Erythrocytes as a Source of Exerkines

Exercise activates many metabolic and signaling pathways in skeletal muscle and other tissues and cells, causing numerous systemic beneficial metabolic effects. Traditionally recognized for their principal role in oxygen (O₂) transport, erythrocytes have emerged as dynamic regulators of vascular homeostasis. Beyond their respiratory function, erythrocytes modulate vascular tone through crosstalk with other cells and tissues, particularly under hypoxia and physical exercise. This regulatory capacity is primarily mediated through the controlled release in the bloodstream of adenosine triphosphate (ATP) and nitric oxide (NO), two potent vasodilators that contribute significantly to matching oxygen supply with tissue metabolic demand. Emerging evidence suggests that many other erythrocyte-released molecules may act as additional factors involved in tissue-erythrocyte crosstalk. This review highlights erythrocytes as active contributors to exercise-induced adaptations through their exocrine signaling.