TY - JOUR
T1 - C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile
T2 - The CODAM study
AU - Xin, Ying
AU - Hertle, Elisabeth
AU - van der Kallen, Carla J. H.
AU - Vogelzangs, Nicole
AU - Arts, Ilja C. W.
AU - Schalkwijk, Casper G.
AU - Stehouwer, Coen D. A.
AU - van Greevenbroek, Marleen M. J.
N1 - Funding Information:
Part of this work was supported by grants of the Netherlands Organisation for Scientific Research , Netherlands (940-35-034) and the Dutch Diabetes Research Foundation , Netherlands ( 98.901 ) and Dutch Heart Foundation , Netherlands ( NHS2010B194 ); Ying Xin is supported by the Chinese Scholarship Council , China ( 201507040040 ).
Funding Information:
Part of this work was supported by grants of the Netherlands Organisation for Scientific Research, Netherlands (940-35-034) and the Dutch Diabetes Research Foundation, Netherlands (98.901) and Dutch Heart Foundation, Netherlands (NHS2010B194); Ying Xin is supported by the Chinese Scholarship Council, China (201507040040).
Publisher Copyright:
© 2021 National Lipid Association
PY - 2021
Y1 - 2021
N2 - 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 (std beta s ranging from 0.27 to 0.36), IDL and LDL (std beta s ranging from 0.14 to 0.17), and small HDL (stdb = 0.21). In contrast, they had fewer very large and large HDL particles (std beta s = 20.36). 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. (C) 2021 National Lipid Association. Published by Elsevier Inc.
AB - 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 (std beta s ranging from 0.27 to 0.36), IDL and LDL (std beta s ranging from 0.14 to 0.17), and small HDL (stdb = 0.21). In contrast, they had fewer very large and large HDL particles (std beta s = 20.36). 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. (C) 2021 National Lipid Association. Published by Elsevier Inc.
KW - Epidemiology
KW - Human and clinical research
KW - Lipoproteins
KW - Lipidomics
KW - Nuclear magnetic resonance
KW - Lipoprotein composition
KW - Alternative complement
KW - ACYLATION-STIMULATING PROTEIN
KW - MAGNETIC-RESONANCE METABOLOMICS
KW - LOW-DENSITY-LIPOPROTEIN
KW - COMPLEMENT C3
KW - LONGITUDINAL ASSOCIATIONS
KW - ADIPOSE-TISSUE
KW - ACTIVATION
KW - RISK
KW - ATHEROSCLEROSIS
KW - ASP
U2 - 10.1016/j.jacl.2021.01.011
DO - 10.1016/j.jacl.2021.01.011
M3 - Article
C2 - 33612457
SN - 1933-2874
VL - 15
SP - 311
EP - 319
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 2
ER -