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Abstract-The molecular mechanisms by which extreme blood pressure elevation leads to vascular injury are not defined.To explore the hypothesis that activation of endothelium and platelets as manifested by increased concentrations of circulating endothelial microparticles and platelet microparticles could play a role in this target organ injury, we conducted a cross-sectional study of these markers in 3 groups: (1) untreated patients referred specifically for treatment of severe uncontrolled hypertension; (2) untreated patients with established mild hypertension; and (3) normotensive volunteer subjects. By ANOVA, endothelial (Pϭ0.002) and platelet (Pϭ0.01) microparticles were greatest in the severely hypertensive group. There was a significant correlation between both of these markers and blood pressure, even in the setting of multiple risk factors. Our results suggest that these markers may be useful and specific for pressure-induced endothelial and platelet activation in hypertension. Furthermore, because of the combined effects of endothelial and platelet microparticles on coagulation, leukocytes, and endothelium, it is possible that they may play a pathogenic role in mediating target organ injury in severe hypertension. Key Words: hypertension, arterial Ⅲ endothelium Ⅲ platelets Ⅲ endothelium-derived factors Ⅲ cell adhesion molecules S evere, uncontrolled hypertension is associated with high rates of target organ complications, 1-6 but the molecular mechanisms by which extreme blood pressure elevation leads to vascular injury are not well defined. Increasing evidence suggests that hypertension confers a prothrombic state, characterized by abnormalities of endothelial function and platelet activation. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] This dysfunction is conferred by isolated systolic hypertension as well as simultaneous systolic and diastolic hypertension. 9 Consequently, investigative interest has recently focused on endothelial and platelet activation as important mediators of hypertensive vascular injury.Endothelial microparticles (EMP) are small membrane vesicles that are shed from the surface of endothelial cells in response to activation, injury, and/or apoptosis. EMP release can be caused by a number of cytokines such as interleukin-1 and tumor necrosis factor and by elevated shear pressure. [25][26][27][28][29][30] Assays for circulating EMP have recently been developed 25-26 as potential means of quantifying endothelial cell injury. EMP are also known to be elevated in thrombotic thrombocytopenic purpura, 26 a condition associated with endothelial injury, and in acute coronary syndromes. 27,30 Increased EMP release has also been associated with endothelial injury in patients with multiple sclerosis and lupus anticoagulant. 25,28 -29 Circulating platelet microparticle (PMP) concentration is a marker of platelet activation. [31][32][33] PMP are formed by platelet membrane vesicle formation and shedding. 31 PMP are known to possess procoagulant activity and are elev...

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Endothelial microparticles (EMP) are small vesicles released from disturbed endothelial cells (EC). Owing to the central importance of EC injury in thrombotic and inflammatory conditions, assay of EMP as a marker of EC disturbance has come under intensive development by several laboratories. The review begins with established markers of EC injury, commonly soluble markers such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, von Willebrand factor (vWF), etc., pointing out that many of these are in fact mixtures of true soluble molecules with membrane-bound forms, for example, EMP. Assays of EMP from different labs are reviewed and standardization of assay is recommended. EMP are heterogeneous: those released in activation vs. apoptosis are distinctive in phenotypic markers and procoagulant properties. Application of EMP phenotype analysis can distinguish EC state of activation from apoptosis. Some EMP carry functional vWF with properties different from soluble vWF. Certain EMP bind to and activate monocytes; EMP-monocyte conjugates were found to be a marker of inflammatory disease such as multiple sclerosis (MS), and to enhance transendothelial migration of leukocytes in vitro. Clinical studies have revealed elevated plasma levels of EMP in lupus anticoagulant (LA), multiple sclerosis (MS), thrombotic thrombocytopenic purpura (TTP), coronary artery disease (CAD), hypertension, preeclampsia, and diabetes. Further refinement of EMP assay could open new windows for evaluating and monitoring endothelial injury in thrombotic and inflammatory disorders.

Endothelial dysfunction is evident during exacerbation of MS, evidenced by shedding of EMP expressing PECAM-1 (CD31). The in vitro data indicate contribution of one or more plasma factors in endothelial dysfunction of MS.

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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.