C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Cell Death Research

Background:

• Apoptosis is crucial in atherosclerosis, but its regulators remain unclear.
• The role of complement activation, specifically C5b-9, in this process is not well-defined.

Purpose of the Study:

• To investigate the association between apoptotic cells and the terminal complement complex C5b-9 in human atherosclerotic lesions.
• To explore the potential role of complement activation in promoting apoptosis within atherosclerotic plaques.

Main Methods:

• Immunohistochemistry and immunoelectron microscopy were used to detect apoptotic cells (TUNEL, caspase-3, caspase-9, Bax, Bcl-2) and C5b-9 deposits.
• Quantification of apoptotic cells and C5b-9 colocalization across different stages of atherosclerotic lesions (fatty streaks, intimal thickenings, fibrous plaques).

Main Results:

• The apoptotic index increased with lesion severity, being highest in fibrous plaques.
• Bax expression was found in apoptotic cells, while Bcl-2 was rare, indicating mitochondrial pathway involvement.
• C5b-9 deposits colocalized significantly with apoptotic cells, increasing from 2% in fatty streaks to 35% in fibrous plaques.

Conclusions:

• Apoptotic cells in atherosclerotic lesions can harbor C5b-9 deposits.
• Complement activation by apoptotic cells may contribute to apoptosis and the progression of atherosclerosis.