GDF15 and heart failure: Under normal physiological conditions, GDF15 is rarely expressed in the heart, whereas in response to cardiovascular injuries, such as pressure overload, infarction,69 ischemia reperfusion, or heart failure, its expression is dramatically increased, being primarily derived from defective endothelial cells, hypoxic cardiomyocytes, activated macrophages and atherosclerotic plaques (Figure 2A).70