Atherosclerotic dyslipidemia revealed by plasma lipidomics on ApoE-/- mice fed a high-fat diet.

BACKGROUND AND AIMS: The pathological process of atherosclerosis is closely related to lipid accumulation at arterial wall caused by lipoproteins transporting lipids through blood. In this study, we investigate the lipid composition in the plasma of apolipoprotein E deficient (ApoE-/-) mice fed a high-fat diet to reveal atherosclerosis-induced dyslipidemia.

METHODS

ApoE-/- and corresponding wild-type C57BL/6J mice were used as the pathology model and control, respectively, and were fed a high-fat or normal diet. Lipidomics approach based on chromatography coupled with time of fight mass spectrometry (UPLC-Q/TOF-MS) was applied to profile lipid species.

RESULTS

Discrimination analysis revealed that 1 lysophosphatidylcholine (LPC) and 6 phosphatidylcholines (PCs) were identified to distinguish C57BL/6J mice fed a normal and high-fat diet. PC (16:0/18:1) and PC (18:0/18:1) were also extracted when the comparison was done between ApoE-/- and C57BL/6J mice, both fed a high-fat diet. Besides the 2 PCs, the other 4 PCs, 1 sphinganine (SP) and 3 sphingomyelins (SMs) were identified in the second comparing case, among which PC (16:0/16:0), PC (18:0/16:1), SM (d16:0/28:5), SM (d18:1/24:1) and SM (d18:1/16:0) showed obviously positive correlations with the plasma levels of TC and LDL-C. However, no significant relationship was observed between the differential lipids and TG or HDL-C.

CONCLUSIONS

This study reveals that SP, SMs and PCs are the particularly changed lipid species induced by atherosclerotic lesions in the ApoE-/- model, indicating a disturbance on sphingolipid and glycerophospholipid metabolism during the progression of atherosclerotic dyslipidemia.