK pathways may offer a therapeutic strategy for diabetic vascular complications.
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