Aims 
Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-ß superfamily (TGF-ß), is involved in cardiovascular disease, inflammation and development of atherosclerosis and is highly expressed in macrophages (MΦ) of atherosclerotic lesions. Moreover, an indication exists regarding its involvement in arteriosclerotic processes. Thus, we were interested to investigate the regulatory effect of GDF-15 on autophagy in human MΦ during foam cell formation. 

Methods and Results
Modified oxidized-low density lipoprotein (oxLDL), recombinant (r)GDF-15, plus transiently silenced GDF-15 (siGDF-15 MΦ) and negative siRNA transfected (nsiGDF-15 MΦ) PMA-differentiated human THP-1 MΦ were used to investigate the effects of GDF-15 on autophagic processes. Foam cell formation was determined by Oil Red O staining, which revealed that rGDF-15 alone, but also in combination with oxLDL significantly increased the lipid accumulation in THP-1 MΦ. Vice versa in siGDF-15 MΦ, the lipid accumulation was decreased compared to nsiGDF-15 MΦ. Western-blot analyses and confocal laser scanning microscopy showed an increase of Atg5 and p62 protein in THP-1 MΦ co-incubated with rGDF-15 and oxLDL, as well as an increase of the p62-accumulation compared to rGDF-15-treated MΦ. Interestingly rGDF-15 increased the autophagic activity whereas oxLDL decreased the autophagic activity compared to medium control. Vice versa, siGDF-15 MΦ showed a reduced p62-accumulation and autophagic acitivity compared to nsiGDF-15 MΦ. The present study indicates that GDF-15, especially in combination with oxLDL regulates the expression of autophagy-relevant proteins and the p62-accumulation in human MΦ. 

Conclusion
GDF-15 affects autophagic processes in human MΦ. This study may indicate anovel important pathophysiological role of GDF-15 on atherosclerotic plaque development and progression.

06 - GROWTH DIFFERENTIATION FACTOR-15 (GDF-15) REGULATES AUTOPHAGIC PROCESSES IN OXLDL-TREATED HUMAN MACROPHAGES