The Complement System Is Essential for Arteriogenesis by Enhancing Sterile Inflammation as a Relevant Step in...

Area of Science:

• Cardiovascular Biology
• Immunology
• Inflammation Research

Background:

• Arteriogenesis is an inflammatory process involving collateral artery growth to bypass occluded arteries.
• The complement system component C3 is a known inflammatory activator.

Purpose of the Study:

• To investigate the role of complement C3 in arteriogenesis using a murine hindlimb model.
• To determine the impact of C3 deficiency on collateral artery growth and associated inflammatory responses.

Main Methods:

• Utilized C3-deficient (C3 -/-) and wildtype mice in a femoral artery ligation model.
• Assessed perfusion recovery using Laser Doppler imaging.
• Analyzed vascular cell proliferation, macrophage recruitment and polarization (CD68+, M1-like), and gene expression (MCP-1) via immunofluorescence and RT-qPCR.

Main Results:

• C3 -/- mice exhibited significantly reduced perfusion recovery and vascular cell proliferation.
• Monocyte chemoattractant protein-1 (MCP-1) expression was significantly lower in C3 -/- mice.
• While total macrophage recruitment was unaffected, C3 deficiency led to a reduction in M1-like polarized macrophages.
• Administration of Compound 48/80 or MCP-1 rescued M1-like macrophage numbers and improved perfusion in C3 -/- mice.

Conclusions:

• Complement C3 plays a critical role in arteriogenesis by promoting MCP-1 expression.
• MCP-1 is essential for inducing and enhancing sterile inflammation required for effective collateral artery growth.
• Targeting the C3-mediated inflammatory pathway could be a therapeutic strategy for improving blood flow in ischemic conditions.