C-reactive protein upregulates complement-inhibitory factors in endothelial cells

Area of Science:

• Cardiovascular Science
• Immunology
• Molecular Biology

Background:

• Complement-mediated vascular injury is implicated in atherosclerosis.
• C-reactive protein (CRP) activates the complement cascade.
• Endothelial cells (ECs) express complement-inhibitory factors.

Purpose of the Study:

• To investigate CRP's effect on complement-inhibitory factor expression in ECs.
• To determine if CRP influences protective factors on the endothelial cell surface.

Main Methods:

• Human coronary artery and saphenous vein ECs were incubated with varying concentrations of CRP for up to 72 hours.
• Expression of decay-accelerating factor (DAF), membrane cofactor protein (CD46), and CD59 was quantified using flow cytometry.
• mRNA levels and protein synthesis were assessed to understand the mechanism of CRP-induced changes.

Main Results:

• CRP significantly increased the surface expression of DAF, CD46, and CD59 on ECs.
• CRP-induced upregulation of DAF involved increased mRNA and de novo protein synthesis.
• The enhanced expression of these inhibitors effectively reduced complement-mediated lysis of ECs.

Conclusions:

• CRP upregulates protective complement inhibitors on endothelial cells.
• These findings suggest a potential protective role for CRP in atherogenesis.
• CRP may mitigate complement-mediated vascular damage in the context of atherosclerosis.