TY - JOUR
T1 - Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism
AU - Chirinos, Julio A.
AU - Heresi, Gustavo A.
AU - Velasquez, Hermes
AU - Jy, Wenche
AU - Jimenez, Joaquin J.
AU - Ahn, Eugene
AU - Horstman, Lawrence L.
AU - Soriano, Andres O.
AU - Zambrano, Juan P.
AU - Ahn, Yeon S.
N1 - Funding Information:
This work was supported by the Wallace H. Coulter Foundation and funds from Mary Beth Weiss, Jane and Charles Bosco, and gifts from Frank Smather.
Funding Information:
The presence of elevated EMP in this study reflects increased endothelial activation in VTE, consistent with prior studies ( 11,12 ). Under physiological conditions, the vascular endothelium plays a potent antithrombotic role, but upon endothelial activation is shifted toward a prothrombotic state ( 13 ); EC activation is associated with EMP release ( 2 ). Additionally, activated EC express tissue factor (TF), the main trigger of thrombin generation. Endothelial microparticles express many receptors of the parent EC and can support thrombin generation by way of the TF/factor VIIa pathway ( 14 ). Coagulation is supported by the presence of phosphatidylserine ( 15 ), which is translocated from the inner to the outer leaflet of the cell membrane during EMP formation ( 6 ). Hence, EMP provides a source of TF as well as a catalytic surface for assembly of the prothrombinase complex ( 16 ). Taken collectively, these considerations suggest that EMP are not only a marker of endothelial activation in VTE, but play an active role in the thrombotic process. They may also link thrombosis to inflammation insofar as EMP, like PMP, have been shown to function as vectors for many inflammatory mediators ( 17 ). Further research is needed to define whether the circulating concentrations of EMP in VTE are sufficient to facilitate thrombus formation and mediate inflammation.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/5/3
Y1 - 2005/5/3
N2 - OBJECTIVES: The purpose of this research was to determine the levels of platelet, leukocyte, and endothelial activation and markers of cellular interactions in patients with venous thromboembolism (VTE). BACKGROUND: The details of interactions between endothelium, platelets, and leukocytes in VTE are not well understood. METHODS: We studied 25 patients with VTE and compared 25 healthy controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP) identified by CD31+/CD42b- (EMP31) or E-selectin (EMP62E); 2) platelet microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as percentage of leukocytes positive for CD41. RESULTS: Patients with VTE had marked elevations of EMP 31 (2,193 vs. 383 counts/μl; p = 0.003), EMP62E (368 vs. 223 counts/μl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p = 0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01). Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p < 0.0001). CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.
AB - OBJECTIVES: The purpose of this research was to determine the levels of platelet, leukocyte, and endothelial activation and markers of cellular interactions in patients with venous thromboembolism (VTE). BACKGROUND: The details of interactions between endothelium, platelets, and leukocytes in VTE are not well understood. METHODS: We studied 25 patients with VTE and compared 25 healthy controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP) identified by CD31+/CD42b- (EMP31) or E-selectin (EMP62E); 2) platelet microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as percentage of leukocytes positive for CD41. RESULTS: Patients with VTE had marked elevations of EMP 31 (2,193 vs. 383 counts/μl; p = 0.003), EMP62E (368 vs. 223 counts/μl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p = 0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01). Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p < 0.0001). CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.
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U2 - 10.1016/j.jacc.2004.12.075
DO - 10.1016/j.jacc.2004.12.075
M3 - Article
C2 - 15862420
AN - SCOPUS:20944438125
VL - 45
SP - 1467
EP - 1471
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 9
ER -