Increased fluidity and oxidation of malarial lipoproteins: relation with severity and induction of endothelial expression of adhesion molecules

Abstract

Introduction: Oxidative stress has been demonstrated in malaria. The potential oxidative modification of lipoproteins derived from malaria patients was studied. These oxidized lipids may have role in pathogenesis of malaria.

Method: The plasma lipid profile and existence of oxidized forms of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were investigated in malaria (17 mild and 24 severe patients) and 37 control subjects. Thiobarbituric acid reactive substances (TBARs), conjugated dienes, tryptophan fluorescence and fluidity of lipoproteins were determined as markers of oxidation. The biological effect of malarial lipoproteins was assessed by the expression of adhesion molecules on endothelial cells.

Results: Malarial lipoproteins had decreased cholesterol (except in VLDL) and phospholipid. The triglyceride levels were unchanged. The cholesterol/phospholipid ratio of LDL was decreased in malaria, but increased in VLDL and HDL. TBARs and conjugate dienes were increased in malarial lipoproteins, while the tryptophan fluorescence was decreased. The fluidity of lipoproteins was increased in malaria. These indicated the presence of oxidized lipoproteins in malaria by which the degree of oxidation was correlated with severity. Of three lipoproteins from malarial patients, LDL displayed the most pronounced oxidative modification. In addition, oxidized LDL from malaria patients increased endothelial expression of adhesion molecules.

Conclusion: In malaria, the lipoproteins are oxidatively modified, and the degree of oxidation is related with severity. Oxidized LDL from malarial patients increases the endothelial expression of adhesion molecules. These suggest the role of oxidized lipoproteins, especially LDL, on the pathogenesis of disease.

Figure 1

Lipoprotein composition in VLDL, LDL and HDL. A: Cholesterol. B: Triglycerides. C: Phospholipid. D. Cholesterol/phospholipid ratio. ^aP < 0.05 and ^bP ≤ 0.001 as compared with normal. Values are mean ± SEM.

Figure 2

Markers of oxidation in lipoproteins. A: TBARs. B: Conjugated dienes. C: Tryptophan fluorescence. ^aP < 0.05 and ^bP ≤ 0.001 as compared with normal. ^cP < 0.05 as compared with mild malaria. Values are mean ± SEM.

Figure 3

Lipoprotein fluidity. A: DPH anisotropy (reciprocal to fluidity). B: Bulk fluidity. C: Annular fluidity. ^aP < 0.05 and ^bP ≤ 0.001 as compared with normal. ^cP < 0.05 as compared with mild malaria. Values are mean ± SEM.

Figure 4

Effect of LDL on HUVEC expression of ICAM-1, VCAM-1 and E-selectin. ^aP < 0.05 and ^bP ≤ 0.001 as compared with normal. ^cP < 0.05 as compared with mild malaria. Values are mean ± SEM.

Figure 5

TBARs levels in media after 24-hours incubation of LDL and HUVEC. ^aP < 0.05 as compared with normal. Values are mean ± SEM.