Fatty acyl composition of lysophosphatidylcholine is important in atherosclerosis

Abstract

Atherosclerosis is a major cause of death for mankind. Although the pathophysiology of atherosclerosis is a complex and multifactorial process, growing body of evidence has identified phospholipids-mediated signaling as an important factor in the induction and progression of atherosclerosis. Lysophosphatidylcholine (LPC) is a major phospholipid in oxidized low-density lipoprotein, and is generally considered to be atherogenic. However, some studies have shown anti-atherogenic properties of LPC. The controversial findings surrounding the pro- or anti-atherogenic properties of LPC appear to be due to the chain length and the degree of saturation of the fatty acyl moiety of LPC. Studies have suggested that the presence of omega (n)-polyunsaturated fatty acids (PUFA) at the sn-1 position of LPC modulates the inflammatory response thereby making LPC anti-atherogenic. We have recently shown that feeding a diet high in n-3 PUFA resulted in the enrichment of LPC in both plasma and liver of C57BL/6 mice with n-3 PUFA. Others have also shown that supplementation with fish oil leads to preferential incorporation of n-3 PUFA into LPC. We also found that plasma obtained from mice fed a diet high in n-3 PUFA showed higher cholesterol efflux capacity compared to animals fed a low n-3 PUFA diet, despite no changes in high-density lipoprotein concentrations. We are therefore hypothesizing that n-3 PUFA enriched LPC has anti-atherogenic properties by promoting cholesterol efflux from macrophages and by reducing inflammation. Our anticipated long term objective is to establish that the fatty acyl moiety of LPC can be used as a potential biomarker for the risk of developing atherosclerosis. Validating this hypothesis would have a substantial impact on the public health with respect to early diagnosis of cardiovascular risks, and designing dietary based therapeutic strategies for the prevention and management of atherosclerosis and other heart related diseases.