Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation
Zhenjiu Zhu1, Chenglai Fu, Xiaoxia Li
1Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Plos One
|August 31, 2011
Summary
Prostaglandin E2 (PGE2) enhances new blood vessel formation by promoting bone marrow-derived cell differentiation and migration via the EP4 receptor and AMP-activated protein kinase (AMPK). This pathway holds potential for treating ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Angiogenesis Research
Background:
- Prostaglandin E2 (PGE2) is known to influence angiogenesis, the formation of new blood vessels.
- Endothelial progenitor cells, derived from bone marrow, can differentiate into endothelial cells.
- The precise mechanisms of PGE2's effects on bone marrow-derived cells (BMCs) in angiogenesis remain unclear.
Purpose of the Study:
- To elucidate the mechanism by which PGE2 stimulates bone marrow-derived cells (BMCs) in angiogenesis.
- To identify the specific receptors and signaling pathways involved in PGE2-mediated BMC function.
- To assess the therapeutic potential of PGE2 in ischemic conditions.
Main Methods:
- Treatment of BMCs with PGE2 and assessment of differentiation and migration markers (CD31, von Willebrand factor, MMP-2, MMP-9).
- Investigation of the role of AMP-activated protein kinase (AMPK) using dominant-negative and inhibitor approaches.
- Analysis of EP receptor involvement (EP1, EP2, EP3, EP4) using blocking peptides and agonists.
- Evaluation of neovascularization in EP4(+/-) mice and assessment of AMPK and endothelial nitric oxide synthase (eNOS) phosphorylation.
Main Results:
- PGE2 significantly increased BMC differentiation, migration, and tube formation.
- Upregulation of differentiation and migration markers was dependent on AMP-activated protein kinase (AMPK) activation.
- PGE2's pro-angiogenic effects were mediated through the EP4 receptor, leading to AMPK activation and subsequent eNOS phosphorylation.
- Blocking EP4 or using EP4(+/-) mice attenuated the pro-angiogenic effects of PGE2.
Conclusions:
- PGE2 promotes neovascularization by enhancing BMC differentiation and migration through the EP4 receptor in an AMPK-dependent pathway.
- The findings highlight a novel mechanism for PGE2 in regulating angiogenesis.
- PGE2 demonstrates potential clinical utility in managing ischemic heart disease.
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