Polyethylene-Oxide (PEO) Linear Nano-Polymer Directly Stimulates Endothelium and Protects Myocardium from Focal Ischemia-Reperfusion Injury via eNOS Pathway in Rats

摘要

Medical grade Nano-polymers (NP) used to enhance circulation, drug and gene delivery. Injection of Polyethylene-oxide (PEO) increase tissue perfusion and decrease mean blood pressure in animal models. Polyethylene-oxide (PEO) NP's ultra high molecular weight (2-5 × 10^6 Da) and rheological properties allow it to interact with endothelial cells to increase endothelial nitric oxide (eNO) and its attendant enzyme (eNOS). eNOS over-expression and eNO induction is known to provide cardioprotection. We hypothesized that injection of PEO will have cardioprotective properties in a model of myocardial ischemia reperfusion injury (I/R), via induction of eNOS due to direct stimulation of endothelium. Male rats (310±9 g, n=16) were randomized to IV injection of 10 ppm of a saline-PEO solution (PEO) or equal volume of saline (CONT). Focal I/R injury was induced by LAD ligation for 30 minutes followed by 60 min of reperfusion. ECG, and aortic pressure monitored continuously and infarct size calculated as % area at risk. eNOS and its active phosphorylated form (p-eNOS) were detected on Western blots in left ventricle protein extracts. Mean blood pressure was 78±10 and 75±6 in PEO compared to 58±12 and 66±4 in CONT, at 30 min of Ischemia and 60 min reperfusion respectively (p<0.05 PEO vs. CONT). PEO had 28% and 47% higher eNOS and p-eNOS vs. CONT. PEO had a 28% infarct sparing effect compared to CONT. PEO prior to myocardial infarction significantly reduces infarct size and induces activation and up regulation of eNOS pathway. This is a possible novel mechanism for PEO NP cardioprotective effect and behavior in blood circulation. These properties of PEO warrant further investigation.