Growth differentiation factor-15 regulates oxLDL-induced lipid homeostasis and autophagy in human macrophages

Growth differentiation factor-15 (GDF-15), a divergent and distant member of the transforming growth factor-{beta} superfamily, is suggested as a risk factor for cardiovascular diseases. Thus, we are interested to investigate the influence of GDF-15 in lipid homeostasis and autophagy in macrophages (M{Phi}) during foam cell formation. Our investigations represent the impairment of GDF-15 on modulators of autophagy and lipid homeostasis in PMA-differentiated human THP-1 M{Phi}. In this context, in vitro resulted GDF-15 silencing in a reduction of lipid accumulation, whereas the addition of recombinant (r)GDF-15 increased the lipid accumulation in human M{Phi} independent of oxidized (ox)LDL. Additionally, GDF-15 affected the expression of autophagy-relevant proteins (p62, Atg5 and Atg12/Atg5 protein complex) and the p62 accumulation in THP-1 M{Phi}. Hence, our data suggest that GDF-15 is involved in the regulation of the lipid homoeostasis of human M{Phi} by regulating autophagic processes.