Complement activation in hypercholesterolemia

Background and Aim: inflammatory and lipid factors share an important role in atherosclerosis. This study evaluates their relations in dyslipidemic su bjects. Methods and Results: We compared the complement system (serum hemolytic act ivity CH50, C3 and C4 fractions and terminal complex sC5b-9) in 30 hypercho lesrerolemic patients with elevated cholesterol and decreased HDL-cholester ol levels, 30 normolipemic patients with clinical atherosclerosis and 30 ma tched normal subjects. In addition we evaluated the circulating immune comp lexes containing cholesterol (chol-CIC) on the assumption that they might b e important in complement activation, and the circulating levels of the adh esion molecule ICAM-1 (slCAM-1) as a sign of endhotelial dysfunction. We fo und a significant increase of sC5b-9 (but not of CH50 anti C3, C4) in the h ypercholesterolemics compared with the other groups. The plasma sC5b-9 leve l Il,as inversely and significantly related to HDL-chol (regression analysi s), whereas no direct significant relation was found between sC5b-9 and cho lesterol. Chol-CIC were also significantly increased in this group. The ath erosclerosis patients also presented a significant increase of sC5b-9. Last ly, both patient groups displayed a significant increase of slCAM-1. Conclusions: We suggest that complement activation in dyslipidemics may be induced by their increased immune complexes. However, the decrease of compl ement 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 i s suggested in our study by the changes of sICAM-1. (C) 2000, Medikal Press .