The role of complement activation in atherosclerosis

Area of Science:

• Immunology
• Cardiovascular Medicine
• Pathogenesis of Atherosclerosis

Background:

• Atherosclerosis is a chronic inflammatory disease involving dyslipidemia, inflammation, and immune responses.
• Monocytes/macrophages, complement system, and T-lymphocytes are implicated in atherogenesis.
• Complement activation and C5b-9 deposition are observed in human and experimental atherosclerosis.

Purpose of the Study:

• To investigate the role of the complement system, particularly C5b-9, in the development and progression of atherosclerotic lesions.
• To determine if complement activation is essential for the maturation of atherosclerotic plaques.

Main Methods:

• Review of existing literature on complement system involvement in atherosclerosis.
• Analysis of studies investigating the effects of complement C6 deficiency on diet-induced atherosclerosis.
• Examination of the impact of C5b-9 deposition on cellular processes within atherosclerotic lesions.

Main Results:

• Complement C6 deficiency demonstrates a protective effect against diet-induced atherosclerosis, highlighting the necessity of C5b-9 assembly for lesion progression.
• The maturation of atherosclerotic lesions beyond the foam cell stage is dependent on an intact complement system.
• Sublytic C5b-9 assembly induces activation and proliferation of smooth muscle cells (SMC) and endothelial cells (EC), and may cause cell lysis.

Conclusions:

• Complement system activation plays a significant role in atherogenesis.
• C5b-9 assembly is critical for the progression of atherosclerotic lesions.
• Targeting complement activation may represent a therapeutic strategy for atherosclerosis.