In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease

Boulanger, Chantal M.; Amabile, Nicolas; Guérin, Alain P.; Pannier, Bruno; Leroyer, Aurélie S.; Mallat, Ziad; Nguyen, Claire; Tedgui, Alain; London, Gérard M.

doi:10.1161/01.hyp.0000259667.22309.df

Cited by 161 publications

(119 citation statements)

References 41 publications

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“…In the present study, all patients with CKD-AP had chronic kidney vascular disease associated with CKD. Accordingly, our findings are supported by those of previous reports 42,43) . The circulating MP levels are strongly associated with acute coronary syndrome 31) and diabetes mellitus 33) , both of which are indicators of CAD and atherosclerosis.…”

Section: Conflicts Of Interestsupporting

confidence: 94%

“…Furthermore, although the creatinine level ( Table 4) was found to be significantly correlated with high circulating levels of EDAp-MPs and PDAp-MPs, neither a reduced eGFR nor increased creatinine level (an indicator of CKD) were identified to be independently predictive of an increased circulating level of MPs. A previous study demonstrated that, even in patients with severe CKD (end-stage renal disease on hemodialysis), the circulating MP levels were significantly increased only in the presence of reduced whole blood viscosity and shearing stress 42) . Other authors have documented elevated levels of MPs due to acute vascular damage, rather than chronic vasculitis, resulting from renal disease 43) .…”

Section: Conflicts Of Interestmentioning

confidence: 99%

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Levels of Circulating Microparticles in Patients with Chronic Cardiorenal Disease

Chen

Wallace

et al. 2015

JAT

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Aim: Cardiac and renal diseases are common disorders that frequently coexist. We tested the hypothesis that the levels of circulating endothelial-derived apoptotic microparticles (EDA-MPs; CD31 CD42b AN V ) and platelet-derived apoptotic microparticles (PDA-MPs; CD31 CD42b AN V ) are useful biomarkers for predicting the presence of cardiorenal disease (CRD). Methods: A total of 68 patients with chronic kidney disease (CKD) and angina pectoris (CKD-AP) undergoing cardiac catheterization were prospectively enrolled into group 1, 10 patients with coronary artery disease (CAD) without CKD were enrolled into group 2 (CAD CKD ) and 10 patients without CAD and CKD were enrolled into group 3 (CAD CKD ). Results: The serum creatinine levels were significantly higher, whereas the estimated glomerular filtration rates (eGFRs) were significantly lower, in group 1 than in the other two groups (all p 0.02). The circulating levels of EDA-MPs and PDA-MPs did not differ between the patients with and without CKD (all p 0.2). However, the circulating levels of EDA-MPs and PDA-MPs were significantly higher in group 2 than in groups 1 and 3 (all p 0.03). In addition, differences were noted in the circulating EDA-MP and PDA-MP levels between groups 1 and 3, although without statistical significance (all p 0.09). Meanwhile, among the CKD patients, the subgroup analysis showed that the levels of MPs were significantly higher in those with CAD than in those without (all p 0.001), while a multivariate analysis demonstrated that CAD was the only factor independently predictive of high levels of circulating EDA-MPs and PDA-MPs (p 0.033). Conclusions:The link with increased circulating levels of MPs is more consistent in patients with CAD than in those with CKD. J Atheroscler Thromb, 2015; 22: 247-256.

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Section: Conflicts Of Interestsupporting

confidence: 94%

Section: Conflicts Of Interestmentioning

confidence: 99%

Levels of Circulating Microparticles in Patients with Chronic Cardiorenal Disease

Chen

Wallace

et al. 2015

JAT

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“…Renal disease, [25][26][27] hypertension, 28 thrombotic thrombocytopenic purpura, 29 and pregnancy 30 promote the release of endothelial microparticles. A wide range of diseases and insults are also associated with the generation of platelet and leukocyte microparticles.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Renner¹,

Klawitter²,

Goldberg³

et al. 2013

Journal of the American Society of Nephrology

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Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases.

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“…A number of recent studies have shown that diseases of the vasculature and kidneys, including CKD, are associated with increased numbers of circulating endothelial microparticles 17, 18, 19, 20, 21, 22. We have previously reported that the microparticles released from endothelial cells can, under some conditions, activate the complement system, and that generation of complement‐activating microparticles is associated with vascular and renal injury in mice 23.…”

Section: Introductionmentioning

confidence: 98%

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease

Jalal

Renner

Laskowski

et al. 2018

JAHA

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BackgroundEndothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.Methods and ResultsWe analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow–mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post–kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow–mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro.ConclusionThe alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD‐associated vascular disease.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.

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In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease

Cited by 161 publications

References 41 publications

Levels of Circulating Microparticles in Patients with Chronic Cardiorenal Disease

Levels of Circulating Microparticles in Patients with Chronic Cardiorenal Disease

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease

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