Related Experiment Videos
Cardiolipin is a normal component of human plasma lipoproteins
H Deguchi1, J A Fernandez, T M Hackeng
1Departments of Molecular Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Insights
Cardiolipin (CL) is a normal component of human plasma, primarily found in low-density lipoproteins. This finding is crucial for understanding antiphospholipid antibody syndrome and thrombosis risks.
Area of Science:
- Biochemistry
- Immunology
- Hematology
Background:
- Anticardiolipin (anti-CL) antibodies are linked to thrombosis and antiphospholipid antibody syndrome.
- The role of cardiolipin (CL) in plasma and its contribution to these conditions were previously unclear.
Purpose of the Study:
- To investigate the presence and characteristics of cardiolipin (CL) in human plasma.
- To determine the association of CL with lipoproteins and its potential implications for antiphospholipid antibody syndrome.
Main Methods:
- Plasma lipid extracts were analyzed using Thin-Layer Chromatography (TLC), High-Performance Liquid Chromatography (HPLC), and Mass Spectrometry (MS).
- Quantification of CL in fasting plasma samples from 40 individuals (20 males, 20 females).
- Lipoprotein analysis to determine CL distribution.
Main Results:
- Cardiolipin (CL) was identified as a normal component in human plasma, with a mean concentration of 14.9 +/- 3.7 microgram/ml.
- The majority of plasma CL (67%) was found in low-density lipoproteins (LDL), with smaller amounts in high-density lipoproteins (HDL) and very-low-density lipoproteins (VLDL).
- High-density lipoprotein (HDL) showed selective enrichment in CL and phosphatidylethanolamine.
Conclusions:
- Cardiolipin (CL) is a normal constituent of human plasma, predominantly associated with LDL.
- These findings suggest that epitopes of antiphospholipid antibodies may involve CL within lipoproteins or in complexes with plasma proteins or cell surface components.
- This discovery has implications for understanding the pathogenesis of antiphospholipid antibody syndrome and associated thrombotic risks.
Abstract:
Anticardiolipin (anti-CL) antibodies, diagnostic for antiphospholipid antibody syndrome, are associated with increased risks of venous and arterial thrombosis. Because CL selectively enhances activated protein C/protein S-dependent anticoagulant activities in purified systems and because CL is not known to be a normal plasma component, we searched for CL in plasma. Plasma lipid extracts [chloroform/methanol (2:1, vol/vol)] were subjected to analyses by using TLC, analytical HPLC, and MS. A plasma lipid component was purified that was indistinguishable from reference CL (M:1448). When CL in 40 fasting plasma lipid extracts (20 males, 20 females) was quantitated by using HPLC, CL (mean +/- SD) was 14.9 +/- 3.7 microgram/ml (range 9.1 to 24.2) and CL was not correlated with phosphatidylserine (3.8 +/- 1.7 microgram/ml), phosphatidylethanolamine (64 +/- 20 microgram/ml), or choline-containing phospholipid (1,580 +/- 280 microgram/ml). Based on studies of fasting blood donors, CL (>/=94%) was recovered in very low density, low density, and high density lipoproteins (11 +/- 5.3%, 67 +/- 11.0%, and 17 +/- 10%, respectively), showing that the majority of plasma CL (67%) is in low density lipoprotein. Analysis of relative phospholipid contents of lipoproteins indicated that high density lipoprotein is selectively enriched in CL and phosphatidylethanolamine. These results shows that CL is a normal plasma component and suggest that the epitopes of antiphospholipid antibodies could include CL or oxidized CL in lipoproteins or in complexes with plasma proteins (e. g., beta(2)-glycoprotein I, prothrombin, protein C, or protein S) or with platelet or endothelial surface proteins.