Platelets and Platelet-Derived Extracellular Vesicles in Liver Physiology and Disease

Abstract

Beyond their role in hemostasis, platelets are proposed as key mediators of several physiological and pathophysiological processes of the liver, such as liver regeneration, toxic or viral acute liver injury, liver fibrosis, and carcinogenesis. The effects of platelets on the liver involve interactions with sinusoidal endothelial cells and the release of platelet-contained molecules following platelet activation. Platelets are the major source of circulating extracellular vesicles, which are suggested to play key roles in platelet interactions with endothelial cells in several clinical disorders. In the present review, we discuss the implications of platelet-derived extracellular vesicles in physiological and pathophysiological processes of the liver.

Figure 1

Roles of platelets and PEVs in ischemia‐reperfusion injury and acute liver injury. (A) After liver ischemia‐reperfusion injury and acute liver injury, such as hepatectomy, activated platelets in the sinusoid release several growth factors that can directly stimulate hepatocytes to proliferate or activate LSECs to further produce growth factors or factors, such as IL‐6, that regulate liver regeneration. (B) PEVs have opposite effects on the liver after injury. (B1) In ischemia/reperfusion, PEVs activate c‐jun N‐terminal kinase and nuclear factor‐kappa B in hepatocytes and contribute to cell injury. (B2) After acute liver injury and ischemia/reperfusion, PEVs can induce endothelium activation, which further promotes the recruitment, adhesion, and migration of monocytes and neutrophils and the secretion of cytokines, such as IL‐6. (B3) We propose that growth factor production by LSECs could modulate liver regeneration. Moreover, PEVs might have a direct effect on hepatocytes.