Circulating microparticles may influence early carotid artery remodeling

Chironi, Gilles; Simon, Alain; Boulanger, Chantal M.; Dignat-George, Françoise; Hugel, Bénédicte; Mégnien, Jean-Louis; Lefort, Muriel; Freyssinet, Jean‐Marie; Tedgui, Alain

doi:10.1097/hjh.0b013e328335d0a8

Cited by 36 publications

(25 citation statements)

References 24 publications

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“…Circulating levels of leukocyte-derived MPs, possibly reflecting the increased vascular inflammation, are independently associated with subclinical atherosclerosis 164 and inward carotid artery remodeling in asymptomatic subjects. 165 Several studies identify plasma levels of endothelial MPs as a surrogate marker of vascular function. In patients with established endothelial dysfunction, levels of circulating endothelial MPs are inversely correlated with the amplitude of flow-mediated dilatation, independently of age and pressure.…”

Section: Microparticles: Biomarkers Of Cardiovascular Disease Progresmentioning

confidence: 99%

Microparticles, Vascular Function, and Atherothrombosis

Rautou

Vion

Amabile

et al. 2011

Circulation Research

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340

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Section: Microparticles: Biomarkers Of Cardiovascular Disease Progresmentioning

confidence: 99%

Microparticles, Vascular Function, and Atherothrombosis

Rautou

Vion

Amabile

et al. 2011

Circulation Research

Self Cite

340

283

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“…The study approved by the local ethical committee included 74 asymptomatic subjects without cardiovascular disease, 10,11 and their cardiovascular risk factors were assessed according to current guidelines. 12,13 The risk of coronary heart disease was estimated by entering age, male sex, systolic pressure, total and high-density lipoproteincholesterol, presence or absence of smoking in the Framingham model equations, 13 and defined the 10-year coronary risk as low (<10%), intermediate (10%-20%), or high (>20%).…”

Section: Clinical Studymentioning

confidence: 99%

Shear Stress Regulates Endothelial Microparticle Release

Vion

Ramkhelawon

Loyer

et al. 2013

Circulation Research

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Rationale: Endothelial activation and apoptosis release membrane-shed microparticles (EMP) that emerge as important biological effectors. Objective: Because laminar shear stress (SS) is a major physiological regulator of endothelial survival, we tested the hypothesis that SS regulates EMP release. Methods and Results: EMP levels were quantified by flow cytometry in medium of endothelial cells subjected to low or high SS (2 and 20 dyne/cm 2 ). EMP levels augmented with time in low SS conditions compared with high SS conditions. This effect was sensitive to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Rho kinases inhibitors but unaffected by caspase inhibitors. Low SS-stimulated EMP release was associated with increased endothelial Rho kinases and ERK1/2 activities and cytoskeletal reorganization. Overexpression of constitutively active RhoA stimulated EMP release under high SS. We also examined the effect of nitric oxide (NO) in mediating SS effects. L-NG-nitroarginine methyl ester (L-NAME), but not D-NG-nitroarginine methyl ester, increased high SS-induced EMP levels by 3-fold, whereas the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) decreased it. L-NAME and SNAP did not affect Rho kinases and ERK1/2 activities. Then, we investigated NO effect on membrane remodeling because microparticle release is abolished in ABCA1-deficient cells. ABCA1 expression, which was greater under low SS than under high SS, was augmented by L-NAME under high SS and decreased by SNAP under low SS conditions. Conclusions: Altogether, these results demonstrate that sustained atheroprone low SS stimulates EMP release through activation of Rho kinases and ERK1/2 pathways, whereas atheroprotective high SS limits EMP release in a NO-dependent regulation of ABCA1 expression and of cytoskeletal reorganization. These findings, therefore, identify endothelial SS as a physiological regulator of microparticle release.

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“…Calcium plays a crucial role in release, initiating the rapid loss of membrane phospholipids asymmetry and dissociation of actin from membrane glycoproteins (VanWijk et al 2003; Burnier et al 2009). MPs originating from platelets, erythrocytes, leukocytes and endothelial cells have been related to vascular function, remodeling, angiogenesis, hemostasis, thrombosis and cardiovascular diseases such as atherosclerosis and collagen vascular disorders (Nguyen et al 1998; VanWijk et al 2003; Martinez et al 2005; Shah et al 2008; Burnier et al 2009; Bobik 2010; Chironi et al 2010). More recently, smooth muscle cells were identified as a source of MPs, which seem to be active mainly within the vascular wall (Schecter et al 2000; Brisset et al 2003; Aras et al 2004; Essayagh et al 2005; Stampfuss et al 2006; Leroyer et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Transglutaminase 2 is secreted from smooth muscle cells by transamidation-dependent microparticle formation

et al. 2011

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Transglutaminase 2 (TG2) is a pleiotropic enzyme involved in both intra- and extracellular processes. In the extracellular matrix, TG2 stabilizes the matrix by both covalent cross-linking and disulfide isomerase activity. These functions become especially apparent during matrix remodeling as seen in wound healing, tumor development and vascular remodeling. However, TG2 lacks the signal sequence for a classical secretory mechanism, and the cellular mechanism of TG2 secretion is currently unknown. We developed a green fluorescent TG2 fusion protein to study the hypothesis that TG2 is secreted via microparticles. Characterization of TG2/eGFP, using HEK/293T cells with a low endogenous TG2 expression, showed that cross-linking activity and fibronectin binding were unaffected. Transfection of TG2/eGFP into smooth muscle cells resulted in the formation of microparticles (MPs) enriched in TG2, as detected both by immunofluorescent microscopy and flow cytometry. The fraction of TG2-positive MPs was significantly lower for cross-linking-deficient mutants of TG2, implicating a functional role for TG2 in the formation of MPs. In conclusion, the current data suggest that TG2 is secreted from the cell via microparticles through a process regulated by TG2 cross-linking.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-011-1010-3) contains supplementary material, which is available to authorized users.

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Circulating microparticles may influence early carotid artery remodeling

Abstract: Increased levels of leukocyte and endothelial-derived microparticles are associated with carotid inward remodeling in individuals with the greatest IMT before atherosclerosis is detectable.

Cited by 36 publications

References 24 publications

Microparticles, Vascular Function, and Atherothrombosis

Microparticles, Vascular Function, and Atherothrombosis

Shear Stress Regulates Endothelial Microparticle Release

Transglutaminase 2 is secreted from smooth muscle cells by transamidation-dependent microparticle formation

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