No 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...