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Review
. 2020 Aug;7(4):1488-1501.
doi: 10.1002/ehf2.12728. Epub 2020 May 18.

Growth differentiation factor 15 in adverse cardiac remodelling: from biomarker to causal player

Marian Wesseling  1   2 , Julius H C de Poel  1 , Saskia C A de Jager  1   3
Affiliations
Review

Growth differentiation factor 15 in adverse cardiac remodelling: from biomarker to causal player

Marian Wesseling et al. ESC Heart Fail. 2020 Aug.

Abstract

Heart failure is a growing health issue as a negative consequence of improved survival upon myocardial infarction, unhealthy lifestyle, and the ageing of our population. The large and complex pathology underlying heart failure makes diagnosis and especially treatment very difficult. There is an urgent demand for discriminative biomarkers to aid disease management of heart failure. Studying cellular pathways and pathophysiological mechanisms contributing to disease initiation and progression is crucial for understanding the disease process and will aid to identification of novel biomarkers and potential therapeutic targets. Growth differentiation factor 15 (GDF15) is a proven valuable biomarker for different pathologies, including cancer, type 2 diabetes, and cardiovascular diseases. Although the prognostic value of GDF15 in heart failure is robust, the biological function of GDF15 in adverse cardiac remodelling is not fully understood. GDF15 is a distant member of the transforming growth factor-β family and involved in various biological processes including inflammation, cell cycle, and apoptosis. However, more research is suggesting a role in fibrosis, hypertrophy, and endothelial dysfunction. As GDF15 is a pleiotropic protein, elucidating the exact role of GDF15 in complex disease processes has proven to be a challenge. In this review, we provide an overview of the role GDF15 plays in various intracellular and extracellular processes underlying heart failure, and we touch upon crucial points that need consideration before GDF15 can be integrated as a biomarker in standard care or when considering GDF15 for therapeutic intervention.

Keywords: Adverse cardiac remodelling; Biomarker; Fibrosis; GDF-15; Hypertrophy.

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Figures

Figure 1
Figure 1
Growth differentiation factor 15 (GDF15) transcription and maturation. Originating from two exons, GDF15 is synthesized as polypeptide consisting of a propeptide and a mature region. Between two mature regions, a homodimer is formed by a interchain disulfide bond. The propeptide plays an important role intracellular trafficking and secretion. Pro‐protein convertase subtilisin/kexin types (PCSKs) and matrix metalloproteinases (MMPs) are able to cleave the pro‐GDF15 polypeptide at the RXXR cleave site, thereby forming a biological active mature GDF15. After cleavage, both the propeptide and a mature GDF15 are secreted (figure adapted from Servier Medical Art, https://smart.servier.com/).
See this image and copyright information in PMC

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