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Chantal M. Boulanger - One of the best experts on this subject based on the ideXlab platform.
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Mechanical
2016Co-Authors: Anne Clémence Vion, Anna A. Birukova, Chantal M. Boulanger, Konstantin G. BirukovAbstract:forces stimulate Endothelial Microparticle generation via caspase-dependent apoptosis-independent mechanis
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shear stress regulates Endothelial Microparticle release
Circulation Research, 2013Co-Authors: Anne Clémence Vion, Bhama Ramkhelawon, Xavier Loyer, Gilles Chironi, Cecile Devue, Gervaise Loirand, Alain Tedgui, Stephanie Lehoux, Chantal M. BoulangerAbstract:Rationale: Endothelial activation and apoptosis release membrane-shed Microparticles (EMP) that emerge as important biological effectors. Objective: As 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/cm2). EMP levels augmented with time in low- compared to high-SS conditions. This effect was sensitive to ERK1/2 and ROCK inhibitors, but unaffected by caspase inhibitors. Low SS-stimulated EMP release was associated with increased Endothelial ROCK and ERK1/2 activities and cytoskeletal reorganization. Over-expression of constitutively active RhoA stimulated EMP release under high SS. We also examined the effect of nitric oxide (NO) in mediating SS effects. L-NAME, but not D-NAME, increased high SS-induced EMP levels by 3-fold, whereas the NO donor SNAP decreased it. L-NAME and SNAP did not affect ROCK and ERK1/2 activities. Then, we investigated NO effect on membrane remodeling as 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 ROCK 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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mechanical forces stimulate Endothelial Microparticle generation via caspase dependent apoptosis independent mechanism
Pulmonary circulation, 2013Co-Authors: Anne Clémence Vion, Anna A. Birukova, Chantal M. Boulanger, Konstantin G. BirukovAbstract:AbstractMicroparticle release by vascular endothelium has been implicated in various cardiovascular pathologies. Ventilator-induced lung injury (VILI) is a life-threatening complication of mechanical ventilation at high tidal volumes associated with excessive mechanical stretch of pulmonary vascular Endothelial cells. However, a role of VILI-relevant levels of cyclic stretch in Microparticle generation by vascular endothelium remains unknown. We report Microparticle formation by human pulmonary Endothelial cells exposed to pathologic, but not physiologic, levels of mechanical stress. Stretch-induced Microparticle generation was not affected by cell co-treatment with inflammatory agents thrombin or bacterial wall lipopolysacharide. Neither the basal nor the pathologic cyclic stretch-induced Microparticle production was affected by Rho kinase and calpain inhibitors, but were instead abolished by caspase inhibitor. In contrast to lipopolysacharide, pathologic mechanical strain did not significantly induce ap...
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In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease
Hypertension (Dallas Tex. : 1979), 2007Co-Authors: Chantal M. Boulanger, Alain Tedgui, Nicolas Amabile, Alain P. Guerin, Bruno Pannier, Aurélie S. Leroyer, Ziad Mallat, Clément Nguyen, Gérard M. LondonAbstract:Shear stress is a major determinant of Endothelial apoptosis, but its role in the in vivo release of shed membrane Microparticles by Endothelial cells remains unknown. Thus, we sought to evaluate the possible relationship between circulating Endothelial Microparticle levels and laminar shear stress in end-stage renal disease patients with high cardiovascular risk, whose levels of Endothelial Microparticles are elevated. In 34 hemodialyzed patients, we analyzed the relationships between brachial artery and aortic shear stress and circulating Microparticles levels. Only Endothelial Microparticles were inversely correlated with laminar shear stress values (P
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Circulating Endothelial Microparticles Are Associated with Vascular Dysfunction in Patients with End-Stage Renal Failure
Journal of the American Society of Nephrology : JASN, 2005Co-Authors: Nicolas Amabile, Alain Tedgui, Alain P. Guerin, Aurélie S. Leroyer, Ziad Mallat, Clément Nguyen, Gérard M. London, Jacques Boddaert, Chantal M. BoulangerAbstract:Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because Microparticles can affect Endothelial cells, this study investigated the relationship between circulating Microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of Microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V Microparticles were increased compared with 32 healthy subjects, as were levels of Microparticles derived from Endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only Endothelial Microparticle levels correlated highly with loss of flow-mediated dilation (r 0.543; P 0.004), increased aortic pulse wave velocity (r 0.642, P < 0.0001), and increased common carotid artery augmentation index (r 0.463, P 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V Microparticle levels did not. In vitro, Microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas Microparticles from healthy subjects did not. Moreover, in vitro Endothelial dysfunction correlated with Endothelial-derived (r 0.891; P 0.003) but not platelet-derived Microparticle concentrations. In fact, Endothelial Microparticles alone decreased Endothelial nitric oxide release by 59 7% (P 0.025). This study suggests that circulating Microparticles of Endothelial origin are tightly associated with Endothelial dysfunction and arterial dysfunction in ESRF.
Nicolas Amabile - One of the best experts on this subject based on the ideXlab platform.
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abstract 171 Endothelial Microparticle levels and silent stroke in the framingham heart study
Stroke, 2018Co-Authors: Hugo J Aparicio, Nicolas Amabile, Jayandra J Himali, Matthew P Pase, Jose R Romero, Claudia L Satizabal, Susan Cheng, Martin G Larson, Charles Decarli, Thomas J WangAbstract:Introduction: Endothelial Microparticles (EMP) are membrane vesicles, with a characteristic diameter of 0.1-1.0μ, shed by Endothelial cells during cellular activation or apoptosis. EMP are associated with cardiovascular disease and risk factors, but data are lacking on the relations of EMP with subclinical vascular brain injury. Methods: We studied 487 individuals (mean age 66.9±8.8 years, 55% women) from the Framingham Offspring Cohort, who were free from clinical stroke. CD31+/CD41- EMP were identified and quantified using flow cytometry. Silent cerebral infarcts (SCI) were quantified as parenchymal lesions on brain MRI >3mm in size with characteristics of previous infarcts. Logistic regression models were used to investigate cross-sectional associations of EMP levels with prevalent SCI. We tested for interaction between EMP levels and statin use in their relationship with SCI. Results: SCI was observed in 49 (10%) participants. Figure 1 displays results of the logistic regression analysis. Circulating ...
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increased cd62e Endothelial Microparticle levels predict poor outcome in pulmonary hypertension patients
Journal of Heart and Lung Transplantation, 2009Co-Authors: Nicolas Amabile, Christian Heiss, Dana Mcglothlin, Eduardo J Rame, William Grossman, Teresa De Marco, Vivian Chang, Franca S Angeli, Lauren E Damon, Yerem YeghiazariansAbstract:Background: Endothelial and leukocytes-derived Microparticles (EMPs and LMPs, respectively) are increased in patients with pulmonary hypertension (PH). We hypothesized that the levels of circulating EMPs and LMPs could predict outcome in these patients. Methods: Patients undergoing right heart catheterization for untreated pre-capillary PH were eligible for the study. Baseline hemodynamics and biologic and clinical parameters were measured at the time of enrollment. Measurements of CD62e, CD144 and CD31/CD41 EMPs and CD45 LMPs were performed using flow cytometry in venous platelet-free plasma samples. After inclusion, patients were treated at the discretion of the physician and prospectively followed for 12 months. The primary end-point was the combined occurrence of death and re-admission for right heart failure (RHF) or worsening of RHF symptoms. Results: Seven of 21 patients (mean age 54.1 3.5 years, 62% female) experienced the primary end-point during the study period. These patients had higher baseline levels of CD62e EMPs, LMPs and hsCRP (high sensitivity C-reactive protein) compared to patients without events (p 0.05), whereas no difference was observed for other Microparticles and functional and hemodynamics parameters. Receiver operating curve analysis showed that baseline CD62e EMPs levels of 353 events/l predicted clinical complications. Kaplan‐Meier analysis revealed that patients with baseline CD62e EMPs above this cut-off value had a significantly worse prognosis compared with those subjects who had levels below this cut-off (p 0.02, log-rank statistics). Conclusions: Elevated levels of circulating CD62e EMPs but not LMPs in PH patients prior to treatment are associated with adverse clinical events. Assessment of CD62e EMPs levels may represent a new tool for stratification of PH patients. J Heart Lung Transplant 2009;28:1081‐6. Copyright © 2009 by the International Society for Heart and Lung Transplantation.
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circulating Endothelial Microparticle levels predict hemodynamic severity of pulmonary hypertension
American Journal of Respiratory and Critical Care Medicine, 2008Co-Authors: Nicolas Amabile, Christian Heiss, Wendy May Real, Petros Minasi, Dana Mcglothlin, Eduardo J Rame, William Grossman, Teresa De Marco, Yerem YeghiazariansAbstract:Rationale: Circulating Microparticles (MPs) are submicron membrane fragments shed from damaged or activated vascular cells. Endothelial MPs are a biological marker of dysfunctional endothelium. Vascular remodeling and Endothelial dysfunction are involved in pulmonary hypertension (PH). Objectives: We tested the hypothesis that circulating MPs are increased in patients with PH and that identifiable subgroups of MPs predict the hemodynamic severity of this condition progression. Methods :P atients (n5 24; age, 54 6 4 yr) undergoing right heart catheterization for precapillary PH without any endothelium-active vasodilator therapy participated in the study. Age- and sex-matched healthycontrolsubjects(n 520)wereincluded.Endothelial(PECAM 1 [CD31 1 ]/CD41 2 ,VE-cadherin 1 [CD144 1 ],andE-selectin 1 [CD62e 1 ]), platelet (CD41 1 ), leukocyte-derived (CD45 1 ), and annexin V 1 MPs weremeasuredbyflowcytometryinplatelet-freeplasmafromvenous blood. Measurements and Main Results: Levels of circulating Endothelial PECAM 1 , VE-cadherin 1 , E-selectin 1 , and leukocyte-derived MPs, but not platelet and annexin V1 MPs, were increased in subjects with PH compared with control subjects (P , 0.01 each). PECAM1 and VEcadherin1 MP levels significantly correlated with mean pulmonary artery pressure (r 5 0.92 and r 5 0.87, respectively), pulmonary vascular resistance (r 5 0.78 and r 5 0.73), and mean right atrial pressure(r 5 0.43,andr 5 0.46) andcorrelated inverselywithcardiac index (r 52 0.59 and r 52 0.52). These relationships were not observed for other MP subgroups, and persisted in multivariate analysis after adjustment for confounding factors. Conclusions: In subjects with precapillary PH, levels of circulating EndothelialandleukocyteMPswereincreasedcomparedwithcontrol subjects. In addition, levels of PECAM1 and VE-cadherin1 ,b ut not E-selectin 1 , Endothelial MPs predicted hemodynamic severity of
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In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease
Hypertension (Dallas Tex. : 1979), 2007Co-Authors: Chantal M. Boulanger, Alain Tedgui, Nicolas Amabile, Alain P. Guerin, Bruno Pannier, Aurélie S. Leroyer, Ziad Mallat, Clément Nguyen, Gérard M. LondonAbstract:Shear stress is a major determinant of Endothelial apoptosis, but its role in the in vivo release of shed membrane Microparticles by Endothelial cells remains unknown. Thus, we sought to evaluate the possible relationship between circulating Endothelial Microparticle levels and laminar shear stress in end-stage renal disease patients with high cardiovascular risk, whose levels of Endothelial Microparticles are elevated. In 34 hemodialyzed patients, we analyzed the relationships between brachial artery and aortic shear stress and circulating Microparticles levels. Only Endothelial Microparticles were inversely correlated with laminar shear stress values (P
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Circulating Endothelial Microparticles Are Associated with Vascular Dysfunction in Patients with End-Stage Renal Failure
Journal of the American Society of Nephrology : JASN, 2005Co-Authors: Nicolas Amabile, Alain Tedgui, Alain P. Guerin, Aurélie S. Leroyer, Ziad Mallat, Clément Nguyen, Gérard M. London, Jacques Boddaert, Chantal M. BoulangerAbstract:Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because Microparticles can affect Endothelial cells, this study investigated the relationship between circulating Microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of Microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V Microparticles were increased compared with 32 healthy subjects, as were levels of Microparticles derived from Endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only Endothelial Microparticle levels correlated highly with loss of flow-mediated dilation (r 0.543; P 0.004), increased aortic pulse wave velocity (r 0.642, P < 0.0001), and increased common carotid artery augmentation index (r 0.463, P 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V Microparticle levels did not. In vitro, Microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas Microparticles from healthy subjects did not. Moreover, in vitro Endothelial dysfunction correlated with Endothelial-derived (r 0.891; P 0.003) but not platelet-derived Microparticle concentrations. In fact, Endothelial Microparticles alone decreased Endothelial nitric oxide release by 59 7% (P 0.025). This study suggests that circulating Microparticles of Endothelial origin are tightly associated with Endothelial dysfunction and arterial dysfunction in ESRF.
Nikos Werner - One of the best experts on this subject based on the ideXlab platform.
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Endothelial Microparticle promoted inhibition of vascular remodeling is abrogated under hyperglycaemic conditions
Journal of Molecular and Cellular Cardiology, 2017Co-Authors: Felix Jansen, Andreas Zietzer, Tobias Stumpf, Anna Flender, Theresa Schmitz, Georg Nickenig, Nikos WernerAbstract:Abstract Background Endothelial Microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells. Methods and results EMPs were generated from human coronary Endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMPs were defined as ‘hyperglycaemic’ EMPs (hgEMPs) and their miRNA transfer capacity and functional effects were compared with EMPs generated from ‘healthy’ untreated HCAECs. In vitro, the intercellular transfer of antiproliferative miRNA-126-3p from ECs to VSMCs via EMPs was significantly reduced under hyperglycaemic conditions. Additionally, EMP-mediated inhibition of the miRNA-126-3p target LRP6 and of VSMC migration and proliferation was abrogated, when hgEMPs were used. In vivo, the inhibitory effect of EMPs on neointima formation, VSMC proliferation and macrophage infiltration was abolished in mice treated with hgEMPs. Conclusion Pathological hyperglycaemic conditions weaken potentially protective intercellular communication mechanisms by affecting EMP content and function.
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Endothelial Microparticle-mediated transfer of microRNA126 promotes vascular Endothelial cell repair via SPRED1 and is abrogated in glucose-damaged Endothelial Microparticles
European Heart Journal, 2013Co-Authors: F. Jansen, Georg Nickenig, X. Yang, M. Hölscher, Nikos WernerAbstract:Introduction: Repair of the endothelium after vascular injury is crucial for preserving Endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of Endothelial cell repair are largely unknown. Here, we sought to investigate whether Endothelial Microparticles (EMP), released from apoptotic Endothelial cells (ECs), influence EC repair. Methods and results: EMP were generated from human coronary Endothelial cells (HCAEC) and characterized by confocal microscopy and flow cytometry. Systemic treatment of mice with EMP after electrical denudation of the endothelium accelerated reEndothelialization in vivo (29.81±2.31 vs. 50.71±9.84, p
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Endothelial Microparticle mediated transfer of microrna126 promotes vascular Endothelial cell repair via spred1 and is abrogated in glucose damaged Endothelial Microparticles
European Heart Journal, 2013Co-Authors: F. Jansen, Georg Nickenig, X. Yang, M. Hölscher, Nikos WernerAbstract:Introduction: Repair of the endothelium after vascular injury is crucial for preserving Endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of Endothelial cell repair are largely unknown. Here, we sought to investigate whether Endothelial Microparticles (EMP), released from apoptotic Endothelial cells (ECs), influence EC repair. Methods and results: EMP were generated from human coronary Endothelial cells (HCAEC) and characterized by confocal microscopy and flow cytometry. Systemic treatment of mice with EMP after electrical denudation of the endothelium accelerated reEndothelialization in vivo (29.81±2.31 vs. 50.71±9.84, p<0.01, n=12-14). Human EMP incorporation by murine ECs was confirmed in subsequent experiments using flow cutometry and immunofluorescence. In vitro experiments revealed that EMP uptake in ECs promote EC migration (82.02±15.72 vs. 37.05±19.00, p<0.01, n=6) and proliferation (160.8±24.67 vs. 100.0±26.86, n=6), both critical steps in Endothelial repair. In order to dissect the underlying mechanisms, Taqman microRNA-array was performed and microRNA (miR)-126 was identified as the predominantly expressed miR in EMP (n=3). Following experiments demonstrated that miR-126 was transported into recipient HCAEC by EMP and functionally regulated the target protein sprouty-related, EVH1 domain containing 1 (Spred1). Genetic downregulation of Spred1 in HCAEC increased EC migration and proliferation capacity. Knockdown of miR-126 in EMP abrogated EMP-mediated effects on HCAEC migration and proliferation in vitro and reEndothelialization in vivo, confirming the crucial role of miR-126 in EMP-mediated Endothelial regeneration. Next, we tested whether EMP generated under pathological hyperglycaemic conditions (defined as "injured" EMP, (iEMP)) differed in miR expression and function from EMP. Interestingly, Taqman microRNA-array analysis revelaed that miR-126 was the strongest regulated miR between iEMP and EMP (n=3). Subsequently, iEMP derived from glucose-treated ECs showed reduced Endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating Microparticles from 176 patients with stable coronary artery disease with and without diabetes revealed a significantly reduced miR-126 expression in circulating Microparticles from diabetic patients. Conclusion: Endothelial Microparticles promote vascular Endothelial repair by delivering functional microRNA-126 into recipient cells. This leads to downregulation of target protein Spred1 and improves migratory and proliferative EC capacity with subsequent improvement of EC repair. In pathological hyperglycaemic conditions, EMP-mediated miR-126 induced EC repair is altered.
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Endothelial RIG-I activation impairs Endothelial function
Biochemical and Biophysical Research Communications, 2012Co-Authors: Tobias Asdonk, Georg Nickenig, Nikos Werner, Inga Motz, Christoph Coch, Winfried Barchet, Gunther Hartmann, Sebastian ZimmerAbstract:Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs Endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in Endothelial biology in a proatherogenic manner. Here, we analyzed the impact of Endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular Endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating Endothelial Microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent Endothelial biology, cultured human coronary Endothelial cells (HCAEC) and Endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cellmore » types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to Endothelial dysfunction. RIG-I induced Endothelial damage could therefore be an important pathway in atherogenesis.« less
Lilach O Lerman - One of the best experts on this subject based on the ideXlab platform.
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Loss of Renal Peritubular Capillaries in Hypertensive Patients Is Detectable by Urinary Endothelial Microparticle Levels
Hypertension, 2018Co-Authors: Adrian Santelli, Abdelrhman Abumoawad, Alfonso Eirin, Christopher M Ferguson, John R Woollard, Stephen C. Textor, Amir Lerman, Amrutesh S. Puranik, Lilach O LermanAbstract:Hypertension, an important cause of chronic kidney disease, is characterized by peritubular capillary (PTC) loss. Circulating levels of Endothelial Microparticles (EMPs) reflect systemic endothelia...
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loss of renal peritubular capillaries in hypertensive patients is detectable by urinary Endothelial Microparticle levels
Hypertension, 2018Co-Authors: In O Sun, Adrian Santelli, Abdelrhman Abumoawad, Alfonso Eirin, Christopher M Ferguson, John R Woollard, Stephen C. Textor, Amir Lerman, Amrutesh S. Puranik, Lilach O LermanAbstract:Hypertension, an important cause of chronic kidney disease, is characterized by peritubular capillary (PTC) loss. Circulating levels of Endothelial Microparticles (EMPs) reflect systemic Endothelial injury. We hypothesized that systemic and urinary PTC-EMPs levels would reflect renal microvascular injury in hypertensive patients. We prospectively measured by flow cytometry renal vein, inferior vena cava, and urinary levels of EMPs in essential (n=14) and renovascular (RVH; n=24) hypertensive patients and compared them with peripheral blood and urinary levels in healthy volunteers (n=14). PTC-EMPs were identified as urinary exosomes positive for the PTC marker plasmalemmal-vesicle-associated protein. In 7 RVH patients, PTC and fibrosis were also quantified in renal biopsy, and in 18 RVH patients, PTC-EMPs were measured again 3 months after continued medical therapy with or without stenting (n=9 each). Renal vein and systemic PTC-EMPs levels were not different among the groups, whereas their urinary levels were elevated in both RVH and essential hypertension versus healthy volunteers (56.8%±12.7% and 62.8%±10.7% versus 34.0%±17.8%; both P≤0.001). Urinary PTC-EMPs levels correlated directly with blood pressure and inversely with estimated glomerular filtration rate. Furthermore, in RVH, urinary PTC-EMPs levels correlated directly with stenotic kidney hypoxia, histological PTC count, and fibrosis and inversely with cortical perfusion. Three months after treatment, the change in urinary PTC-EMPs levels correlated inversely with a change in renal function ( r=-0.582; P=0.011). Therefore, urinary PTC-EMPs levels are increased in hypertensive patients and may reflect renal microcirculation injury, whereas systemic PTC-EMPs levels are unchanged. Urinary PTC-EMPs may be useful as novel biomarkers of intrarenal capillary loss.
Felix Jansen - One of the best experts on this subject based on the ideXlab platform.
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Endothelial Microparticle promoted inhibition of vascular remodeling is abrogated under hyperglycaemic conditions
Journal of Molecular and Cellular Cardiology, 2017Co-Authors: Felix Jansen, Andreas Zietzer, Tobias Stumpf, Anna Flender, Theresa Schmitz, Georg Nickenig, Nikos WernerAbstract:Abstract Background Endothelial Microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells. Methods and results EMPs were generated from human coronary Endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMPs were defined as ‘hyperglycaemic’ EMPs (hgEMPs) and their miRNA transfer capacity and functional effects were compared with EMPs generated from ‘healthy’ untreated HCAECs. In vitro, the intercellular transfer of antiproliferative miRNA-126-3p from ECs to VSMCs via EMPs was significantly reduced under hyperglycaemic conditions. Additionally, EMP-mediated inhibition of the miRNA-126-3p target LRP6 and of VSMC migration and proliferation was abrogated, when hgEMPs were used. In vivo, the inhibitory effect of EMPs on neointima formation, VSMC proliferation and macrophage infiltration was abolished in mice treated with hgEMPs. Conclusion Pathological hyperglycaemic conditions weaken potentially protective intercellular communication mechanisms by affecting EMP content and function.
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Endothelial Microparticle mediated transfer of microrna 126 promotes vascular Endothelial cell repair via spred1 and is abrogated in glucose damaged Endothelial Microparticles
Circulation, 2013Co-Authors: Felix Jansen, Theresa Schmitz, Xiaoyan Yang, Bernardo S Franklin, Marion Hoelscher, Arianna Cattelan, Sebastian Proebsting, Daniela Wenzel, Sarah Vosen, Bernd K. FleischmannAbstract:Background—Repair of the endothelium after vascular injury is crucial for preserving Endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of Endothelial cell repair are largely unknown. We sought to investigate whether Endothelial Microparticles (EMPs), released from apoptotic Endothelial cells (ECs), influence EC repair. Methods and Results—Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reEndothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in Endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery Endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-conta...
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Endothelial Microparticle–Mediated Transfer of MicroRNA-126 Promotes Vascular Endothelial Cell Repair via SPRED1 and Is Abrogated in Glucose-Damaged Endothelial Microparticles
Circulation, 2013Co-Authors: Felix Jansen, Theresa Schmitz, Xiaoyan Yang, Bernardo S Franklin, Marion Hoelscher, Arianna Cattelan, Sebastian Proebsting, Daniela Wenzel, Sarah Vosen, Bernd K. FleischmannAbstract:Background—Repair of the endothelium after vascular injury is crucial for preserving Endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of Endothelial cell repair are largely unknown. We sought to investigate whether Endothelial Microparticles (EMPs), released from apoptotic Endothelial cells (ECs), influence EC repair. Methods and Results—Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reEndothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in Endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery Endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-conta...
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Endothelial Microparticle uptake in target cells is annexin i phosphatidylserine receptor dependent and prevents apoptosis
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Felix Jansen, Xiaoyan Yang, Friedrich Felix Hoyer, Kathrin Paul, Nadine Heiermann, Marc Ulrich Becher, Nebal Abu Hussein, Moritz Kebschull, Jorg Bedorf, Bernardo S FranklinAbstract:Objective— Endothelial Microparticles (EMP) are released from activated or apoptotic cells, but their effect on target cells and the exact way of incorporation are largely unknown. We sought to determine the uptake mechanism and the biological effect of EMP on Endothelial and Endothelial-regenerating cells. Methods and Results— EMP were generated from starved Endothelial cells and isolated by ultracentrifugation. Caspase 3 activity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that EMP protect target Endothelial cells against apoptosis in a dose-dependent manner. Proteomic analysis was performed to identify molecules contained in EMP, which might be involved in EMP uptake. Expression of annexin I in EMP was found and confirmed by Western blot, whereas the corresponding receptor phosphatidylserine receptor was present on Endothelial target cells. Silencing either annexin I on EMP or phosphatidylserine receptor on target cells using small interfering RNA showed that the uptake of EMP by human coronary artery Endothelial cells is annexin I/phosphatidylserine receptor dependent. Annexin I–downregulated EMP abrogated the EMP-mediated protection against apoptosis of Endothelial target cells. p38 activation was found to mediate camptothecin-induced apoptosis. Finally, human coronary artery Endothelial cells pretreated with EMP inhibited camptothecin-induced p38 activation. Conclusion— EMP are incorporated by Endothelial cells in an annexin I/phosphatidylserine receptor–dependent manner and protect target cells against apoptosis. Inhibition of p38 activity is involved in EMP-mediated protection against apoptosis.