Regulation of differentiation and reproduction of vascular organs by Edg receptor expression

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Objective: Palmitoyl-L-carnitine (palcar), which accumulates in ischemic heart, affects cellular functions of vascular endothelium in the ischemic area. The aim of the study was to examine the effects of palcar on intracellular Cat^<2+> concentration ([Ca^<2+>]i) in vascular endothelial cells in comparison with those of sphingosine-1-phosphate (S1P) and to investigate the underlying mechanisms. Methods and Results: Human umbilical vein endothelial cells (huvecs) were loaded with Fura-2 AM and the fluorescence signal was measured with Argus 50/CA imaging system. Application of palcar at a concentration range between 0.3 and 3μM elevated [Ca^<2+>]i i in huvecs and its potency was about 30 times lower than that of S1P. Although the sensitivity to palcar and S1P varied widely among huvecs from individuals, response to 3 μM palcar in each huvec clearly paralleled that to 0.3 μM S1P (r=0.79, P<0.001). In addition, huvecs that were treated with 100 ng/ml pertussis toxin (PTX) for 15 hr failed to respond to palcar as well as to S1P, but did respond to 3 μM His. On the other hand, pre-treatment of huvecs with palcar abolished subsequent S1P-induced elevation of [Ca^<2+>]i, but not the His-induced elevation. Conclusions: Our data indicate that palcar has a novel action on huvecs as a potential agonist of receptors for S1P. Effective inhibition of response to S1P by palcar suggests that palcar affects angiogenesis regulated by S1P.