Abstract 22: Endothelial Nitric Oxide Synthase Activation by Nano-Polymer Polyethylene-Oxide is Dependent on Nanomolecule Size and Concentration
Background: Nanopolymers can integrate into the systemic circulation and modify characteristics of blood flow. Polyethylene oxide (PEO) nanopolymer reportedly affects vascular endothelium through modification of near wall shear stress. This leads to phosphorylation of Endothelial Nitric Oxide Synthase eNOS (S1177), eNOS dependent NO increase and cardioprotection from focal ischemia reperfusion injury.
Aim: We investigated whether or not eNOS upregulation and phosphorylation produced by PEO nanopolymers is depedent on its molecular size and concentration.
Methods: Human endothelial cells were cultured inside the silicon tubing (L200 mm ID5 mm) and perfused 2 hrs with PEO 1000, 2000, 5000 and 10000 kDa 50 ppm solution (vehicle in controls (CONT)) in DMEM with pulsatile flow of 300 mL/min and pulse rate of 80 bpm. Another group was perfused with 5000 kDa PEO solution at 10, 20, 50 and 100 ppm. Levels of eNOS, p-eNOS (S1177) and flow parameters were measured.
Results: In cultures exposed to PEO nanopolymer under pulsatile flow we observed 1) Dose dependent increase of p-eNOS; 2) When applied at the same concentration nanopolymer of larger size produced higher increased in eNOS activation through phosphorylation; 3) p-eNOS changes in PEO experiments were significantly different from CONT.
Conclusions: Nanopolymers produce additional shear stress on the vascular endothelium which stimulates upregulation and phosphorylation of eNOS which is proportional to size and concentration of PEO.These findings are important for optimisizing the clinical effects of stimulating the endothelium through nanopolymers, to improve outcomes from ischemia reperfusion injury.
- © 2010 by American Heart Association, Inc.