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Intimal hyperplasia (IH) is a clinical concern leading to failure of up to 50% of vein grafts and 10% of arterial grafts after 10 years with no known current treatment. Recent studies have shown that hypoxia differentially regulates proliferation of vein derived smooth muscle cells (V-SMC) compared to artery derived smooth muscle cells (A-SMC). The objective of this study is to evaluate the effect of hypoxia on cellular migration and the mechanisms underlying the differential effects of hypoxia on A-SMC and V-SMC migration. Hypoxic treatment (3-5% O2) of Smooth Muscle Cells (SMC) resulted in differential migration in scratch wound and electric cell substrate impedance sensing (ECIS) assays. Hypoxia led to greater migration compared to normoxia with venous derived wound closure (V-SMC 30.8% Normoxia to 67% Hypoxia) greater than arterial wound closure (A-SMC 6.2% Normoxia to 24.7% Hypoxia). Paracrine factors secreted by hypoxic endothelial cells induced more migration in SMC compared to factors secreted by normoxic endothelial cells. Migration of V-SMC was greater than A-SMC in the presence of paracrine factors. Neutralizing antibody to Vascular Endothelial Growth Factor Receptor -1 (VEGFR-1) completely inhibited V-SMC migration while there was only partial inhibition of A-SMC migration. A-SMC migration was completely inhibited by Platelet Derived Growth Factor BB (PDGF-BB) neutralizing antibody. p38 Mitogen Activated Protein kinase (p38 MAPK) inhibitor pre-incubation completely inhibited migration induced by paracrine factors in both A-SMC and V-SMC. Our study determines that SMC migration under hypoxia occurs via both an autocrine and paracrine mechanism and is dependent on Vascular Endothelial Growth Factor-A (VEGF-A) in V-SMC and PDGF-BB in A-SMC. Migration of both A-SMC and V-SMC is inhibited by p38 MAPK inhibitor. These studies suggest that pharmacotherapeutic strategies directed at modulating p38 MAPK activity can be exploited to prevent IH in vascular grafts.

The oxidation of cysteamine by iodate and aqueous iodine has been studied in neutral to mildly acidic conditions. The reaction is relatively slow and is heavily dependent on acid concentration. The reaction dynamics are complex and display clock behavior, transient iodine production, and even oligooscillatory production of iodine, depending upon initial conditions. The oxidation product was the cysteamine dimer (cystamine), with no further oxidation observed past this product. The stoichiometry of the reaction was deduced to be IO 3 – + 6H 2 NCH 2 CH 2 SH → I – + 3H 2 NCH 2 CH 2 S-SCH 2 CH 2 NH 2 + 3H 2 O in excess cysteamine conditions, whereas in excess iodate the stoichiometry of the reaction is 2IO 3 – + 10H 2 NCH 2 CH 2 SH → I 2 + 5H 2 NCH 2 CH 2 S-SCH 2 CH 2 NH 2 + 6H 2 O. The stoichiometry of the oxidation of cysteamine by aqueous iodine was deduced to be I 2 + 2H 2 NCH 2 CH 2 SH → 2I – + H 2 NCH 2 CH 2 S-SCH 2 CH 2 NH 2 + 2H + . The bimolecular rate constant for the oxidation of cysteamine by iodine was experimentally evaluated as 2.7 (mol L –1 ) –1 s –1 . The whole reaction scheme was satisfactorily modeled by a network of 14 elementary reactions.Key words: cysteamine, cystamine, Dushman reaction, oligooscillations.