Growth differentiation factor-15 and cardiovascular dysfunction and disease: malefactor or innocent bystander?

It is widely recognized that around 20% of cardiovascular events occurring in the general population cannot be inferred from conventional risk factors.1 This led to a growing interest in novel measurable humoral biomarkers, hopefully leading to an improvement of global cardiovascular risk stratification. Growth differentiation factor-15 (GDF-15) is the latest promising marker in this field. Growth differentiation factor-15 is a protein belonging to the transforming growth factor-β (TGF-β) superfamily, which includes more than 40 proteins with crucial functions in adult tissue homeostasis by modulating cell survival, proliferation, differentiation, and tissue repair in different organs. Initially cloned from an activated macrophage cell line, GDF-15 has been proposed as a cell death promoter in several tumour cell lines, highlighting its potential role as an inductor of apoptosis in some cancer cells.2 Expression of GDF-15 is rapidly induced by IL-1, TNF-α, and TGF-β in macrophages, thereby limiting macrophage activation and inflammation.3 Results of analysis from human tissues evidenced the presence of GDF-15 also in the kidney, prostate and placenta, breast and colon, as well as in the heart.3