Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles

Wekesa, Anthony L; Cross, K.S.; O'Donovan, Orla; Dowdall, Joseph; O'Brien, Ottilia; Doyle, Melissa; Byrne, Lorraine; Phelan, John P.; Ross, Mark; Landers, R.; Harrison, Michael

doi:10.1016/j.ejvs.2014.08.007

Cited by 31 publications

(20 citation statements)

References 29 publications

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“…They are elevated in a range of vascular inflammatory 2 disorders and add to risk prediction in prospective studies when added to models 3 involving more established markers (Nozaki et al, 2009) . Recently, we have shown an 4 association between EMV and unstable atherosclerosis (Wekesa et al, 2014). EMV 5 impair endothelial dependent dilation, increase arterial stiffness, promote inflammation 6 and initiate coagulation (Chironi et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women

Wekesa

Doyle

Fitzmaurice

et al. 2016

Appl. Physiol. Nutr. Metab.

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Low-carbohydrate diets (LCD) are increasing in popularity, but their effect on vascular health has been questioned. Endothelial microvesicles (EMV) are membrane-derived vesicles with the potential to act as a sensitive prognostic biomarker of vascular health and endothelial function. The aim of this study was to examine the influence of a LCD on EMV and other endothelial biomarkers of protein origin. Twenty-four overweight women (age, 48.4 ± 0.6 years; height, 1.60 ± 0.07 m; body mass, 76.5 ± 9.1 kg; body mass index, 28.1 ± 2.7 kg·m−2; waist circumference, 84.1 ± 7.4 cm; mean ± standard deviation) were randomised to either 24 weeks on their normal diet (ND) or a LCD, after which they crossed over to 24 weeks on the alternative diet. Participants were assisted in reducing carbohydrate intake, but not below 40 g·day−1. Body composition and endothelial biomarkers were assessed at the crossover point and at the end of the study. Daily carbohydrate intake (87 ± 7 versus 179 ± 11 g) and the percentage of energy derived from carbohydrate (29% versus 44%) were lower (p < 0.05) on the LCD compared to the ND, but absolute fat and saturated fat intake were unchanged. Body mass and waist circumference were 3.7 ± 0.8 kg and 3.5 ± 1.0 cm lower (p < 0.05), respectively, after the LCD compared with the ND phases. CD31+CD41−EMV, soluble (s) thrombomodulin, sE-selectin, sP-selectin, serum amyloid A and C-reactive protein were lower (p < 0.05) after the LCD compared to the ND, but serum lipids and apolipoproteins were not different. EMV along with a range of endothelial and inflammatory biomarkers are reduced by a LCD that involves modest weight loss.

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Section: Introductionmentioning

confidence: 99%

Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women

Wekesa

Doyle

Fitzmaurice

et al. 2016

Appl. Physiol. Nutr. Metab.

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“…These reports have shown an increase in platelet-derived MPs (PMPs) in carotid atherosclerosis, 25 with higher levels of annexin V+ MPs associated with advanced carotid disease. 40 They have also suggested that levels of leukocyte-derived MPs and endothelial cell-derived MPs (EMPs) can be used to predict plaque instability. 32,40 However, the serial changes in levels of circulating MPs of various origins and their role in procoagulant activity (PCA) after CAS are still unknown.…”

mentioning

confidence: 99%

Increased blood cell phosphatidylserine exposure and circulating microparticles contribute to procoagulant activity after carotid artery stenting

Zhao¹,

Wu²,

Yu³

et al. 2017

Journal of Neurosurgery

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OBJECTIVE Phosphatidylserine (PS) is a major component of the inner leaflet of membrane bilayers. During cell activation or apoptosis, PS is externalized to the outer membrane, providing an important physiological signal necessary for the release of the microparticles (MPs) that are generated through the budding of cellular membranes. MPs express PS and membrane antigens that reflect their cellular origin. PS exposure on the cell surface and the release of MPs provide binding sites for factor Xa and prothrombinase complexes that promote thrombin formation. Relatively little is known about the role of PS exposure on blood cells and MPs in patients with internal carotid artery (ICA) stenosis who have undergone carotid artery stenting (CAS). The authors aimed to investigate the extent of PS exposure on blood cells and MPs and to define its role in procoagulant activity (PCA) in the 7 days following CAS. METHODS The study included patients with ICA stenosis who had undergone CAS (n = 70), matched patients who had undergone catheter angiography only (n = 30), and healthy controls (n = 30). Blood samples were collected from all patients just before the procedure after an overnight fast and at 2, 6, 24, 48, and 72 hours and 7 days after the CAS procedure. Blood was collected from healthy controls after an overnight fast. Phosphatidylserine-positive (PS+) MPs and blood cells were analyzed by flow cytometry, while PCA was assessed with clotting time analysis, purified coagulation complex assays, and fibrin formation assays. RESULTS The authors found that levels of PS+ blood cells and PS+ blood cell-derived MPs (platelets and platelet-derived MPs [PMPs], neutrophils and neutrophil-derived MPs [NMPs], monocytes and monocyte-derived MPs [MMPs], erythrocytes and erythrocyte-derived MPs [RMPs], and endothelial cells and endothelial cell-derived MPs [EMPs]) were increased in the 7 days following the CAS procedure. Specifically, elevation of PS exposure on platelets/PMPs, neutrophils/NMPs, and monocytes/MMPs was detected within 2 hours of CAS, whereas PS exposure was delayed on erythrocytes/RMPs and EMPs, with an increase detected 24 hours after CAS. In addition, PS+ platelets/PMPs peaked at 2 hours, while PS+ neutrophils/NMPs, monocytes/MMPs, and erythrocytes/RMPs peaked at 48 hours. After their peak, all persisted at levels above baseline for 7 days post-CAS. Moreover, the level of PS+ blood cells/MPs was correlated with shortened coagulation time and significantly increased intrinsic and extrinsic Xase, thrombin generation, and fibrin formation. Pretreatment of blood cells with lactadherin at their peak time point after CAS blocked PS, resulting in prolonged coagulation times, decreased procoagulant enzyme activation, and fibrin production. CONCLUSIONS The results of this study suggest that increased exposure of PS on blood cells and MPs may contribute to enhanced PCA in patients with ICA stenosis who have undergone CAS, explaining the risk of perioperative thromboembolic complications in these patients. PS on blood cells and...

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“…In addition, endothelial MP subsets (but not any vascular, inflammatory, or proteolytic molecular tested biomarker) were found to be higher in unstable than in stable plaque patients and the association was confirmed in univariate and multivariable analyses. 4 Although the message from Wekesa et al may be relevant, suggesting higher sensitivity of MP than other molecular biomarkers for predicting both the plaque instability (endothelial MP) and the presence of advanced carotid disease (platelet MPs), the results of the study should be interpreted with caution.…”

mentioning

confidence: 86%

“…The excised carotid plaques from the cases group were also analyzed with immunohistochemistry and graded for stability according to the inflammatory cell infiltration in the plaque and cap and the evidence of plaque rupture and surface thrombus as defined by Redgrave. 5 Wekesa et al 4 found significantly higher levels of subsets of platelet MP and annexin V þ MPs in carotid stenosis patients than in controls (p < .05) while the other soluble vascular inflammatory biomarkers tested in the same study (soluble intercellular adhesion molecule [sICAM-I], soluble vascular cell adhesion molecule [sVCAM-I], and serum amyloid A [SAA]) did not significantly differ. Furthermore, annexin V þ MP was independently associated with carotid stenosis in multivariable model analysis.…”

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confidence: 87%

“…1e3 MPs, also known as "microvescicles" or "ectosomes", 2 are large (50e1000 nm diameter) extracellular vesicles surrounded by a phospholipid bilayer that are released into extracellular space or circulation by direct budding from the plasma membrane of multiple lines of activated cells including platelets, endothelial cells, and leukocytes. In this issue of the European Journal of Vascular and Endovascular Surgery, Wekesa et al 4 performed a caseecontrol pilot study analyzing levels of endothelial MPs and platelet MPs in addition to other atherosclerotic molecular biomarkers in plasma from 42 patients undergoing CEA for symptomatic (n ¼ 37) and asymptomatic (n ¼ 4) carotid stenosis patients (cases) and from 73-age and sex-matched patients without carotid disease used as controls. The excised carotid plaques from the cases group were also analyzed with immunohistochemistry and graded for stability according to the inflammatory cell infiltration in the plaque and cap and the evidence of plaque rupture and surface thrombus as defined by Redgrave.…”

mentioning

confidence: 99%

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Commentary on: “Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles”

Rango

2014

European Journal of Vascular and Endovascular Surgery

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Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles

Abstract: EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers.

Cited by 31 publications

References 29 publications

Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women

Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women

Increased blood cell phosphatidylserine exposure and circulating microparticles contribute to procoagulant activity after carotid artery stenting

Commentary on: “Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles”

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