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Wenche Jy

Publications and source records attributed to Wenche Jy.

31 records · Page 2Linked to original sources
PubMed2004

Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension.

OBJECTIVE: Elevated plasma endothelial microparticle levels have been found to be elevated in women with preeclampsia. However, their role in distinguishing preeclampsia from gestational hypertension remains to be elucidated. The objectives of this study were to compare endothelial microparticle levels among patients with preeclampsia, gestational hypertension, and healthy pregnant control subjects and to evaluate the effect of plasma from women with preeclampsia and gestational hypertension on the release of endothelial microparticles by renal microvascular endothelial cells. STUDY DESIGN: A prospective study was conducted on 52 women with preeclampsia, 20 women with gestational hypertension, and 38 healthy pregnant control subjects. Endothelial microparticles were measured by flow cytometry with fluorescent monoclonal mouse anti-human antibodies against CD31, CD42b, and CD62E. RESULTS: CD31 + /42b - endothelial microparticle levels were 10497 +/- 5145 counts/microL in women with preeclampsia versus 6768 +/- 1810 counts/microL in women with gestational hypertension ( P < .01). In control subjects, CD31 + /42b - endothelial microparticle levels were 6119 +/- 3592 counts/microL. CD62E + endothelial microparticle levels were 1930 +/- 966 counts/microL in women with preeclampsia versus 822 +/- 150 counts/microL in women with gestational hypertension ( P <.01). In control subjects, CD62E + endothelial microparticle levels were 712 +/- 160 counts/microL. Incubation of renal microvascular endothelial cells with plasma from women with preeclampsia resulted in a rise in CD31 + and CD62E + endothelial microparticle levels as compared with women with gestational hypertension and control subjects. CONCLUSION: Endothelial microparticle levels are higher in women with preeclampsia than in women with gestational hypertension and control subjects. The measurement of endothelial microparticles may be useful as a diagnostic tool for preeclampsia in pregnant women.

Adult↗
PubMed2004

Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes.

BACKGROUND: Endothelial Microparticles (EMP) are small fragments of endothelial cell membrane shed during apoptosis or activation. Our group has previously reported elevations of EMP in patients with coronary artery disease (CAD), thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis (MS), and severe hypertension (HTN). In the present study, we evaluate the possible relationship between EMP levels and the angiographic severity and characteristics of coronary obstructive lesions. METHODS: We studied a total of 43 patients undergoing coronary angiography. Fifteen had presented with acute myocardial infarction (MI), 20 with unstable anginas (UA), 5 with stable angina (SA) and 3 with congestive heart failure. Coronary angiography was reviewed and coronary lesions were classified using the Ambrose classification. Coronary stenoses were classified as high and low risk. High-risk included lesions with eccentric appearance (type II), presence of thrombi, or multiple irregularities. Low-risk lesions were defined as concentric or type I. Lesions were also analyzed by degree of stenosis and history of acute coronary syndrome (ACS). EMP in plasma was assayed by flow cytometry. RESULTS: EMP in eccentric type II or multiple irregular lesions (high-risk) were 2.5-fold higher than in type I or concentric (low-risk) lesions, p<0.05. Lesions with thrombi had three-fold higher EMP than those without (p=0.05). Mild stenosis (>20%-<45%) had three-fold higher EMP than more severe (>45%), and five-fold higher than those without stenosis (p<0.01). Among patients with type II lesions, those with first ACS episode had four-fold higher EMP levels than those with recurrent ACS (p<0.01). CONCLUSION: High EMP was associated with high-risk angiographic lesions including eccentric type II, multiple irregular, and lesions with thrombi. Mild to moderate stenosis was associated with higher EMP levels than severe stenosis. EMP may be a useful marker in detecting endothelial injury and risk of ACS as defined by angiography.

Acute Disease↗
PubMed2004

Differences of soluble CD40L in sera and plasma: implications on CD40L assay as a marker of thrombotic risk.

INTRODUCTION: Soluble CD40L (sCD40L) ELISA has emerged as a promising predictor of poor outcomes in acute coronary syndrome. Yet many blood processing techniques have been used with little consideration of their effect on the results. METHODS: We measured sCD40L by ELISA in 10 patients with thrombocytopenia and 12 with normal or high platelet counts and 8 healthy controls using three sampling techniques: serum clotted on ice (serum-I) or at room temperature (serum-RT) and platelet poor plasma (PPP). RESULTS: Serum-RT samples, compared to serum-I, gave significantly higher CD40L values (p=0.003), demonstrating that ex vivo sCD40L release by activated platelets is inhibited by cold temperature. Although serum-I and PPP were comparable in patients with normal platelet counts, serum-I gave significantly higher values than PPP in the thrombocytosis group (p=0.01), suggesting that cold inhibition is insufficient in the latter group. To estimate the fraction of sCD40L that was microparticle-bound CD40L (mp-CD40L), 16 samples underwent 0.1-microm filtration. 50.6% of sCD40L was mp-CD40L in serum-RT, whereas 21.3% and 29.9% were observed in serum-I and PPP, respectively. Lastly, plasma sCD40L was assayed in 46 patients with and 35 without thrombosis. Plasma sCD40L did not correlate with platelet count in non-thrombotic, non-inflammatory patients but did (p<0.01) in those with thrombosis. CONCLUSIONS: Sample processing and temperature profoundly affect sCD40L assay. Serum-I and PPP minimize the release of sCD40L ex vivo and better represent sCD40L in vivo. However, PPP may be preferable particularly in patients with thrombocytosis. The existence of mp-CD40L highlights the importance of centrifuge conditions.

Adult↗
PubMed2004

New horizons in the analysis of circulating cell-derived microparticles.

Analysis of circulating cell-derived microparticles (MP) is becoming more refined and clinically useful. This review, stemming from lectures given at Tokyo late 2003, does not repeat prior reviews but focuses on new horizons. A major theme is the rising recognition of platelets and their MP (PMP) as key mediators of inflammation/immunity. Among the major concepts developed are that (i) many so-called soluble markers of inflammation are in reality MP-bound; (ii) PMP and other MP appear to serve important signaling and immune functions including antigen presentation. In conclusion, MP analysis is poised to enter the mainstream of clinical testing, measuring specific antigens rather than gross levels. However, more research is needed to decisively establish their functions, and international standards are needed to allow comparing results from different laboratories.

Biomarkers↗
PubMed2003

Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis.

BACKGROUND: Endothelial cells (EC) shed endothelial microparticles (EMP) in activation and apoptosis. OBJECTIVES: We compared the antigenic expression of EMP species released during activation as compared to apoptosis, in three cell lines. METHODS: EC from renal and brain microvascular (MiVEC) and coronary macrovascular (MaVEC) origin were incubated with TNF-alpha to induce activation, or deprived of growth factors to induce apoptosis. Antigens expressed on EMP and EC were assayed flow cytometrically and included constitutive markers (CD31, CD51/61, CD105), inducible markers (CD54, CD62E and CD106), and annexin V binding. RESULTS: It was found that in apoptosis, constitutive markers in EMP were markedly increased (CD31>CD105), with a concomitant decrease in expression in EC. Annexin V EC surface binding and annexin V+ EMP were more sharply increased in apoptosis than in activation. In contrast, in activation, inducible markers in EMP were markedly increased in both EMP and EC (CD62E>CD54>CD106). Coronary MaVEC released significantly less EMP than MiVEC. CONCLUSION: EC release qualitatively and quantitatively distinct EMP during activation compared to apoptosis. Analysis of EMP phenotypic signatures may provide clinically useful information on the status of the endothelium.

Antigens, CD↗
PubMed2003

High levels of circulating endothelial microparticles in patients with acute coronary syndromes.

BACKGROUND: Endothelial injury plays a critical role in coronary artery disease (CAD), but the assessment of this injury has been problematical. Recently, it has been shown in vitro that endothelial cells (ECs) release endothelial microparticles (EMPs) on activation or apoptosis and that an assay of EMPs can provide useful information on EC status in patients with thrombotic disorders. This study is aimed at assessing possible correlations between EMPs, which are markers of endothelial injury, and clinical subgroups of patients with CAD. METHODS: A prospective, case-controlled study was conducted on 84 patients with CAD and 42 control subjects to investigate EMP profiles. Included were 64 patients with acute coronary syndromes ([ACS], 38 with myocardial infarction [MI] and 26 with unstable angina [UA]) and 20 patients with stable angina (SA). EMPs in platelet-poor plasma were measured flow cytometrically with combinations of fluorescent antibodies (anti-CD31, -51, -42), allowing distinction of EMPs from platelet microparticles (PMPs). Clinical subgroups of patients were correlated with EMP and PMP levels in blood. RESULTS: Two species of EMPs (CD31+ and CD51+) were evaluated. Both were significantly higher in patients with CAD than in control subjects. CD31+ EMP was higher in ACS than SA. Among patients with first MI, CD31+ EMP was higher in patients with MI than in patients with UA and was significantly higher than in patients with recurring MI. CD51+ EMP did not discriminate ACS from SA. A simultaneous assay of PMP showed correlation between EMPs and PMPs. However, PMPs did not discriminate patients with SA from control subjects. CONCLUSIONS: EMP assay appears promising for assessing EC injury in CAD.

Adult↗
PubMed2003

Factor VII/VIIa: a new antigen in the anti-phospholipid antibody syndrome.

We investigated antibodies to factor VII/VIIa (FVII/VIIa) and five other common target antigens in 33 patients with a history of anti-phospholipid syndrome (APS) and 50 healthy controls using an enzyme-linked immunosorbent assay (ELISA) technique. We found that antibody to FVII/VIIa, a previously unrecognized and common antigen in APS, was present in 67% of patients. Frequencies of antibodies to other target antigens were: anti-beta-2 glycoprotein 1 (anti-beta 2GP1), 88%; anti-cardiolipin (anti-CL), 76%; anti-phosphatidylethanolamine (anti-PE), 67%; anti-phosphatidylserine (anti-PS), 64%; and anti-phosphatidylcholine (anti-PC), 59%. Most patients had antibodies against multiple antigens, but a few were positive for only anti-beta 2GP1 (12%) or anti-CL (3%). Positivity for anti-FVII/VIIa was significantly associated with positivity for anti-PE, anti-PS and/or anti-PC (P < 0.05) but not anti-beta 2GP1. When frequencies of immunoglobulin G (IgG) versus immunoglobulin M (IgM) antibodies were compared, anti-beta 2GP1 IgG correlated with the lupus anticoagulant (P < 0.05) and was significantly more prevalent than IgM, but the reverse was seen for all other antigens. In arterial thrombosis, IgM was more prevalent for all antigens, and was significantly associated with FVII/VIIa, PE and PS, whereas in venous thrombosis, IgG was frequently prevalent, especially in association with FVII/VIIa, beta 2GP1 and CL. In summary, FVII/VIIa is a new and common antigen in APS. Anti-FVII/VIIa is often associated with anti-PE, anti-PS and anti-PC. The IgM class is more frequently associated with arterial thrombosis and the IgG class with venous thrombosis.

Adult↗
PubMed2003

Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation.

It has been suggested that endothelial apoptosis is a primary lesion in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). We tested this hypothesis by examining the phenotypic signatures of endothelial microparticles (EMP) in TTP patients. In addition, the effect of TTP plasma on microvascular endothelial cells (MVEC) in culture was further delineated. EMP released by endothelial cells (EC) express markers of the parent EC; EMP released in activation carry predominantly CD54 and CD62E, while those in apoptosis CD31 and CD105. We investigated EMP release in vitro and in TTP patients. Following incubation of MVEC with TTP plasma, EMP and EC were analysed by flow cytometry for the expression of CD31, CD51, CD54, CD62E, CD105, CD106 and von Willebrand factor (VWF) antigen. EMP were also analysed in 12 TTP patients. In both EC and EMP, CD62E and CD54 expression were increased 3- to 10-fold and 8- to 10-fold respectively. However, CD31 and CD105 were reduced 40-60% in EC but increased twofold in EMP. VWF expression was found in 55 +/- 15% of CD62E+ EMP. Markers of apoptosis were negative. In TTP patients, CD62E+ and CD31+/CD42b- EMP were markedly elevated, and preceded and correlated well with a rise in platelet counts and a fall in lactate dehydrogenase. CD62E+ EMP (60 +/- 20%) co-expressed VWF and CD62E. The ratio of CD31+/42b- to CD62E+ EMP exhibited a pattern consistent with activation. In conclusion, our studies indicate endothelial activation in TTP. EMP that co-express VWF and CD62E could play a role in the pathogenesis of TTP.

Apoptosis↗
PubMed2003

Elevated plasma endothelial microparticles in preeclampsia.

OBJECTIVE: The purpose of this study was to assess endothelial dysfunction in women with preeclampsia by measuring endothelial microparticles. STUDY DESIGN: A case-control study was conducted on 20 women with preeclampsia and 20 healthy pregnant women as control subjects. Endothelial microparticles were measured by flow cytometry with anti-CD31 and anti-CD42. CD31(+)/CD42(+) platelet microparticles were also quantified. RESULTS: Plasma endothelial microparticles levels were elevated significantly in women with preeclampsia as compared with control subjects (mean+/-SD and median [range]: 14,723+/-7,724 counts/microL and 12,378 counts/microL [1,442-33,772 counts/microL] vs 8406+/-2832 counts/microL and 9016 counts/microL [3,381-12,806 counts/microL]; P<.001). Plasma platelet microparticles levels were not different among cases compared to control subjects (10,751+/-6,114 counts/microL and 9463 counts/microL [3,000-23,895 counts/microL] vs 7871+/-4344 counts/microL and 6462 counts/microL [444-18,947 counts/microL]; P=.208). No significant correlation was found between plasma endothelial microparticles and mean arterial pressure in cases or control subjects. CONCLUSION: The elevation of endothelial microparticles in women with preeclampsia supports the endothelial injury theory in preeclampsia.

Adult↗
PubMed2003

Effects of severe hypertension on endothelial and platelet microparticles.

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 (P=0.002) and platelet (P=0.01) 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.

Adult↗
PubMed2002

Vascular dementia in patients with immune thrombocytopenic purpura.

INTRODUCTION: Platelets have been implicated in memory disorders but this has not been investigated in patients with immune or idiopathic thrombocytopenia (ITP). ITP is an autoimmune disorder in which autoantibodies bring about platelet destruction. We previously reported a group of ITP patients who manifested TIA-like syndrome and gradual memory loss leading to dementia: platelet microparticles (PMP), a marker of platelet activation, were often elevated, suggesting that procoagulant PMP released from stimulated platelets contributed to thrombosis in small vessels. We have expanded on those studies to better define the clinical, laboratory, and radiologic characteristics of this syndrome. MATERIALS AND METHODS: Twenty ITP patients with this syndrome were studied in comparison to twenty-three ITP patients without it (patient controls). Clinical and laboratory features were compared and radiologic images were analyzed. Factors influencing the rate of progression to advanced dementia were also investigated. RESULTS AND CONCLUSION: Recurring dizzy or weak spells, TIA-like syndrome, recent memory loss, and cognitive impairment were common initial complaints. In some, these symptoms progressed rapidly to dementia but was indolent in others. Progression was faster in those with splenectomy and higher platelet counts. MRI showed enhanced signal in subcortical, periventricular areas, consistent with ischemic small vessel disease. Compared to patient controls, bleeding was less frequent and platelet activation (increased PMP, CD62p) was more frequent in the study group. Thrombotic complications may occur in ITP, manifested as TIA-like syndrome or memory loss due to ischemic small vessel disease, progressing to vascular dementia. Memory disturbances associated with platelet disorders warrants further investigation.

Adult↗
PubMed2002

Agonist-induced capping of adhesion proteins and microparticle shedding in cultures of human renal microvascular endothelial cells.

Capping and release of membranous, small (< 1.5 microm) endothelial microparticles were quantified by immunofluorescence microscopy and flow cytometry after treatment of cultures of human renal microvascular endothelial cells with agonists tumor necrosis factor-alpha (TNF-alpha) or mitomycin C. For constitutive marker CD31, both agonist-treated attached, monolayer, and detached, free endothelial cells formed caps and released microparticles. TNF-alpha and mitomycin C induced dissimilar appearing CD31-containing caps after 3 h, followed by endothelial microparticle release after 6 h. The degree of capping correlated with increasing counts of released microparticles. For lymphokine-inducible CD54, TNF-alpha also induced CD54-containing caps and microparticle release, but mitomycin C failed to induce the expression of either entity. Neither capping nor microparticle release caused by TNF-alpha was part of an apoptotic pathway that involved caspase 3. Mitomycin C treatment of endothelial cells caused capping and microparticle release with a time course similar to TNF-alpha induction for 15 to 24 h, but assays for caspase 3 were positive, confirming the apoptotic action of mitomycin C. Membrane capping and microparticle release from endothelial cells are a convenient experimental model for studying protein movement, release of microparticles, and their possible biological significance.

Antibodies, Monoclonal↗