Abstract 115: Comparison Of Di-block Copolymer-based Cell Membrane Stabilizers To The Tri-block Poloxamer 188 In Protecting Coronary Artery Endothelial Cells Against Hypoxia-Reoxygenation Injury

Abstract

The triblock copolymer-based cell membrane stabilizer (CCMS) Poloxamer (P)188 consists of a central hydrophobic poly-propylene oxide (PPO) block that is flanked by two hydrophilic poly-ethylene oxide (PEO) blocks (PEO 75 -PPO 30 -PEO 75 ). It has been found to protect against various types of ischemia/reperfusion (IR) injury (e.g. stroke, traumatic brain injury, trauma, myocardial infarction) presumably by preserving membrane integrity and function. Modifications of its structure to di-block compounds (PEO-PPO) with a strongly hydrophobic (t) tert-butyl end-terminal were reported to yield even stronger protection. Recently, we demonstrated the critical importance of endothelial cells in mediating protection against IR injury of cardiomyocytes in a co-culture study. Here, we compared the protective effects of custom-made di-blocks (PEO 113 -PPO 10 t, PEO 226 -PPO 18 t and PEO 113 -PPO 20 t) at different concentrations (0 to 300 μM) on cell proliferation, lactate dehydrogenase (LDH) leakage and FM1-43 dye incorporation as markers of cell viability and membrane damage, respectively, to P188 in mouse coronary artery endothelial cells (MCAECs) when given upon the beginning of 2 hrs reoxygenation after 24 hrs hypoxia (HR) vs corresponding control normoxia (CN) conditions. Data are mean +/- standard deviation; statistics: ANOVA and SNK post-hoc testing, alpha = 0.05, # vs CN, * vs 0 mM. P188 as well as all three tested di-blocks significantly attenuated HR-induced cell damage dose-dependently; the figure shows the LDH data. This, for the first time, demonstrates that di-block compounds can protect MCAECs against HR injury as effective and even superior to P188. If translated clinically, di-block CCMS may become effective new compounds mitigating IR injury.