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C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study
Ying Xin1, Elisabeth Hertle2, Carla J H van der Kallen2
1Department of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, the Netherlands; Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Insights
The alternative complement pathway, particularly complement component 3 (C3), is linked to an unfavorable lipoprotein profile. Higher C3 levels correlate with increased triglyceride-rich lipoproteins and decreased large HDL particles.
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.
Background:
Plasma lipoproteins contain heterogeneous subclasses. Previous studies on the associations of the complement system with lipids and lipoproteins are mainly limited to the major lipid classes, and associations of complement with lipoprotein subclass characteristics remain unknown.
Objective:
We investigated the associations of C3 and other components of the alternative complement pathway with plasma lipoprotein subclass profile.
Methods:
Plasma complement concentrations (complement component 3 [C3], properdin, factor H, factor D, MASP-3, C3a, Bb), and lipoprotein subclass profile (as measured by nuclear magnetic resonance spectroscopy) were obtained in 523 participants (59.6 ± 6.9 years, 60.8% men) of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study. Multiple linear regression was used to investigate the associations of C3 (primary determinant) and other alternative pathway components (secondary determinants) with characteristics (particle concentration and size [main outcomes], and lipid contents [secondary outcomes]) of 14 lipoprotein subclasses, ranging from extremely large VLDL to small HDL (all standardized [std] values).
Results:
Participants with higher C3 concentrations had more circulating VLDL (stdβs ranging from 0.27 to 0.36), IDL and LDL (stdβs ranging from 0.14 to 0.17), and small HDL (stdβ = 0.21). In contrast, they had fewer very large and large HDL particles (stdβs = -0.36). In persons with higher C3 concentrations, all lipoprotein subclasses were enriched in triglycerides. Similar but weaker associations were observed for properdin, factor H, factor D, and MASP-3, but not for C3a and Bb.
Conclusions:
The alternative complement pathway, and most prominently C3, is associated with an adverse lipoprotein subclass profile that is characterized by more triglyceride-enriched lipoproteins but fewer large HDL.
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