C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study

Area of Science:

• Cardiovascular Research
• Immunology
• Lipid Metabolism

Background:

• Plasma lipoproteins have heterogeneous subclasses.
• Complement system associations with lipids are primarily studied for major lipid classes.
• Complement's impact on lipoprotein subclass characteristics is largely unknown.

Purpose of the Study:

• To investigate associations between alternative complement pathway components and plasma lipoprotein subclass profiles.
• To determine the role of complement component 3 (C3) and other factors in lipoprotein subclass characteristics.

Main Methods:

• Utilized data from 523 participants in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study.
• Measured plasma complement concentrations (C3, properdin, factor H, factor D, MASP-3, C3a, Bb) and lipoprotein subclass profiles via NMR spectroscopy.
• Employed multiple linear regression to analyze associations between C3 and other complement components with lipoprotein subclass particle concentration, size, and lipid content.

Main Results:

• Higher C3 concentrations were associated with increased VLDL, IDL, LDL, and small HDL particles.
• Elevated C3 levels correlated with fewer very large and large HDL particles.
• All lipoprotein subclasses showed triglyceride enrichment in individuals with higher C3 concentrations. Similar associations were found for properdin, factor H, factor D, and MASP-3, but not C3a and Bb.

Conclusions:

• The alternative complement pathway, especially C3, is linked to an adverse lipoprotein subclass profile.
• This adverse profile is characterized by an increase in triglyceride-enriched lipoproteins.
• A decrease in large HDL particles was also observed in association with higher C3 levels.