HIF‑1α mediates the protective effect of plasma extracellular particles induced by remote ischaemic preconditioning on oxidative stress injury in human umbilical vein endothelial cells

Abstract

Remote ischaemic preconditioning (RIPC) is considered to alleviate myocardial ischaemia/reperfusion (I/R) injury. The present study explored whether blood plasma particulate matter, which is termed extracellular particles (EPs), and is released from cells during RIPC, could reduce H 2 O 2 -induced damage in human umbilical vein endothelial cells (HUVECs). Firstly, EPs were derived from volunteers who did or did not undergo RIPC. To induce RIPC in volunteers, a blood pressure cuff was alternatively inflated for 5 min and deflated for the same duration for four successive cycles. HUVECs were assigned to two groups: i) Group 1 was preincubated for 24 h with EPs from volunteers after sham-RIPC, then treated with H 2 O 2 (1 mM; 6 h) to mimic the in vivo conditions of I/R-induced oxidative stress; and ii) group 2 was preincubated for 24 h with EPs from volunteers after RIPC, then treated with H 2 O 2 . Subsequently, EPs were derived from rats received sham-RIPC or RIPC and/or cadmium (Cd) pre-treatment. To induce RIPC in rats, a remote hind limb preconditioning stimulus was delivered using a blood pressure cuff attached at the inguinal level of the rat. The blood pressure cuff was alternatively inflated for 5 min and deflated for the same time period for four successive cycles. HUVECs were assigned to six groups: i) Group 1 was untreated; ii) group 2 received only H 2 O 2 treatment (1 mM; 6 h); iii) group 3 was preincubated for 24 h with EPs from rats exposed to sham-RIPC, then treated with H 2 O 2 ; iv) group 4 was preincubated for 24 h with EPs from rats that received an intraperitoneal injection of 1 mg/kg Cd [a pharmacological inhibitor of hypoxia-inducible factor 1-α (HIF-1α) in vivo ] 180 min before sham-RIPC, then treated with H 2 O 2 ; v) group 5 was preincubated for 24 h with EPs from rats exposed to RIPC, then treated with H 2 O 2 ; and vi) group 6 was preincubated for 24 h with EPs from rats that received an intraperitoneal injection of 1 mg/kg Cd 180 min before RIPC, then treated with H 2 O 2 . Cell viability and cytotoxicity were monitored using Cell Counting Kit-8 and lactate dehydrogenase assays. Cell apoptosis and necrosis were assessed via flow cytometry and western blot analysis. A notable increase in EP concentration in the plasma of volunteers after RIPC compared with that in the plasma of volunteers after sham-RIPC was observed. RIPC-associated EPs (RIPC-EPs) from volunteers could improve cell viability and reduce cytotoxicity, cell apoptosis and necrosis in HUVECs treated with H 2 O 2 in vitro . Furthermore, RIPC caused a signi...

Mitochondria and ischemia reperfusion injury

“…after chemotherapy or with steatosis, may unveil the boundaries of this technique, frequently applied during liver resection for tumour diseases. A few mechanistic studies unveil the underlying mechanism of action, which appears to be mediated through the upregulation of defences mechanisms, including hypoxia-inducible-factor-1-α (HIF-1alpha) [75].…”