Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization

Area of Science:

• Ophthalmology
• Vascular Biology
• Immunology

Background:

• Chemerin is a protein known for its role in leukocyte attraction and previously identified as an anti-tumoral factor inhibiting vascularization.
• Its primary functional receptor is Chemokine Like Receptor 1 (CMKLR1).

Purpose of the Study:

• To investigate the role of chemerin in regulating vascular network density and angiogenesis.
• To elucidate the mechanism underlying chemerin's effect on vascular development and regression.

Main Methods:

• Overexpression of bioactive chemerin in mice to assess its impact on retinal vascular networks.
• Utilizing CMKLR1-deficient mice to determine receptor involvement.
• Assessing chemerin's effect on neoangiogenesis in models of retinopathy and hind-limb ischemia.
• Investigating the involvement of the PI3-kinase/AKT pathway using PTEN and FOXO1 antagonists.

Main Results:

• Overexpression of chemerin reduced retinal vascular network density in developing and adult mice.
• Chemerin promoted endothelial cell apoptosis and vessel pruning, but not vascular sprouting.
• The observed vascular phenotype was normalized in CMKLR1-deficient mice.
• Chemerin inhibited neoangiogenesis in pathological retinopathy and hind-limb ischemia models.
• PTEN and FOXO1 antagonists partially restored retinal vasculature density, indicating PI3-kinase/AKT pathway involvement.

Conclusions:

• Chemerin, acting via CMKLR1, plays a significant role in regulating vascular network homeostasis by inducing endothelial cell apoptosis and vessel regression.
• The PI3-kinase/AKT pathway is implicated in chemerin-mediated vascular remodeling.
• These findings suggest potential therapeutic implications for conditions involving aberrant angiogenesis.