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Complement activation in hypercholesterolemia
A L Pasqui1, G Bova, L Puccetti
1Department of Internal Medicine and Immunology, University of Siena, Italy.
Insights
Complement activation, indicated by increased sC5b-9, is linked to dyslipidemia and atherosclerosis. This may be driven by cholesterol immune complexes and reduced HDL, affecting endothelial function.
Area of Science:
- Immunology
- Cardiovascular Science
- Biochemistry
Background:
- Atherosclerosis involves both inflammatory and lipid factors.
- Dyslipidemia is a key risk factor for cardiovascular disease.
Purpose of the Study:
- To investigate the relationship between lipid profiles, complement system activation, and endothelial dysfunction in dyslipidemic subjects.
- To explore the role of cholesterol-containing immune complexes (chol-CIC) and soluble intercellular adhesion molecule-1 (sICAM-1) in this process.
Main Methods:
- Comparison of complement system components (CH50, C3, C4, sC5b-9), chol-CIC, and sICAM-1 levels in hypercholesterolemic patients, patients with clinical atherosclerosis, and normal subjects.
- Regression analysis to determine relationships between sC5b-9, HDL-cholesterol, and total cholesterol.
Main Results:
- Significantly elevated terminal complement complex (sC5b-9) in hypercholesterolemic and atherosclerosis patients compared to controls.
- Inverse correlation between plasma sC5b-9 and HDL-cholesterol levels.
- Increased chol-CIC and sICAM-1 in patient groups, suggesting immune complex involvement and endothelial dysfunction.
Conclusions:
- Complement activation in dyslipidemia may be triggered by increased immune complexes.
- Reduced levels of complement regulatory proteins on HDL contribute to complement activation.
- Complement system alterations are linked to endothelial dysfunction and potentially other systemic factors.
Background And Aim:
Inflammatory and lipid factors share an important role in atherosclerosis. This study evaluates their relations in dyslipidemic subjects.
Methods And Results:
We compared the complement system (serum hemolytic activity CH50, C3 and C4 fractions and terminal complex sC5b-9) in 30 hypercholesterolemic patients with elevated cholesterol and decreased HDL-cholesterol levels, 30 normolipemic patients with clinical atherosclerosis and 30 matched normal subjects. In addition we evaluated the circulating immune complexes containing cholesterol (chol-CIC) on the assumption that they might be important in complement activation, and the circulating levels of the adhesion molecule ICAM-1 (sICAM-1) as a sign of endhotelial dysfunction. We found a significant increase of sC5b-9 (but not of CH50 and C3, C4) in the hypercholesterolemics compared with the other groups. The plasma sC5b-9 level was inversely and significantly related to HDL-chol (regression analysis), whereas no direct significant relation was found between sC5b-9 and cholesterol. Chol-CIC were also significantly increased in this group. The atherosclerosis patients also presented a significant increase of sC5b-9. Lastly, both patient groups displayed a significant increase of sICAM-1.
Conclusions:
We suggest that complement activation in dyslipidemics may be induced by their increased immune complexes. However, the decrease of complement regulatory proteins carried by HDL is another important factor, while complement changes may be related to variations of other humoral and cell systems (endothelium, coagulative/fibrinolytic system), whose involvement is suggested in our study by the changes of sICAM-1.