Grant: Operating Grant

Although the kidney, and to a lesser extent the liver, can increase serum EPO levels in response to hypoxia, it is unclear if they are the sole or primary contributor of serum EPO levels. Recently, EPO production has been reported in several non-renal tissues of mammals (e.g., brain, skeletal muscle, hair follicles, and uterus). While EPO's role was thought to be related strictly to erythropoiesis, it was the discovery of the presence of the EPO receptor in other tissues (e.g., heart, limb muscle and brain) that raised the possibility of EPO signaling unrelated to erythropoiesis, i.e., extrahaematopoietic effects. Exogenous EPO administration has been reported to reduce infarct size and prevent remodeling after acute myocardial infarction. We have recent preliminary evidence establishing that the heart produces EPO even during normoxia which increases with hypoxia. Furthermore, we have establish that induction of cardiac EPO helps to markedly reduce left ventricular hypertrophy and preserves cardiac function in response to chronic hypertension, suggesting that endogenous EPO plays an important role in enabling the heart to adapt to chronically working at high workloads without leading to the development of heart failure.