Shuzhen Guo1, Monique Stins, MingMing Ning, Eng H Lo. 1. Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA. sguo@partners.org
Abstract
BACKGROUND: Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the brain. In this experimental cellular study, we asked whether dipyridamole can ameliorate brain endothelial injury after exposure to inflammatory and metabolic insults. METHODS: Human brain endothelial cells were grown in culture, and exposed to TNFalpha (continuously for 20 h) or subjected to oxygen-glucose deprivation (OGD; 6 h of insult followed by 18 h recovery). Expression of ICAM-1, VCAM-1 and PECAM-1 were measured by immunoblotting. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the conditioned media were quantified via zymography. MTT mitochondrial activity was measured to assess endothelial cell viability. RESULTS: Exposure of human brain endothelial cells to TNFalpha (12.5-50 ng/ml) induced a clear increase in protein levels of ICAM-1, VCAM-1 and MMP-9. TNFalpha did not alter PECAM-1. Dipyridamole (1-5 muM) significantly attenuated ICAM-1 and MMP-9 levels after this inflammatory insult. No significant effects of dipyridamole were noted for VCAM-1. Six-hour OGD induced moderate endothelial cell death accompanied by a release of MMP-9. Dipyridamole significantly decreased MMP-9 levels and cell death after this metabolic insult. CONCLUSIONS: These results suggest that dipyridamole may ameliorate brain endothelial injury after inflammation and/or metabolic insults. How these putative cellular mechanisms may relate to clinical outcomes and conditions in stroke patients remains to be elucidated. Copyright 2010 S. Karger AG, Basel.
BACKGROUND: Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the brain. In this experimental cellular study, we asked whether dipyridamole can ameliorate brain endothelial injury after exposure to inflammatory and metabolic insults. METHODS:Human brain endothelial cells were grown in culture, and exposed to TNFalpha (continuously for 20 h) or subjected to oxygen-glucose deprivation (OGD; 6 h of insult followed by 18 h recovery). Expression of ICAM-1, VCAM-1 and PECAM-1 were measured by immunoblotting. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the conditioned media were quantified via zymography. MTT mitochondrial activity was measured to assess endothelial cell viability. RESULTS: Exposure of human brain endothelial cells to TNFalpha (12.5-50 ng/ml) induced a clear increase in protein levels of ICAM-1, VCAM-1 and MMP-9. TNFalpha did not alter PECAM-1. Dipyridamole (1-5 muM) significantly attenuated ICAM-1 and MMP-9 levels after this inflammatory insult. No significant effects of dipyridamole were noted for VCAM-1. Six-hour OGD induced moderate endothelial cell death accompanied by a release of MMP-9. Dipyridamole significantly decreased MMP-9 levels and cell death after this metabolic insult. CONCLUSIONS: These results suggest that dipyridamole may ameliorate brain endothelial injury after inflammation and/or metabolic insults. How these putative cellular mechanisms may relate to clinical outcomes and conditions in strokepatients remains to be elucidated. Copyright 2010 S. Karger AG, Basel.
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