Activation of the human terminal complement pathway in atherosclerosis

Area of Science:

• Immunology
• Pathology
• Cardiovascular Research

Background:

• The terminal C5b-9 complement complex signifies in situ complement activation, leading to tissue damage and inflammation.
• Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.

Purpose of the Study:

• To investigate the presence and localization of terminal complement complex (C5b-9) and related proteins in various stages of human atherosclerotic lesions.
• To determine the association of complement deposition with the progression of atherosclerosis.

Main Methods:

• Indirect and double-staining immunoperoxidase techniques were employed.
• Localization of C5b-9 neoantigens, S protein, C3c, C3d, and apolipoprotein B was performed.
• Samples included aortic and coronary artery plaques and intimal thickenings, as well as femoral fibrous plaques.

Main Results:

• Terminal C5b-9, S protein, C3c, C3d, and apolipoprotein B deposits were found in aortic fibrous plaques, intimal thickenings, fatty streaks, coronary fibrous plaques, coronary intimal thickenings, and femoral fibrous plaques.
• These deposits were observed from early to advanced stages of atherosclerosis.
• The presence of deposits correlated with the degree of fibrosis and necrosis within the lesions.

Conclusions:

• Complement activation and deposition, evidenced by C5b-9 complex formation, occur in situ within atherosclerotic lesions.
• The localization patterns suggest local assembly of the C5b-9 complex.
• Complement activation may play a sustained role in the chronic progression of atherosclerosis.