Platelet-released phospholipids link haemostasis and angiogenesis.

Area of Science:

• Biochemistry
• Cell Biology
• Vascular Biology

Background:

• Angiogenesis mediators at injury sites are less defined than those in abnormal growth.
• Blood coagulation (hemostasis) factors are potential candidates for wound repair angiogenesis.
• Platelet-derived lipid mediators are increasingly recognized for their role in angiogenesis.

Purpose of the Study:

• To investigate the role of platelet-derived lipid mediators in angiogenesis during wound repair.
• To identify specific lipid mediators involved in endothelial cell responses crucial for angiogenesis.
• To establish the link between hemostasis and angiogenesis mediated by platelet factors.

Main Methods:

• Identification of lipid mediators acting on G-protein coupled EDG receptors.
• Cloning of EDG-1 receptor expressed by angiogenic endothelial cells.
• Assessing endothelial cell responses (migration, proliferation, morphogenesis) to lipid mediators like SPP, LPA, and PA.
• Quantifying chemoattractive activity in serum generated during clotting.

Main Results:

• Sphingosine 1-phosphate (SPP), lysophosphatidate (LPA), and phosphatidic acid (PA) are agonists for EDG receptors on endothelial cells.
• SPP, LPA, and PA induce key endothelial cell behaviors essential for angiogenesis.
• >80% of serum chemoattractive activity during clotting is due to platelet-derived SPP.
• Platelet-derived lipid mediators significantly contribute to the angiogenic response.

Conclusions:

• Platelet-derived sphingosine 1-phosphate (SPP) is a major contributor to the pro-angiogenic activity generated during blood clotting.
• Lipid mediators like SPP, LPA, and PA play critical roles in endothelial cell responses necessary for wound repair angiogenesis.
• These findings establish a novel connection between hemostasis and angiogenesis mediated by platelet-derived lipid factors.