A study on the diabetogenic and cardiovascular risk factor apolipoprotein c3(ApoCIII): does it alter the polarisation state of macrophages?

Abstract

Apolipoprotein C3 (ApoCIII) has been heavily associated with promoting inflammatory responses in cardiovascular disease and atherosclerosis. Recently, there has been growing evidence that suggests that ApoCIII is involved in the pathogenesis of diabetes mellitus as well. We suggest that ApoCIII may promote inflammation in the pancreatic islet environment through macrophage polarisation towards a more pro-inflammatory response. In this study, we seek to determine whether ApoCIII is capable of altering the polarization state of macrophages in vitro, using RAW 264.7 macrophages and peritoneal exudate cells (PECs). These cells were stimulated with either lipid A (Lp(a)) or interleukin-4 (IL-4) in the presence or absence of pre-treatment with ApoCIII. Thereafter, the polarisation state of the treated macrophages was determined by RT-qPCR and cytokine release measurement. Our results suggest that ApoCIII pre-treatment alone on RAW 264.7 macrophages may have promoted CCL2 production and release, and may also have decreased the Lp(a)-induction of TNF-α expression in PECs. The lack of an effect of ApoCIII in vitro could also be due to several reasons, namely the time of exposure and concentrations of the stimulants used. Further work is required to comprehensively ascertain if ApoCIII alters the polarisation state of macrophages.