Effects of Severe Hypertension on Endothelial and Platelet Microparticles

Abstract

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...

Elevated circulating endothelial microparticles and brachial–ankle pulse wave velocity in well-controlled hypertensive patients

“…1,6,9,19 In our study, hypertensive patients displayed both elevated levels of circulating EMPs and faster baPWV, which was consistent with the earlier studies. 19,20 Therefore, it is believed that antihypertensive treatment for patients with hypertension should restore the vascular dysfunction. In our study, WCHT patients did show reduced levels of circulating EMPs and slower baPWV to some extent, indicating that pressure-lowering therapy is critical in improving vascular function.…”

“…One is because of high BP as shown by the present data and earlier report. 20 The other one may be related to inflammatory stimulation on vascular endothelium. Similar to the earlier investigations, 31,32 this study showed that the patients with hypertension had increased CRP, which is a marker for the presence of inflammation.…”

“…18 It has been reported that in patients with hypertension, increased EMPs and reduced artery elasticity are present. 19,20 However, there are no data to show both circulating EMPs and baPWV levels in patients with controlled BP. In this study, we conducted a cross-sectional study to investigate the alteration of circulating CD31 þ /CD42À MPs and its relation to baPWV in well-controlled hypertensive (WCHT) patients and uncontrolled hypertensive (UCHT) patients compared with age-and gender-matched healthy subjects.…”

Vβ‐restricted T cell adherence to endothelial cells: A mechanism for superantigen‐dependent vascular injury

“…The morphologic characteristics of EMPs by electron microscopy have been well described by Combes et al (11). It is now becoming apparent that EMPs provide a window to the activated endothelium in a number of disease states in which endothelial injury is central to the disease process, including atherosclerosis (16), acute coronary syndromes (17), antiphospholipid syndrome (APS) (11), thrombotic thrombocytopenic purpura (TTP) (18), multiple sclerosis (MS) (19), and most recently, hypertension (20) in adults. Moreover, plasma from patients with APS, MS, or TTP was shown to induce the formation of EMPs from endothelial cells in tissue culture (11,18,19).…”

Endothelial microparticles correlate with erectile dysfunction in diabetic men

“…[8][9][10] Elevated numbers of circulating microparticles have been found in patients with a great variety of diseases with vascular involvement and hypercoagulability. [11][12][13][14][15] To the best of our knowledge, there are no reported studies that evaluated circulating microparticles in impotent diabetic men. Therefore, the aims of this study were (a) to evaluate circulating endothelial (EMP) and platelet microparticles (PMP) in diabetic men with ED, (b) to address the relation between circulating microparticles and the severity of ED and (c) to assess the relation between circulating microparticles and endothelial dysfunction.…”