Complement C6 deficiency protects against diet-induced atherosclerosis in rabbits

Area of Science:

• Immunology
• Cardiovascular Research
• Atherosclerosis

Background:

• Low-density lipoprotein (LDL) can become atherogenic through enzymatic degradation.
• Enzymatically degraded LDL triggers macrophage foam cell formation, cytokine release, and complement activation.

Purpose of the Study:

• To investigate the role of complement activation in the development of atherosclerosis.
• To determine if complement component 6 (C6) deficiency protects against diet-induced atherosclerosis.

Main Methods:

• Used 6 pairs of homozygous C6-deficient rabbits and heterozygous siblings fed a cholesterol-rich diet for 14 weeks.
• Analyzed cholesterol levels, plasma lipoprotein profiles, and atherosclerotic plaque formation.
• Quantified lesions and lumen stenosis using computer-based morphometry on stained aortic sections.

Main Results:

• No significant differences in cholesterol levels or lipoprotein profiles between C6-deficient and C6-competent rabbits.
• Extensive aortic lesions observed in all C6-competent rabbits.
• Complete absence of aortic lesions in all C6-deficient rabbits, demonstrating a protective effect.

Conclusions:

• The terminal complement sequence plays a central role in the progression of atherosclerotic lesions.
• C6 deficiency significantly protects against diet-induced atherosclerosis.