Circulating endothelial cells and endothelial activation in essential thrombocythemia: Results from CD146⁺ immunomagnetic enrichment—flow cytometry and soluble E‐selectin detection

Abstract

Circulating endothelial cells (CECs) have been studied in cardiovascular disorders and as a marker of angiogenetic activity; clinical applications are limited by a lack of consensus on their phenotypic identification and quantification. We determined CECs in essential thrombocythemia (ET) patients, to investigate their possible pathogenetic role. We considered CECs as CD146 1 /CD45 2 nucleated cells, detected in peripheral blood from 21 healthy controls and 39 ET patients, performing a combination of pre-enrichment of CD146 1 circulating cells and multiparametric flow cytometry measurement (FCM). Levels of CECs in ET patients were higher with respect to controls (median 2844 CECs/mL vs. 121.3 CECs/ mL, P < 0.0001). Apparently hydroxyurea treatment did not influence the levels of CECs. As another established marker of endothelial activation, we also assessed soluble E-selectin (sE-selectin) levels in 31 of the ET patients and compared with 39 healthy volunteers: median sE-selectin level in ET patients was 35.3 ng/mL, higher with respect to controls (24.48 ng/mL), P 5 0.0369. Our data suggest that endothelium in ET is activated, reflecting a significant role of angiogenesis in this disorder and suggesting an important endothelial contribution in the hypercoagulable state of ET patients.

Stalled cerebral capillary blood flow in mouse models of essential thrombocythemia and polycythemia vera revealed by in vivo two‐photon imaging

“…In support of this idea, the percentage of platelets with high levels of P‐selectin is increased in ET patients with a history of thrombosis compared with those without . ET patients are also more likely to have an increase in soluble E‐selectin, suggesting endothelial activation, and increased circulating microparticles, which amplify thrombogenesis . Furthermore, prothrombin fragments, thrombomodulin and von Willebrand factor have been found to be elevated in both PV and ET , suggesting a prothrombotic environment.…”

Effect of standard chemotherapy and antiangiogenic therapy on plasma markers and endothelial cells in colorectal cancer

“…The population variances (standard deviation/interquartile range) of these molecules are relatively large, and are not specific for cancer, and so we cannot exclude the possibility of a false negative owing to the small number of patients in each of the intervention groups. Despite this, soluble E selectin may be involved in angiogenesis ( Koch et al , 1995 ; Kumar et al , 2003 ; Belotti et al , 2012 ) and vasculogenesis ( Oh et al , 2007 ), although (in breast cancer) this has been disputed ( Hebber and Peyrat, 2000 ). In our hands, although soluble E selectin fell significantly in the entire cohort, this was due to a marked fall in those on surgery plus standard chemotherapy alone (the largest group of 32 patients): there was no significant change in those on surgery alone ( n =16) or those on surgery plus standard chemotherapy plus anti-VEGF therapy ( n =20).…”

Myeloproliferative neoplasms and thrombosis

“…27 High levels of circulating endothelial cells (resting, activated, apoptotic, and circulating precursor endothelial cells) are measured in MPN. [28][29][30] In addition, high circulating levels of endothelial activation markers, such as thrombomodulin, selectins, and von Willebrand factor, are released and favor the formation of cellular aggregates.…”