CLEC-2 is required for the activation of mouse platelets by bacterial DNA mimetics
Delierneux, Céline ; Hego, Alexandre ; LECUT, Christelle et al
Conference (2015, June 22)
Aims: To evaluate whether CpG ODNs affect platelet activation and thrombus formation via CLEC-2 and TLR9. Methods: We incubated washed platelets or whole blood from TLR9-, MyD88- or CLEC-2- deficient mice ... [more ▼]
Aims: To evaluate whether CpG ODNs affect platelet activation and thrombus formation via CLEC-2 and TLR9. Methods: We incubated washed platelets or whole blood from TLR9-, MyD88- or CLEC-2- deficient mice with CpG ODNs. We performed platelet aggregometry, flow cytometric binding and platelet activation assays as well as signal transduction analyses. Thrombus formation and fibrin generation were also analyzed by intravital microscopy in mouse microcirculation upon intravenous injection of CpG ODNs. Results: We show that CpG ODNs bind on platelet surface and are internalized. They activate platelets and induce their aggregation. TLR9- or MyD88-deficient platelets aggregated normally in response to CpG ODN. Interestingly, platelets deficient for the C-type lectin receptor CLEC-2 were unable to capture and internalize CpG ODN. CLEC-2 deficiency abolished CpG ODN-induced platelet activation and aggregation. CpG ODN stimulated CLEC-2 dependent tyrosine kinase pathway and Syk phosphorylation. In vivo, intravenously injected CpG ODN interacted with platelets adhered to laser injured arteriolar endothelia and promoted fibrin generation and thrombus growth. Conclusion: CLEC-2 mediates CpG ODN uptake and subsequent platelet activation, independently of TLR9, which may serve an important role in the interplay between platelets and immunity. [less ▲]Detailed reference viewed: 22 (1 ULg)
High-dose oral intake of serotonin induces valvular heart disease in rabbits.
Lancellotti, Patrizio ; NCHIMI LONGANG, Alain ; Hego, Alexandre et al
in International Journal of Cardiology (2015), 197
Carcinoid tumors are rare neuroendocrine malignancies, often originating from enterochromaffin cells in the gastrointestinal tract. They can secrete serotonin (5-hydroxytryptamine, 5-HT), which is largely ... [more ▼]
Carcinoid tumors are rare neuroendocrine malignancies, often originating from enterochromaffin cells in the gastrointestinal tract. They can secrete serotonin (5-hydroxytryptamine, 5-HT), which is largely inactivated by the liver. Carcinoid heart disease occurs when tumor cells metastasize to the liver, as the vasoactive substances produced are able to reach the systemic circulation via the hepatic vein, causing deposition of fibrous tissue on the endocardial surfaces of the heart. It is predominantly manifested by right-sided valvular heart disease (VHD). Scavenging enzymes in the pulmonary endothelium may explain why left-sided cardiac involvement is unusual. The severity of cardiac damage is correlated with the plasmatic levels of serotonin, but the lowspecificity of serotonin for cardiac damage suggests that serotonin may be necessary but not sufficient to induce cardiac lesions. Therefore, other factors combined with serotonin might be required to induce VHD. However, recent animal studies confirmed the development of carcinoid-like valvular deposits in rats after 3 months of daily subcutaneous/intraperitoneal serotonin injections to avoid the liver first-pass clearance.Whether oral administration of serotonin can also induce VHD is unknown. We hypothesized that long-term oral serotonin overload in rabbits can lead to VHD, mimicking serotonin-induced lesions of carcinoid heart disease. We demonstrate, for the first time that high dose long-term oral administration of serotonin can lead to VHD in rabbits. [less ▲]Detailed reference viewed: 42 (3 ULg)
Prise en charge de l'IM dystrophique: nouveaux indices pronostiques
; LANCELLOTTI, Patrizio
in Réalités Cardiologiques (2015)Detailed reference viewed: 19 (0 ULg)
STENOSE AORTIQUE SEVERE ASYMPTOMATIQUE A FRACTION D'EJECTION VENTRICULAIRE GAUCHE PRESERVEE. EVALUATION A L'EFFORT: QUELS RESULTATS ET QUELLES DECISIONS?
; ; et al
in Annales de Cardiologie et d'Angeiologie (2015), 64(2), 100-108Detailed reference viewed: 32 (4 ULg)
DUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ; ; et al
in Circulation (2015), 131(7), 656-68
Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]
Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]Detailed reference viewed: 128 (55 ULg)
La cardiomyopathie du cirrhotique : un bref aperçu
MARCHETTA, Stella ; DELWAIDE, Jean ; LANCELLOTTI, Patrizio
in Revue Médicale de Liège (2015), 2Detailed reference viewed: 61 (4 ULg)
Bacterial DNA mimetics activate platelets and promote thrombosis via CLEC-2
; ; et al
Poster (2015, January 27)Detailed reference viewed: 16 (0 ULg)
Exercice stress echocardiography in secondary mitral regurgitation : impact of pulmonary hypertension
; PIERARD, Luc ; LANCELLOTTI, Patrizio
in Archives of Cardiovascular Diseases (2015, January), 7Detailed reference viewed: 4 (0 ULg)
Prevention of ventilator-associated pneumonia and ventilator-associated conditions: A randomized controlled trial with subglottic secretion suctioning
DAMAS, Pierre ; FRIPPIAT, Frédéric ; ANCION, Arnaud et al
in Critical Care Medicine (2015), 43(1), 22-30Detailed reference viewed: 89 (37 ULg)
Positron Emission Tomography/Computed Tomography Imaging in Device Infective Endocarditis: Ready for Prime Time
Lancellotti, Patrizio ; ; Oury, Cécile et al
in Circulation (2015), 132
Over the last decade there has been a remarkable increase in prosthetic heart valve replacement and cardiac implantable electronic device utilization. Although capable of improving the quality and ... [more ▼]
Over the last decade there has been a remarkable increase in prosthetic heart valve replacement and cardiac implantable electronic device utilization. Although capable of improving the quality and quantity of life of patients suffering from severe valvular heart disease or rhythm disorders, they are both subject to potentially life-threatening infection involving the endocardium, referred to as device infective endocarditis (DIE)1,2. The rate of prosthetic valve endocarditis (PVE) ranges from 1-6% to 15%, being higher in revision surgery1. The infection usually involves the junction between the sewing ring and the annulus, leading to perivalvular abscess, dehiscence, pseudo-aneurysms, and fistulae, or the leaflets of the prosthesis, leading to vegetations, cusp rupture, and perforation. Cardiac device-related infective endocarditis (CDRIE), to be distinguished from local device infection (pocket/generator), is defined as an infection involving the electrode leads, cardiac valve leaflets, or endocardial surface. An incidence of 1.4 per 1000 device-years of definite CDRIE has been reported3. DIE may occur at anytime, being related to surgery only in early cases. [less ▲]Detailed reference viewed: 47 (24 ULg)
2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC)Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM).
; LANCELLOTTI, Patrizio ; et al
in European heart journal (2015), 36(44), 3075-128Detailed reference viewed: 20 (2 ULg)
2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS).
; ; et al
in European heart journal (2015), 36(42), 2921-64Detailed reference viewed: 30 (0 ULg)
Elevated Plasma Soluble ST2 Is Associated with Heart Failure Symptoms and Outcome in Aortic Stenosis.
LANCELLOTTI, Patrizio ; DULGHERU, Raluca Elena ; et al
in PloS one (2015), 10(9), 0138940
B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is ... [more ▼]
B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74+/-13 years; 59 asymptomatic, 69%) with AS (<1.5 cm2) and preserved left ventricular ejection fraction who were followed-up for 26+/-16 months. Both BNP and sST2 were associated with NYHA class but sST2 (>23 ng/mL, AUC = 0.68, p<0.01) was more accurate to identify asymptomatic patients or those who developed symptoms during follow-up. sST2 was independently related to left atrial index (p<0.0001) and aortic valve area (p = 0.004; model R2 = 0.32). A modest correlation was found with BNP (r = 0.4, p<0.01). During follow-up, 29 asymptomatic patients (34%) developed heart failure symptoms. With multivariable analysis, peak aortic jet velocity (HR = 2.7, p = 0.007) and sST2 level (HR = 1.04, p = 0.03) were independent predictors of cardiovascular events. In AS, sST2 levels could provide complementary information regarding symptomatic status, new onset heart failure symptoms and outcome. It might become a promising biomarker in these patients. [less ▲]Detailed reference viewed: 35 (7 ULg)
New biomarkers for primary mitral regurgitation.
Deroyer, Céline ; ; Moonen, Marie et al
in Clinical proteomics (2015), 12
BACKGROUND: Mitral regurgitation is a frequent valvular heart disease affecting around 2.5 % of the population with prevalence directly related to aging. Degeneration of mitral valve is broadly considered ... [more ▼]
BACKGROUND: Mitral regurgitation is a frequent valvular heart disease affecting around 2.5 % of the population with prevalence directly related to aging. Degeneration of mitral valve is broadly considered as a passive ongoing pathophysiological process and little is known about its physiological deregulation. The purpose of this study was to highlight new biomarkers of mitral regurgitation in order to decipher the underlying pathological mechanism as well as to allow the diagnosis and the monitoring of the disease. RESULTS: Modulation of various blood proteins expression was examined in patients suffering from different grades of mitral regurgitation (mild, moderate and severe) compared to healthy controls. To this end, several routine clinical assays and the multi analyte profile technology targeting 184 proteins were used. High-density lipoprotein, apolipoprotein-A1, haptoglobin and haptoglobin-alpha2 chain levels significantly decreased proportionally to the degree of mitral regurgitation when compared to controls. High-density lipoprotein and apolipoprotein-A1 levels were associated with effective regurgitant orifice area and regurgitant volume. Apolipoprotein-A1 was an independent predictor of severe mitral regurgitation. Moreover, with ordinal logistic regression, apolipoprotein-A1 remained the only independent factor associated with mitral regurgitation. In addition, myxomatous mitral valves were studied by immunocytochemistry. We observed an increase of LC3, the marker of autophagy, in myxomatous mitral valves compared with healthy mitral valves. CONCLUSION: These potential biomarkers of mitral regurgitation highlighted different cellular processes that could be modified in myxomatous degenerescence: reverse cholesterol transport, antioxidant properties and autophagy. [less ▲]Detailed reference viewed: 67 (16 ULg)
2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
; ; et al
in European heart journal (2015), 36(41), 2793-867Detailed reference viewed: 25 (0 ULg)
Cardiovascular outcome in systemic sclerosis.
; ; DULGHERU, Raluca Elena et al
in Acta cardiologica (2015), 70(5), 554-63
OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC ... [more ▼]
OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc. METHODS: We prospectively enrolled 65 patients with SSc (age 54+/-14 years, 30% female) followed in CHU Sart-Tilman, Liege, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise. RESULTS: EIPH was present in 21 patients. During FU (27+/-18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63+/-14 vs 52+/-13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30+/-6 vs 24+/-6; P=0.007 and 57+/-13 vs 44+/-13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112+/-106 vs 26+/-19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ss=2.4+/-1.1; P=0.03), EIPH (ss=2.30+/-1.13; P=0.04), FUPH (ss=0.24+/-0.09; P=0.01 and ss=3.52+/-1.16; P=0.002, respectively;) and BNP (ss=0.08+/-0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001). CONCLUSION: Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc. [less ▲]Detailed reference viewed: 25 (1 ULg)
Biological Effects of Cardiac Magnetic Resonance on Human Blood Cells.
LANCELLOTTI, Patrizio ; NCHIMI LONGANG, Alain ; Delierneux, Céline et al
in Circulation. Cardiovascular imaging (2015), 8(9),
BACKGROUND: Cardiac magnetic resonance (CMR) is increasingly used for the diagnosis and management of cardiac diseases. Recent studies have reported immediate post-CMR DNA double-strand breaks in T ... [more ▼]
BACKGROUND: Cardiac magnetic resonance (CMR) is increasingly used for the diagnosis and management of cardiac diseases. Recent studies have reported immediate post-CMR DNA double-strand breaks in T lymphocytes. We sought to evaluate CMR-induced DNA damage in lymphocytes, alterations of blood cells, and their temporal persistence. METHODS AND RESULTS: In 20 prospectively enrolled healthy men (31.4+/-7.9 years), blood was drawn before and after (1-2 hours, 2 days, 1 month, and 1 year) unenhanced 1.5T CMR. Blood cell counts, cell death, and activation status of lymphocytes, monocytes, neutrophils, and platelets were evaluated. The first 2-hour post-CMR were characterized by a small increase of lymphocyte B and neutrophil counts and a transient drop of total lymphocytes because of a decrease in natural killer cells. Among blood cells, only neutrophils and monocytes displayed slight and transient activation. DNA double-strand breaks in lymphocytes were quantified through flow cytometric analysis of H2AX phosphorylation (gamma-H2AX). gamma-H2AX intensity in T lymphocytes did not change early after CMR but increased significantly at day 2 </=1 month before returning to baseline levels of 1-year post-CMR. CONCLUSIONS: Unenhanced CMR is associated with minor but significant immediate blood cell alterations or activations figuring inflammatory response, as well as DNA damage in T lymphocytes observed from day 2 until the first month but disappearing at 1-year follow-up. Although further studies are required to definitely state whether CMR can be used safely, our findings already call for caution when it comes to repeat this examination within a month. [less ▲]Detailed reference viewed: 38 (7 ULg)
2015 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-segment Elevation.
; ; et al
in Revista espanola de cardiologia (English ed.) (2015), 68(12), 1125Detailed reference viewed: 12 (0 ULg)
Young community of EACVI: the transition from EACVI Club 35 to Heart Imagers of Tomorrow: a promising yet challenging step.
; ; et al
in European heart journal cardiovascular Imaging (2015)
The purpose of this review is to summarize the activity and potential of the young community of European Association of Cardiovascular Imaging and to highlight the transition from Club 35 to 'Heart ... [more ▼]
The purpose of this review is to summarize the activity and potential of the young community of European Association of Cardiovascular Imaging and to highlight the transition from Club 35 to 'Heart Imagers of tomorrow'. [less ▲]Detailed reference viewed: 5 (0 ULg)