Statin decreases endothelial microparticle release from human coronary artery endothelial cells: implication for the Rho-kinase pathway

Objective. Elevated plasma levels of endothelial microparticles (EMPs) are associated with the presence of clinical atherosclerosis. Considering the anti-inflammatory properties of HMG-CoA reductase inhibitors on the endothelium, we studied the effect of fluvastatin on the release of EMPs in cultured human coronary artery endothelial cells (HCAEC). Methods and results. EMPs were generated in TNF-alpha-activated HCAECs. The absolute number of EMPs was enumerated using a novel two-color flow cytometric immunostaining technique with TruCount beads as an internal reference. EMPs are defined as EC membrane vesicles (1-2 mum in size) with a characteristic immunophenotype. The addition of fluvastatin to TNF-alpha-activated HCAECs significantly suppressed EMP release. Fluvastatin suppressed TNF-alpha-induced Rho activation. The Rho-kinase inhibitor, Y-27632, reproduced the effect of statin. Conclusion. EMP release from TNF-alpha-activated HCAECs is suppressed by fluvastatin. In addition,the Rho/Rho-kinase may play an important role in modulating EMP release. (C) 2004 Elsevier Inc. All rights reserved.