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http://dx.doi.org/10.5352/JLS.2016.26.12.1367

Cilostazol Promotes the Migration of Brain Microvascular Endothelial Cells  

Lee, Sae-Won (Korean Medical Science Research Center for Healthy-Aging, Pusan National University)
Park, Jung Hwa (Korean Medical Science Research Center for Healthy-Aging, Pusan National University)
Shin, Hwa Kyoung (Korean Medical Science Research Center for Healthy-Aging, Pusan National University)
Publication Information
Journal of Life Science / v.26, no.12, 2016 , pp. 1367-1375 More about this Journal
Abstract
Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.
Keywords
Brain microvascular endothelial cell; expression microarray; ischemic disease; motility; therapeutic angiogenesis;
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