Abstract
Growth and differentiation factor 15 (GDF15) belongs to the transforming growth factor-β (TGF-β) superfamily of proteins. Glial-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL) is an endogenous receptor for GDF15 detected selectively in the brain. GDF15 is not normally expressed in the tissue but is prominently induced by “injury”. Serum levels of GDF15 are also increased by aging and in response to cellular stress and mitochondrial dysfunction. It acts as an inflammatory marker and plays a role in the pathogenesis of cardiovascular diseases, metabolic disorders, and neurodegenerative processes. Identified as a new heart-derived endocrine hormone that regulates body growth, GDF15 has a local cardioprotective role, presumably due to its autocrine/paracrine properties: antioxidative, anti-inflammatory, antiapoptotic. GDF15 expression is highly induced in cardiomyocytes after ischemia/reperfusion and in the heart within hours after myocardial infarction (MI). Recent studies show associations between GDF15, inflammation, and cardiac fibrosis during heart failure and MI. However, the reason for this increase in GDF15 production has not been clearly identified. Experimental and clinical studies support the potential use of GDF15 as a novel therapeutic target (1) by modulating metabolic activity and (2) promoting an adaptive angiogenesis and cardiac regenerative process during cardiovascular diseases. In this review, we comment on new aspects of the biology of GDF15 as a cardiac hormone and show that GDF15 may be a predictive biomarker of adverse cardiac events.
Highlights
Recent results obtained in our laboratory suggest that Growth and differentiation factor 15 (GDF15) could be an integrative biomarker for severe in-hospital heart failure (HF) in patients with acute myocardial infarction (AMI)
Levels of GDF15, which are associated both with angiotensin-converting enzyme 2 (ACE2) levels and a higher risk of mortality, might be used as a biomarker to better identify the risk of severe COVID-19 infection [164]
GDF15 is emerging as a relevant contributor to energy homeostasis and it appears to be a biomarker of various cardiovascular and metabolic diseases
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Cardiomyogenesis during mammalian heart development is initiated with the involvement of cardiogenic precursor cells derived from the embryonic mesoderm, which themselves are specified through a series of paracrine and autocrine gene regulatory signals. The presence of fibroblasts, ECs, SMC, neurons, and immune cells contributes to cardiomyocyte maturation. Cardiac fibroblasts are responsible for myocardial extracellular matrix homeostasis They are central actors in normal cardiac physiology and play an essential role in development by depositing collagen and ECM factors. Activation is associated with upregulation of activated fibroblast markers such as periostin, lysyl oxidase, and prolyl-4-hydroxylase These cells play an essential role in the fibrotic healing response. Ated by a range of chemical and physical stimuli [5,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
