Complement system is activated in stenotic aortic valves.

Area of Science:

• Immunology
• Cardiovascular Biology
• Pathology

Background:

• Aortic valve stenosis (AS) is a progressive condition often associated with inflammation.
• The complement system, a crucial inflammatory mediator, has not been fully elucidated in AS pathogenesis.

Purpose of the Study:

• To investigate the role of the complement system in the development and progression of aortic valve stenosis.

Main Methods:

• Immunohistochemistry and RT-PCR were used to analyze complement component C5b-9 and anaphylatoxin receptors (C3aR, C5aR) in human aortic valve tissues.
• Valve myofibroblasts were isolated and stimulated with inflammatory factors (TNF-alpha, cigarette smoke) and C3a to assess receptor expression and cytokine secretion.

Main Results:

• Complement complex C5b-9 deposition was observed in early and advanced AS lesions.
• Upregulated expression of C3aR and C5aR was detected in stenotic valves, particularly on myofibroblasts.
• Cigarette smoke and TNF-alpha increased C3aR expression in myofibroblasts, which, upon C3a stimulation, secreted increased levels of pro-inflammatory cytokines (MCP-1, IL-6, IL-8).

Conclusions:

• Complement activation is a significant factor in the inflammatory process of aortic valve stenosis.
• Inflammation and risk factors like cigarette smoke upregulate complement receptors on valve myofibroblasts, contributing to AS.
• Targeting the complement system presents a novel therapeutic strategy for aortic valve stenosis.