Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine.

Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine. Am J Physiol Endocrinol Metab. 2020 Jun 09;: Authors: Yuan HX, Chen CY, Li YQ, Ning DS, Li Y, Chen YT, Li SX, Fu MX, Li XD, Ma J, Jian YP, Liu DH, Mo ZW, Peng YM, Xu KQ, Ou ZJ, Ou JS Abstract We previously demonstrated that circulating extracellular vesicles(EVs) from patients with valvular heart disease(VHD, vEVs) contain inflammatory components and inhibit endothelium-dependent vasodilation. Neutrophil chemotaxis plays a key role in renal dysfunction, and dexmedetomidine (DEX) can reduce renal dysfunction in cardiac surgery. However, roles of vEVs in neutrophil chemotaxis, and effects of DEX on vEVs are unknown. Here, we investigated the impact of vEVs on neutrophil chemotaxis in kidneys and the influence of DEX on vEVs. Circulating EVs were isolated from healthy subjects and patients with VHD. Effects of EVs on chemokines generation, forkhead box protein O3a (FOXO3a) pathway activation and neutrophil chemotaxis on cultured human umbilical vein endothelial cells (HUVECs) and kidneys in mice, and the influence of DEX on EVs were detected. vEVs increased FOXO3a expression, decreased phosphorylation of Akt and FOXO3a, promoted FOXO3a nuclear translocation and activated the FOXO3a signaling pathway in vitro. DEX pretreatment reduced vEV-induced CXCL4 and CCL5 expression, and ne...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research