The clinical impact of growth differentiation factor-15 in heart disease: A 2019 update

Crit Rev Clin Lab Sci. 2020 Mar;57(2):114-125. doi: 10.1080/10408363.2019.1678565. Epub 2019 Oct 30.


Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1) or non-steroidal anti-inflammatory drug-activated gene (NAG-1) has been identified as a biomarker of response to treatment and prognosis in cardiovascular diseases. GDF-15 is a member of the transforming growth factor-β superfamily and is involved in several pathological conditions such as inflammation, cancer, cardiovascular, pulmonary and renal diseases. Cardiac myocytes produce and secrete GDF-15 in response to oxidative stress, stimulation with angiotensin II or proinflammatory cytokines, ischemia, and mechanical stretch. Other cellular sources of GDF-15 production are macrophages, vascular smooth muscle cells, endothelial cells, and adipocytes, which secrete GDF-15 in response to oxidative or metabolic stress or stimulation of proinflammatory cytokines. GDF-15 is induced in hypertrophic and dilated cardiomyopathy after volume overload, ischemia, and heart failure. GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).

Keywords: GDF-15; biomarkers; heart; stroke.

Publication types

  • Review

MeSH terms

  • Biomarkers
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cytokines / immunology
  • Growth Differentiation Factor 15 / metabolism*
  • Growth Differentiation Factor 15 / physiology*
  • Heart Diseases / metabolism*
  • Heart Diseases / physiopathology
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Humans
  • Inflammation / immunology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / physiology
  • Oxidative Stress / physiology
  • Predictive Value of Tests
  • Prognosis
  • Risk Factors


  • Biomarkers
  • Cytokines
  • GDF15 protein, human
  • Growth Differentiation Factor 15