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Growth differentiation factor 15 in adverse cardiac remodelling: from biomarker to causal player
Marian Wesseling1,2, Julius H C de Poel1, Saskia C A de Jager1,3
1Laboratory for Experimental Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Insights
Growth Differentiation Factor 15 (GDF15) shows prognostic value in heart failure, but its exact biological role in cardiac remodeling requires further investigation for biomarker and therapeutic use.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Heart failure is a growing global health concern due to increased survival post-myocardial infarction, lifestyle factors, and an aging population.
- The complexity of heart failure pathology hinders diagnosis and treatment, creating a need for effective biomarkers.
- Growth Differentiation Factor 15 (GDF15) is recognized as a biomarker in various diseases, including cardiovascular conditions, with established prognostic value in heart failure.
Purpose of the Study:
- To review the current understanding of GDF15's biological functions in the context of heart failure.
- To explore the role of GDF15 in intracellular and extracellular processes contributing to adverse cardiac remodeling.
- To identify key considerations for integrating GDF15 as a clinical biomarker or therapeutic target.
Main Methods:
- Literature review of studies investigating GDF15 in heart failure.
- Analysis of GDF15's involvement in cellular pathways such as inflammation, cell cycle, apoptosis, fibrosis, hypertrophy, and endothelial dysfunction.
- Synthesis of information regarding GDF15's pleiotropic nature and its implications in complex disease processes.
Main Results:
- GDF15 is a pleiotropic protein implicated in various biological processes relevant to heart failure.
- Evidence suggests GDF15 plays a role in fibrosis, hypertrophy, and endothelial dysfunction, contributing to adverse cardiac remodeling.
- While GDF15's prognostic value in heart failure is robust, its precise functional mechanisms remain incompletely understood.
Conclusions:
- Further research is essential to fully elucidate GDF15's complex biological functions in heart failure pathogenesis.
- Understanding GDF15's exact role is critical before its widespread adoption as a standard diagnostic biomarker or for therapeutic interventions.
- GDF15 represents a promising area for biomarker discovery and potential therapeutic strategies in managing heart failure.
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.
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