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Endothelium-derived microparticles inhibit human cardiac valve endothelial cell function. Shock 2006 Jun;25(6):575-80



Pubmed ID




Scopus ID

2-s2.0-33745602812   43 Citations


Elevated numbers of endothelium-derived microparticles (EMPs) in the circulation are found in a variety of critical illnesses. EMPs have been associated with vascular dysfunction, including thrombotic complications and loss of normal vascular reactivity, common responses associated with cardiac valve injury. However, the exact mechanisms of this dysfunction and the potential impact on cardiac endothelium are unknown. We hypothesize that pathologic levels of circulating EMPs negatively regulate proliferation and migration of valvular endothelial cells (ECs), leading to downstream endothelial dysfunction. EMPs were generated from plasminogen activation inhibitor 1-stimulated human umbilical vein endothelial cells (HUVECs). Human mitral valve endothelial cells (HMVECs) were isolated and characterized by platelet endothelial cell-derived adhesion molecule-1 (PECAM-1, or CD31) and von Willebrand factor immunocytochemistry. HMVECs were treated with increasing EMP doses, and then, the effects of EMPs on growth factor-induced proliferation and migration were tested. Proliferation was assessed by H-thymidine incorporation. EC migration was assayed by photographing microtubules of HMVECs and HUVECs in fibrin gel incubated with EMPs +/- growth factors for 48 h. The EMP effects on non-valve HUVECs were tested in parallel. EMPs inhibited HMVEC proliferation at high doses but stimulated HUVEC proliferation at all doses. In HMVECs, EMPs inhibited basic fibroblast growth factor- and vascular endothelial growth factor-induced proliferation and migration. Taken together, these data suggest EMPs regulate valvular EC proliferation in a dose-dependent manner and, furthermore, modulate growth factor signaling in ECs. These results implicate EMPs as a possible source of downstream EC dysfunction in disease states. EMPs may play a role in valvular leaflet injury in human disease by inhibiting normal growth and repair of endothelium.

Author List

Klinkner DB, Densmore JC, Kaul S, Noll L, Lim HJ, Weihrauch D, Pritchard KA Jr, Oldham KT, Sander TL


John C. Densmore MD Professor in the Surgery department at Medical College of Wisconsin
Keith T. Oldham MD Professor in the Surgery department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Dorothee Weihrauch DVM, PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Movement
Cell Proliferation
Cells, Cultured
Endothelial Cells
Endothelium, Vascular
Heart Valve Diseases
Mitral Valve
Plasminogen Activator Inhibitor 1
Platelet Endothelial Cell Adhesion Molecule-1
Serine Proteinase Inhibitors
Umbilical Veins
von Willebrand Factor
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a