title: Statin decreases endothelial microparticle release from human coronary artery endothelial cells: implication for the Rho-kinase pathway.
abstract: 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).
  
  
  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 microm 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Department of Pathology, The New York Harbor VA Health Care System, Manhattan Campus, 423 East 23rd Street, New York, NY 10010, USA. antoniotramontano@hotmail.com
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Tramontano
authors.forename: Jeanne
authors.initials: J
authors.lastname: O'Leary
authors.forename: Aislinn D
authors.initials: AD
authors.lastname: Black
authors.forename: Ranganath
authors.initials: R
authors.lastname: Muniyappa
authors.forename: Michael V
authors.initials: MV
authors.lastname: Cutaia
authors.forename: Nabil
authors.initials: N
authors.lastname: El-Sherif
mesh_terms: D015703:Antigens, CD; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D039564:Integrin alphaV / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000097:blood* / Q000187:drug effects* / Q000276:immunology; D010316:Particle Size; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D054460:rho-Associated Kinases
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D039564:Integrin alphaV; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000077340:Fluvastatin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases