Diabetic plasma exosomes induce vascular endothelial dysfunction by upregulating the ERK1/2 signaling pathway

AIM To explore the effects of plasma exosomes derived from diabetic mice on vascular endothelial cell dysfunction and the underlying mechanisms.

METHODS An animal model of diabetes mellitus (DM) was established by combining high-fat diet feeding with low-dose streptozotocin intraperitoneal injection. After successful modeling, exosomes were isolated from the control group (control-exo) and the DM group (DM-exo). These exosomes were then administered to 8-week-old male C57BL/6J mice via tail vein injection to assess cardiac function and cardiac vascular density. For in vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with control-exo and DM-exo, respectively, to determine the expression and cellular localization of extracellular signal-regulated kinase (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2), the levels of inflammatory factors, as well as the migration and tube formation capabilities of HUVECs.

RESULTS The DM-exo group exhibited a decrease in cardiac vascular density and impaired cardiac diastolic function compared to the control-exo group (P<0.01). Moreover, HUVECs treated with DM-exo displayed reduced migration and tube formation abilities, an increased level of p-ERK1/2 to ERK1/2 ratio, and enhanced nuclear localization of ERK1/2 (all P<0.01). The ERK1/2 inhibitor SCH772984 could reverse the decrement of migration and tube formation abilities in HUVECs induced by DM-exo (P<0.01).

CONCLUSION Plasma exosomes from diabetic mice contribute to vascular endothelial dysfunction by facilitating the phosphorylation of ERK1/2 and its nuclear translocation.