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Effect of ZNimesulide on the Differentiation and Survival of Endothelial Progenitor Cells  

Oh, Ho-Kyun (Cancer Research Institute, Catholic Research of Medical Science, The Catholic University of Korea)
Kim, Sun-Yong (Cancer Research Institute, Catholic Research of Medical Science, The Catholic University of Korea)
Baek, Sang-Hong (Department of Internal Medicine, Division of Cardiovascular Medicine, The Catholic University of Korea)
Lim, Sung-Cil (Department of Internal Medicine, Division of Cardiovascular Medicine, The Catholic University of Korea)
Ahn, Hyun-Young (Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Korea Institute of Radiological and Medical Sciences)
Shin, Jong-Chul (Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Korea Institute of Radiological and Medical Sciences)
Hong, Sung-Hee (Laboratory of Experimental Therapeutics, Korea Institute of Radiological and Medical Sciences)
Hong, Yong-Kil (Cancer Research Institute, Catholic Research of Medical Science, The Catholic University of Korea)
Joe, Young-Ae (Cancer Research Institute, Catholic Research of Medical Science, The Catholic University of Korea)
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Biomolecules & Therapeutics / v.12, no.4, 2004 , pp. 221-227 More about this Journal
Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors have been shown to decrease the growth of tumor, in part, by inhibition of neovascularization. Recently, besides mature endothelial cells, endothelial progenitor cells (EPCs) have been shown to contribute neovascularization in angiogenic tissues. In this study, we addressed a question whether nimesulide, a selective COX-2 inhibitor, could affect differentiation of EPCs into adhesive endothelial cells in vitro. Total mononuclear cells were isolated from cord blood by Ficoll density gradient centrifugation, and then the cells were incubated with nimesulide or vehicle control for 7 days. The number of adherent and spindle-shaped cells decreased by nimesulide treatment in a concentration-dependent fashion at a concentration range of 5 - 200 ${\mu}M$. Moreover, the adherent cells double positive for DiI-ac-LDL uptake and lectin binding significantly decreased upon nimesulide treatment. There was no change of expression of CD31 between treatment and control groups, whereas slight reduction was detected upon treatment in expression of VE-cadherin, ICAM-1, vWF, ${\alpha}v$, and ${\alpha}5$. Nimesulide also reduced cell viability during first 3 days' culture and induced apoptosis in adherent EPCs, resulting in increased annexin-V-positive and propidium iodide-negative cells. Taken together, these results suggest that nimesulide could be applied for the inhibition of new vessel formation, in part, by inhibiting differentiation and survival of EPCs.
nimesulide; endothelial progenitor cells; nonsteroidal anti-inflammatory drugs (NSAIDs); differentiation; apoptosis;
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