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Published on: October 12, 2017
Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease
Jun Su1, Xiang Hua, Max Vikström
1Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, 17177 Stockholm, Sweden.
Insights
Antibodies against oxidized cardiolipin (aOxCL) show a dual role in cardiovascular disease (CVD) risk. Low levels of IgM aOxCL increase CVD risk, while high levels of IgM and IgG aOxCL are protective.
Area of Science:
- Immunology
- Cardiovascular Disease Research
- Oxidative Stress Biology
Background:
- Antibodies against cardiolipin (aCL) are linked to cardiovascular disease (CVD) risk.
- The role of antibodies against oxidized cardiolipin (aOxCL) in CVD remains to be elucidated.
Purpose of the Study:
- To investigate the association between antibodies against oxidized cardiolipin (aOxCL) and incident cardiovascular disease (CVD).
- To determine if aOxCL levels correlate with CVD risk factors and outcomes.
Main Methods:
- A prospective study of 4132 individuals (2039 men, 2193 women) aged sixty years from Stockholm County.
- Measurement of aOxCL and antibodies against cardiolipin (aCL) using ELISA.
- Assessment of oxidized low-density lipoprotein (oxLDL) uptake in macrophages via flow cytometry (FACScan).
Main Results:
- Lower levels of IgM aOxCL were observed in CVD cases compared to controls.
- The lowest quartile of IgM aOxCL was associated with an increased risk of CVD (OR: 1.80), particularly in men for CVD and stroke.
- High levels of IgM and IgG aOxCL were associated with a decreased risk of CVD (OR: 0.485 and 0.23, respectively).
- aCL were not associated with CVD.
- Oxidized cardiolipin (oxCL) competed with oxLDL for uptake in macrophages, and aOxCL recognized oxCL but not CL.
Conclusions:
- Antibodies against oxidized cardiolipin (aOxCL) represent a novel risk and protective marker for cardiovascular disease (CVD).
- The findings suggest potential therapeutic implications related to macrophage uptake of oxCL and oxLDL.
- Further research is warranted to explore how aOxCL may interfere with oxCL and oxLDL interactions in macrophages.
Background:
Antibodies against cardiolipin (aCL) are associated with increased risk of cardiovascular disease (CVD). We here determine the role of antibodies against oxidized CL (aOxCL).
Methods:
One third of sixty-year olds from the Stockholm County were screened (2039 men, 2193 women), where 211 incident CVD-cases and 633 age- and sex-matched controls were identified (5-7 year follow-up). Antibodies were determined by ELISA and uptake of oxLDL in macrophages by FACScan.
Results:
IgM aOxCL was lower among CVD cases than controls (p=0.024). aOxCL-levels were divided in quartiles with the highest quartile set as the reference group. After adjustment for smoking, BMI, type II diabetes, hypercholesterolaemia and hypertension, an increased risk was determined in the lowest quartile of IgM aOxCL (OR: 1.80, CI: 1.12-2.91, p=0.0159); OR for men in the lowest quartile was 2.46 (CI 1.34-4.53, p=0.0037) for CVD and for stroke: 12.28 (CI: 1.48-101.77, p=0.02). IgG aOxCL levels did not differ between quartiles in CVD-risk. High levels of IgM aOxCL (reaching significance above 86th) and IgG aOxCL (above 95th percentile) were associated with decreased risk of CVD (OR: 0.485, CI: 0.283-0.829; p=0.0082 and OR: 0.23, CI: 0.07-0.69; p=0.0091). aCL were not associated with CVD. oxCL but not CL competed out uptake of OxLDL in macrophages, and aOxLDL recognized oxCL but not CL. In contrast to aCL, aOxCL was not dependent on co-factor Beta2-glycoprotein-I.
Conclusions:
aOxCL is a novel risk/protection marker for CVD, with therapeutic implications. OxCL competes with oxLDL for uptake in macrophages and the possibility that aOxCL inhibits such uptake by interfering with same or similar epitopes in oxCL and oxLDL should be further studied.
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