Jeremy Bellien

Centre Hospitalier Universitaire Rouen, Rouen, Upper Normandy, France

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Publications (47)145.24 Total impact

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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a renal hereditary disorder associated with increased cardiovascular mortality, due to mutations in polycystin-1 and polycystin-2 genes. Endothelial polycystin-deficient cells have an altered mechanosensitivity to fluid shear stress and subsequent deficit in calcium-induced nitric oxide release, prevented by dopamine receptor stimulation. However, the impact of polycystin deficiency on endothelial function in ADPKD patients is still largely unknown. Here we assessed endothelium-dependent flow-mediated dilatation in 21 normotensive ADPKD patients and 21 healthy control subjects, during sustained (hand skin heating) and transient (postischemic hyperemia) flow stimulation. Flow-mediated dilatation was less marked in ADPKD patients than in controls during heating, but it was similar during postischemic hyperemia. There was no difference in endothelium-independent dilatation in response to glyceryl trinitrate. Local plasma nitrite, an indicator of nitric oxide availability, increased during heating in controls but not in patients. Brachial infusion of dopamine in a subset of ADPKD patients stimulated plasma nitrite increase during heating and improved flow-mediated dilatation. Thus, ADPKD patients display a loss of nitric oxide release and an associated reduction in endothelium-dependent dilatation of conduit arteries during sustained blood flow increase. The correction of these anomalies by dopamine suggests future therapeutic strategies that could reduce the occurrence of cardiovascular events in ADPKD.Kidney International advance online publication, 16 July 2014; doi:10.1038/ki.2014.241.
    Kidney international. 07/2014;
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    ABSTRACT: Objective. To assess the role of Toll-like receptors (TLRs) in antiphospholipid antibody (aPL)-mediated vascular abnormalities in patients with primary arterial antiphospholipid syndrome (APS).Methods. Forty eight subjects participated in the study. Arterial function and structure and TLR pathway activation were determined in primary arterial APS patients and frequency-matched controls. The pathogenic effects of aPL isolated from patients were assessed in wild-type and TLR knockout mice.Results. APS patients displayed endothelial dysfunction, arterial stiffening and hypertrophy, as shown by decreased brachial artery endothelium-dependent flow-mediated dilatation (FMD) and increased aortic pulse wave velocity and carotid intima-media thickness (IMT) as compared with controls. Plasma samples from APS patients revealed decreased NO availability and a pro-oxidative, pro-inflammatory and pro-thrombotic state illustrated by a decrease in nitrite and an increase in lipid peroxidation, TNF-α and tissue factor (TF) levels. Furthermore, TLR pathway activation was demonstrated in APS patients with increased TLR2 and TLR4 mRNA expression and protein levels of activated TLR transduction protein IRAK1 in peripheral blood mononuclear cells. Moreover, agonist-stimulated cell-surface expression of TLR2 and TLR4 in circulating monocytes was higher in APS patients than in controls. These changes were positively associated with IMT and negatively with FMD. Finally, aPL injection decreased mesenteric endothelium-dependent relaxations and increased TF expression in wild-type but not in TLR2 or TLR4 knockout mice.Conclusion. This translational study supports the role of TLR2 and TLR4 in mediating vascular abnormalities in primary arterial APS patients. TLRs, thus constitute a promising pharmacological target to prevent the cardiovascular complications in APS. © 2014 American College of Rheumatology.
    Arthritis & Rheumatology. 07/2014;
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    ABSTRACT: Objective Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid, notably in endothelial cells, and display attractive metabolic, vasodilatory and anti-inflammatory properties. We demonstrated previously that inhibiting EET degradation mediated by soluble epoxide hydrolase (sEH) reduces hypertension and heart failure, and others reported that it improves glucose homeostasis in type 2 diabetes. However, the impact of such strategy on target organ damage in diabetes remains to be clarified. Materials and methods The pharmacological sEH inhibitor t-AUCB (10 mg/l in drinking water) was administered for 8 weeks in mice subjected to a high-fat diet (HFD, 60% fat) for 16 weeks. Mice on control chow diet (10% fat), non-treated HFD mice and HFD mice treated with glibenclamide (80 mg/l) served as controls. Results Glibenclamide and t-AUCB similarly prevented the increased fasting glycemia in HFD mice (Control: 5.4±0.2; HFD: 8.0±0.8; HFD+GLI: 5.1±0.3; HFD+t-AUCB: 5.6±0.2 mmol/L; p<0.05). However, only t-AUCB improved glucose tolerance and decreased gluconeogenesis. In parallel, t-AUCB prevented adipose tissue activation and dyslipidemia. Moreover, t-AUCB improved coronary endothelial function and prevented diastolic dysfunction, as shown by echocardiography (E/A ratio; Control: 1.25±0.02; HFD: 1.05±0.03; HFD+GLI: 1.07±0.04; HFD+t-AUCB: 1.23±0.04; p<0.05) and invasive hemodynamics (LVEDPVR; Control: 1.9±0.55; HFD: 3.8±0.61; HFD+GLI: 3.1±0.8; HFD+t- AUCB: 1.88±0.2 mmHg/RVU; p<0.05). Finally, t-AUCB prevented the increased urinary albumine-to-creatinine ratio and decreased renal inflammation. Discussion These results demonstrate that beyond its glucose-lowering effects sEH inhibition improves coronary endothelial function, diastolic dysfunction and prevents early kidney damage in a murine model of type 2 diabetes. This positive impact on target organ damage and metabolic homeostasis prompts sEH inhibition as a promising therapeutic perspective in type 2 diabetes.
    Archives of Cardiovascular Diseases Supplements 04/2014; 6:14.
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    ABSTRACT: Introduction: Cardiovascular diseases are a leading cause of death in developed countries. Increasing evidence shows that the alteration in the normal functions of the vascular endothelium plays a major role in the development of cardiovascular diseases. However, specific agents designed to prevent endothelial dysfunction and related cardiovascular complications are still lacking. One emerging strategy is to increase the bioavailability of epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases from arachidonic acid. EETs are endothelium-derived hyperpolarising and relaxing factors and display attractive anti-inflammatory and metabolic properties. Genetic polymorphism studies in humans, and experiments in animal models of diseases, have identified soluble epoxide hydrolase (sEH), the major enzyme involved in EET degradation, as a potential pharmacological target. Areas covered: This review presents EET pathway and its functions and summarises the data supporting the development of sEH inhibitors for the treatment of cardiovascular and metabolic diseases. Furthermore, the authors present the different chemical families of sEH inhibitors developed and their effects in animal models of cardiovascular and metabolic diseases. Expert opinion: Several generations of sEH inhibitors have now been designed to treat endothelial dysfunction and cardiovascular complications for a variety of diseases. The safety of these drugs remains to be carefully investigated, particularly in relation to carcinogenesis. The increasing knowledge of the biological role of each of the EET isomers and of their metabolites may improve their pharmacological profile. This, in turn, could potentially lead to the identification of new pharmacological agents that achieve the cellular effects needed without the deleterious side effects.
    Expert Opinion on Drug Discovery 02/2014; · 2.30 Impact Factor
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    ABSTRACT: Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.
    La Revue de Médecine Interne 01/2014; · 0.90 Impact Factor
  • Dominique Guerrot, Jeremy Bellien
    Cardiovascular & Haematological Disorders - Drug Targets(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders) 01/2014; 14(1).
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    ABSTRACT: Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.
    La Revue de Médecine Interne. 01/2014;
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    ABSTRACT: Middle molecular weight uraemic toxins are considered to play an important role in vascular dysfunction and cardiovascular outcomes in end-stage renal disease (ESRD) patients. Recent dialysis techniques based on convection, specifically high-efficiency on-line haemodiafiltration (HDF), enhance the removal of middle molecular weight toxins and reduce all-cause mortality in haemodialysis (HD) patients. However, the mechanisms of these improved outcomes remain to be established. This prospective study randomly assigned 42 ESRD patients to switch from high-flux HD to high-efficiency on-line HDF (n = 22) or to continue HD (n = 20). Brachial artery endothelium-dependent flow-mediated dilatation, central pulse pressure, carotid artery intima-media thickness (IMT), internal diastolic diameter and distensibility and circulating markers of uraemia, inflammation and oxidative stress were blindly assessed before and after a 4-month follow-up. Brachial flow-mediated dilatation and carotid artery distensibility increased significantly in the HDF group compared with HD, while carotid IMT and diameter remained similar. HDF decreased predialysis levels of the uraemic toxins β2-microglobulin, phosphate and blood TNFα mRNA expression. Oxidative stress markers were not different between the HD and HDF groups. Blood mRNA expression of protein kinase C β2, an endothelial NO-synthase (eNOS) inhibitor, decreased significantly with HDF. High-efficiency on-line HDF prevents the endothelial dysfunction and stiffening of the conduit arteries in ESRD patients compared with high-flux HD. HDF decreases uraemic toxins, vascular inflammation, and is associated with subsequent improvement in eNOS functionality. These results suggest that reduced endothelial dysfunction may be an intermediate mechanism explaining the beneficial outcomes associated with HDF.
    Nephrology Dialysis Transplantation 11/2013; · 3.37 Impact Factor
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    ABSTRACT: AimsCommon carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures.Methods and resultsWe combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)].Conclusion We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.
    European Heart Journal 08/2013; 34(30):2368-80. · 14.72 Impact Factor
  • Artery Research 12/2012; 6(4):144.
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    ABSTRACT: In young healthy subjects, epoxyeicosatrienoic acids synthesized by endothelial cytochrome P450 epoxygenases maintain basal conduit artery diameter during altered NO availability. Whether this compensatory mechanism is effective during essential hypertension is unknown. Radial artery diameter, blood flow, and mean wall shear stress were determined in 14 nontreated essential hypertensive patients and 14 normotensive control subjects during 8 minutes of brachial infusion for inhibitors of cytochrome P450 epoxygenases (fluconazole, 0.4 µmol/min) and NO synthase (N(G)-monomethyl-l-arginine, 8 µmol/min) alone and in combination. In controls, the radial artery diameter was reduced by fluconazole (-0.034 ± 0.012 mm) and N(G)-monomethyl-l-arginine (-0.037 ± 0.010 mm) and to a larger extent by their combination (-0.137 ± 0.011 mm), demonstrating a synergic effect. In contrast, the radial diameter in hypertensive patients was not affected by fluconazole (0.010 ± 0.014 mm) but was reduced by N(G)-monomethyl-l-arginine (-0.091 ± 0.008 mm) to a larger extent than in controls. In parallel, N(G)-monomethyl-l-arginine decreased local plasma nitrite to a lesser extent in hypertensive patients (-14 ± 5 nmol/L) than in controls (-50 ± 10 nmol/L). Moreover, the addition of fluconazole to N(G)-monomethyl-l-arginine did not further decrease radial diameter in patients (-0.086 ± 0.011 mm). Accordingly, fluconazole significantly decreased local epoxyeicosatrienoic acid plasma level in controls (-2.0 ± 0.6 ng/mL) but not in patients (-0.9 ± 0.4 ng/mL). Inhibitors effects on blood flow and endothelium-independent dilatation to sodium nitroprusside were similar between groups. These results show that, in contrast to normotensive subjects, epoxyeicosatrienoic acids did not contribute to the regulation of basal conduit artery diameter and did not compensate for altered NO availability to maintain this diameter in essential hypertensive patients.
    Hypertension 10/2012; · 6.87 Impact Factor
  • Jeremy Bellien, Robinson Joannides
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    ABSTRACT: In response to endothelial cell activation, arachidonic acid can be converted by cytochrome P450 (CYP) epoxygenases to epoxyeicosatrienoic acids (EETs), which have potent vasodilator and anti-inflammatory properties. EETs are rapidly degraded in vivo to the less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). Since the beginning of the 2000's, the role of EET pathway in human health and its alteration in diseases has been shown by measuring EETs/DHET levels in blood, by evaluating the relationship between CYP/sEH gene polymorphisms, which modify enzyme activity and thus EETs/DHET level, and by assessing the inhibitory effect of the local administration of CYP epoxygenase inhibitor on endothelium-dependent dilatation. By combining these functional and biological approaches, we demonstrated that EETs are the endothelial factors released by CYP epoxygenases involved in the flow-mediated dilatation of conduit arteries in healthy subjects, together with the impairment of EET availability in essential hypertensive patients at this level. The modulation of EET pathway now emerges as a new promising pharmacological target that may improve the clinical management of patients at high cardiovascular risk. In this respect, the restoration of EET availability using a new class of agents, the inhibitors of sEH, gave promising results in various animal models of cardiovascular diseases, reducing blood pressure and target organ damage, and a first product has entered clinical evaluation.
    Journal of cardiovascular pharmacology 09/2012; · 2.83 Impact Factor
  • Journal des Maladies Vasculaires 09/2012; 33:S54–S55. · 0.24 Impact Factor
  • Journal des Maladies Vasculaires 09/2012; 37(5):257. · 0.24 Impact Factor
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    ABSTRACT: The incidence of cardiovascular diseases remains high in diabetic patients despite the optimization of blood glucose control and the therapeutic management of risk factors. One emerging promising pharmacological approach that may help to prevent the development of diabetic cardiovascular complications is to improve endothelial function through the restoration of the bioavailability of epoxyeicosatrienoic acids (EETs). EETs are crucial eicosanoid signaling molecules synthesized by cytochrome P450 epoxygenases in the vascular endothelium and in pancreatic islets. EETs promote vasodilatation and display attractive anti-inflammatory and anti-aggregating actions together with potent effects on insulin release and sensitivity. In animal models of insulin-resistance and diabetes, a decrease in EET availability has been reported, and is a deleterious mechanism that probably contributes to multiple metabolic, cardiovascular and renal disorders in this setting. Moreover, increasing experimental evidence suggest that the use of soluble epoxide hydrolase (sEH) inhibitors, which prevent EET degradation, is a promising pharmacological approach to prevent endothelial dysfunction and to protect against target organ damage in metabolic diseases. This review presents evidence that the EET pathway is disturbed from the early stages of metabolic diseases, and analyzes the potential contribution of EETs impairment to the progression of cardiovascular diseases associated with diabetes. Pathophysiological and therapeutic perspectives are thereafter discussed, including the necessity to demonstrate the role of EET pathway alterations in endothelial dysfunction associated with diabetes in human, and the interest of sEH inhibitors to prevent the development of diabetic cardiovascular complications, with the expected result of improving patients' health.
    Cardiovascular & hematological agents in medicinal chemistry 05/2012; 10(3):212-22.
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    ABSTRACT: We sought to clarify, using functional and biological approaches, the role of epoxyeicosatrienoic acids, nitric oxide (NO)/reactive oxygen species balance, and endothelin-1 in conduit artery endothelial dysfunction during essential hypertension. Radial artery diameter and mean wall shear stress were determined in 28 untreated patients with essential hypertension and 30 normotensive control subjects during endothelium-dependent flow-mediated dilatation induced by hand skin heating. The role of epoxyeicosatrienoic acids and NO was assessed with the brachial infusion of inhibitors of cytochrome P450 epoxygenases (fluconazole) and NO synthase (N(G)-monomethyl-l-arginine [L-NMMA]). Compared with controls, hypertensive patients exhibited a decreased flow-mediated dilatation in response to postischemic hyperemia as well as to heating, as shown by the lesser slope of their diameter-shear stress relationship. In controls, heating-induced flow-mediated dilatation was reduced by fluconazole, L-NMMA, and, to a larger extent, by L-NMMA+fluconazole. In patients, flow-mediated dilatation was not affected by fluconazole and was reduced by L-NMMA and L-NMMA+fluconazole to a lesser extent than in controls. Furthermore, local plasma epoxyeicosatrienoic acids increased during heating in controls (an effect diminished by fluconazole) but not in patients. Plasma nitrite, an indicator of NO availability, increased during heating in controls (an effect abolished by L-NMMA) and, to a lesser extent, in patients, whereas, inversely, reactive oxygen species increased more in patients (an effect diminished by L-NMMA). Plasma endothelin-1 decreased during heating in controls but not in patients. These results show that an impaired role of epoxyeicosatrienoic acids contributes, together with an alteration in NO/reactive oxygen species balance and endothelin-1 pathway, to conduit artery endothelial dysfunction in essential hypertension. https://www.eudract.ema.europa.eu. Unique identifier: RCB2007-A001-10-53.
    Circulation 03/2012; 125(10):1266-75. · 15.20 Impact Factor
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    ABSTRACT: The study addressed the hypothesis that soluble epoxide hydrolase (sEH) inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids (EETs), exerts beneficial effects in an established chronic heart failure (CHF) model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after coronary ligation) and delayed 3-day (starting 47 days after coronary ligation) treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 42-day AUDA increased plasma EETs demonstrating the effective inhibition of sEH. Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial pressure, thus reducing total peripheral resistance. Both treatment periods increased the slope of the LV end-systolic pressure-volume relation, but only 42-day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the slope of the LV end-diastolic pressure-volume relation, associated with a reduced LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent, 42-day AUDA increased LV perfusion associated with a decreased LV hypoxia-inducible factor-1alpha. Both treatment periods decreased reactive oxygen species level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, an inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished the beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation of EET availability by pharmacological inhibition of sEH increases LV diastolic and systolic functions in established CHF. This notably results from short-term processes, i.e. increased LV perfusion, reduced LV oxidative stress and peripheral vasodilatation, but also from long-term effects, i.e. reduced LV remodeling.
    Journal of Molecular and Cellular Cardiology 12/2011; 52(3):660-6. · 5.15 Impact Factor
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    ABSTRACT: Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in the CONCEPT trial were randomized at week 12 (W12) to continue CsA or switch to SRL, both associated with mycophenolate mofetil. Carotid systolic blood pressure (cSBP), pulse pressure (cPP), central pressure wave reflection (augmentation index, AIx) and carotid-to-femoral pulse-wave velocity (PWV: aortic stiffness) were blindly assessed at W12, W26 and W52 together with plasma endothelin-1 (ET-1), thiobarbituric acid-reactive substances (TBARS) and superoxide dismutase (SOD) and catalase erythrocyte activities. At W12, there was no difference between groups. At follow-up, PWV, cSBP, cPP and AIx were lower in the SRL group. The difference in PWV remained significant after adjustment for blood pressure and eGFR. In parallel, ET-1 decreased in the SRL group, while TBARS, SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group. Our results demonstrate that a CsA-free regimen based on SRL reduces aortic stiffness, plasma endothelin-1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction.
    American Journal of Transplantation 09/2011; 11(11):2414-22. · 6.19 Impact Factor
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    ABSTRACT: Progress in methods of investigating endothelial function in humans has led to the demonstration that endothelial dysfunction is an early process involved in the pathophysiology of cardiovascular diseases, and represents a new independent therapeutic target that may help to improve patient health. The administration of antioxidant, anti-hypertensive, lipid lowering or antidiabetic agents appear insufficient to fully restore the normal functions of the vascular endothelium and specific therapeutic strategies are still lacking. In this context, one emerging promising pharmacological approach to prevent endothelial dysfunction is to restore epoxyeicosatrienoic acids (EETs) pathway. EETs are eicosanoids synthesized by endothelial cytochrome epoxygenases that contribute to the regulation of endothelium-dependent dilatation, vascular inflammation, cell proliferation, angiogenesis and hemostasis. Moreover, it has been shown in vivo in humans that EETs act as endothelium-derived hyperpolarizing factors to regulate the vascular tone in both resistance and conduit arteries. In various cardiovascular disorders such as arterial hypertension, a decrease in EETs availability, due to an increased degradation by soluble epoxide hydrolase (sEH), is a deleterious mechanism that contributes to endothelial dysfunction and promotes cardiovascular inflammation and remodeling. Subsequently, the use of sEH inhibitors, which have been shown to decrease blood pressure, limit ischemic injury and prevent hypertrophy in various animal models, appears to be an attractive opportunity to restore endothelial function. Future research will be necessary to demonstrate that sEH inhibitors can prevent endothelial dysfunction in human arteries, which may help to prevent the development of cardiovascular complications and improve cardiovascular prognosis in patients.
    Pharmacology [?] Therapeutics 07/2011; 131(1):1-17. · 7.79 Impact Factor
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    ABSTRACT: The purpose of this study was to correlate the arterial mechanics of carotid atherosclerotic plaques assessed from echotracking with their composition by high-resolution magnetic resonance imaging (HR-MRI). Analysis of the relationship between mechanical parameters and structure of the plaque allows better understanding of the mechanisms leading to mechanical fatigue of plaque material, plaque rupture, and ischemic events. A specific longitudinal gradient of strain (reduced strain, i.e., lower radial strain at the plaque level than at the adjacent segment) has been shown in atherosclerotic plaques on the common carotid artery (CCA) in patients with hypertension, dyslipidemia, or type 2 diabetes mellitus. The structural abnormalities underlying this functional behavior have not been determined. Forty-six carotid plaques from 27 patients were evaluated; plaques were present at the site of the carotid bifurcation and extended to the CCA. Among the 27 patients, 9 had previous ischemic stroke ipsilateral to carotid stenosis (symptomatic) and 18 had not (asymptomatic). Mechanical parameters were measured at 128 sites on a 4-cm long CCA segment by noninvasive echotracking system, and strain gradient was calculated. Plaque composition was noninvasively determined by HR-MRI. Complex plaques at HR-MRI (i.e., American Heart Association [AHA] stages IV to VIII) more often displayed a reduced strain than the simple plaques (i.e., AHA stages I to III; p = 0.046). HR-MRI verified complex plaques were associated with an outer remodeling upon echotracking, and had a lower distensibility than adjacent CCA (17.0 ± 5.0 MPa⁻¹ vs. 21.7 ± 7.3 MPa⁻¹; p = 0.007). An outer remodeling was observed in plaques with a lipid core at HR-MRI and was more frequent in symptomatic carotids. These findings indicate that the longitudinal mechanics of "complex" plaques follows a specific pattern of reduced strain. They also suggest that reduced strain, associated with an outer remodeling, may be a feature of high-risk plaques.
    JACC. Cardiovascular imaging 05/2011; 4(5):468-77. · 14.29 Impact Factor

Publication Stats

274 Citations
145.24 Total Impact Points

Institutions

  • 2005–2013
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
  • 2012
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2006–2012
    • French Institute of Health and Medical Research
      • Institut Mondor de Recherche Biomédicale (IMRB) U955
      Lutetia Parisorum, Île-de-France, France
  • 2008–2010
    • Université de Rouen
      Mont-Saint-Aignan, Upper Normandy, France