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Published on: January 29, 2014
Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic
Ying Xin1, Elisabeth Hertle1, Carla J H van der Kallen1
1Department of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Insights
Complement components C3 and C4 are linked to the development of metabolic syndrome. Higher levels of C3 and C4 were observed in individuals with metabolic syndrome, suggesting their role in disease progression.
Area of Science:
- Immunology
- Metabolic Diseases
- Cardiovascular Health
Background:
- The complement system, a crucial part of innate immunity, plays a role in inflammation and metabolic processes.
- Dysregulation of the complement pathway has been implicated in various cardiometabolic diseases.
- Understanding the specific roles of complement components in metabolic syndrome is essential for developing targeted therapies.
Purpose of the Study:
- To investigate the association between components of the alternative and classical complement pathways and prevalent and incident metabolic syndrome.
- To identify specific complement factors that may serve as biomarkers or therapeutic targets for metabolic syndrome.
Main Methods:
- A cohort study of 574 participants with a moderately increased risk of cardiometabolic disease was conducted.
- Plasma levels of complement components were measured at baseline.
- Multiple logistic regression analyses were used to assess associations with prevalent and incident metabolic syndrome over a 7-year follow-up period.
Main Results:
- Higher levels of C3 and C4 were significantly associated with prevalent metabolic syndrome in cross-sectional analyses.
- C3 and C4 were also associated with incident metabolic syndrome, indicating a role in disease development.
- No significant associations were found for other complement components, including regulators and activated products, with incident metabolic syndrome.
Conclusions:
- C3 and C4, but not their regulators or activated products, are associated with the development of metabolic syndrome.
- These findings highlight the specific roles of C3 and C4 in the pathogenesis of metabolic syndrome.
- Further research is warranted to explore the therapeutic potential of targeting C3 and C4 in metabolic syndrome.
Purpose:
We investigated the associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], properdin) and the classical complement pathway (C4, C1q, C1-inhibitor [C1-INH]) with prevalent and incident metabolic syndrome in a cohort with a moderately increased risk of cardiometabolic disease.
Methods:
The study cohort was comprised of 574 participants (61% men, age 59.6 ± 7.0 years) at baseline and 489 participants after 7-year follow-up. Multiple logistic regression analyses were done to investigate the associations of concentrations of baseline plasma complement (standardized values) with prevalent and incident (in those without metabolic syndrome at baseline, n = 189) metabolic syndrome.
Results:
C3 (odds ratio (OR) = 1.48 [95% confidence interval: 1.02; 2.14]) and C4 (OR = 1.95 [1.32; 2.88]), but none of the other complement components were associated with incident metabolic syndrome (n = 40 cases). Notably, in the cross-sectional analyses, we did observe higher levels of C3a (OR = 1.25 [1.03; 1.52]), FH (OR = 2.93 [2.24; 3.83]), and properdin (OR = 1.88 [1.50; 2.34]), in addition to C3 (OR = 3.60 [2.73; 4.75]) and C4 (OR = 1.39 [1.13; 1.69]), in those with the metabolic syndrome compared to those without, while no association was observed for FD, Bb, C1q, or C1-INH.
Conclusions:
In the cross-sectional analyses, the effects sizes (standardized regression coefficients) for C3 and C4 were similar to those of (some of) the regulators and activators, yet only C3 and C4 were associated with incident disease. These findings suggest a role for C3 and C4, but not their regulators or activated products, in the development of the metabolic syndrome.
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