Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor-deficient mice

Area of Science:

• Immunology
• Cardiovascular Biology
• Atherosclerosis Research

Background:

• The classic complement pathway is implicated in inflammatory processes.
• Atherosclerosis is a complex inflammatory disease characterized by plaque buildup in arteries.

Purpose of the Study:

• To investigate the role of the classic complement pathway, specifically C1q, in the development of atherosclerosis.
• To determine if C1q deficiency impacts lesion size and composition in a mouse model of atherosclerosis.

Main Methods:

• Intercrossing C1q-deficient (C1qa-/-) mice with low-density lipoprotein receptor knockout (Ldlr-/-) mice.
• Feeding mice a normal rodent diet and analyzing aortic root lesions at 22 weeks of age.
• Assessing lesion size, cellular composition, C5b-9 deposition, and apoptotic cell presence.

Main Results:

• C1q deficiency significantly increased aortic root lesion size (threefold larger) in Ldlr-/- mice.
• Lesions in C1qa-/-/Ldlr-/- mice exhibited increased vascular smooth muscle cells and abundant apoptotic cells.
• Reduced C5b-9 deposition per lesion unit area in C1qa-/-/Ldlr-/- mice suggested proximal pathway importance.

Conclusions:

• This study provides the first direct evidence for the classic complement pathway's role in atherogenesis.
• Impaired clearance of apoptotic cells, due to C1q deficiency, contributes to larger and more complex atherosclerotic lesions.
• Effective apoptotic cell removal is critical for limiting the progression of early atherosclerotic lesions.