Eduardo Anglés-Cano

French Institute of Health and Medical Research (Inserm) - Université Paris Cité, Paris, France · Innovative Therapies in Haemostasis

Thrombus lysis is the consequence of a restricted number of reactions localised to the surface of fibrin. A functional defect or an insufficient fibrinolytic response may lead to thrombosis with severe or fatal clinical consequences, e.g. myocardial infarction and ischemic stroke. Despite this clinical exigency and a real progress in the knowledge...

Background: We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and methods: Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardi...

Accurate sizing of nanoparticles in biological media is important for drug delivery and biomedical imaging applications since size directly influences the nanoparticle processing and nanotoxicity in vivo. Using fluorescence single particle tracking we have succeeded for the first time in following the aggregation of drug delivery nanoparticles in r...

Fibrinolysis and pericellular proteolysis depend on molecular coassembly of plasminogen and its activator on cell, fibrin, or matrix surfaces. We report here the existence of a fibrinolytic cross-talk mechanism bypassing the requirement for their molecular coassembly on the same surface. First, we demonstrate that, despite impaired binding of Glu-p...

Background Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers – i.e., changes over time - in the con...

Background: Elevated concentrations of lipoprotein(a) [Lp(a)] are directly related to an increased risk of cardiovascular diseases, making it a relevant biomarker for clinical risk assessment. However, the lack of global standardization of current Lp(a) measurement procedures (MPs) leads to inconsistent patient care. The International Federation f...

Background: Medical results generated by European CE Marking for In Vitro Diagnostic or in-house tests should be traceable to higher order reference measurement systems (RMS), such as International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-endorsed reference measurement procedures (RMPs) and reference materials. Currently, se...

A number of stressors and inflammatory mediators (cytokines, proteases, oxidative stress mediators) released during inflammation or ischemia stimulate and activate cells in blood, the vessel wall or tissues. The most well-known functional and phenotypic responses of activated cells are (1) the immediate expression and/or release of stored or newly...

Microvesicles (MVs) are key markers in human body fluids that reflect cellular activation related to diseases as thrombosis. These MVs display phosphatidylserine at the outer leaflet of their plasma membrane as specific recognition moieties. The work reported in this manuscript focuses on the development of an original method where MVs are captured...

LIPOPROTEIN(a) : NSFA CONSENSUS Lipoprotein(a), first described in 1963, consists of a low-density lipoprotein (LDL) associated with apolipoprotein(a) [apo(a)] which has a structural similarity with plasminogen but does not have fi-brinolytic activity. This complex structure determines the prothrom¬botic and antifibrinolytic action of high concentr...

Highlights 2022 Eduardo ANGLES-CANO, INSERM-University of Paris. Lipoprotein(a) [Lp(a)] is an apolipoprotein (apo)B100-containing, low-density lipoprotein-like particle rich in cholesterol associated with a second major protein, apolipoprotein (a) [apo(a). Evidence for a causal role of Lp(a) in the pathophysiology of atherosclerotic CVD is now indi...

Background Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (IC...

Lipoprotein(a) is an apolipoprotein B100-containing low-density lipoprotein-like particle that is rich in cholesterol, and is associated with a second major protein, apolipoprotein(a). Apolipoprotein(a) possesses structural similarity to plasminogen but lacks fibrinolytic activity. As a consequence of its composite structure, lipoprotein(a) may: (1...

In our study, CTPA was performed in a population in which we were looking for a cause to clinical deterioration, which might be due to PE, but also to mechanical ventilation-acquired pneumonia. We therefore did not necessarily select a population with a strong suspicion of PE. We did not have a systematic standardized assessment of thromboembolic e...

Purpose: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. Methods: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 b...

Background Coronary artery disease(CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. Objective To de...

A link between periodontitis and atherothrombosis has been highlighted. The aim of this study was to determine the influence of Porphyromonas gingivalis on endothelial microvesicles (EMVPg) shedding and their contribution to endothelial inflammation. Endothelial cells (EC) were infected with P. gingivalis (MOI = 100) for 24 h. EMVPg were isolated a...

The fibrinolytic system plays an important role in breast cancer, favoring progression through extracellular-matrix degradation, angiogenesis, apoptosis and cellular proliferation. The expression of urokinase-type plasminogen activator (uPA) in breast cancer tissue is widely recognized as an unfavorable prognostic factor. However, fibrinolytic acti...

Activation of platelets and neutrophils in septic shock results in the formation of microvascular clots containing an intricate scaffold of fibrin with neutrophil extracellular traps (NETs) DNA. NETs contain multiple components that might impact endogenous fibrinolysis, resulting in failure to lyse clots in the microcirculation and residual systemi...

Background: In healthy subjects fibrinogen γ/γ' circulates at 8-15% of the total plasma fibrinogen concentration. Elevated levels of this variant have been associated with arterial thrombosis, and its diminution with venous thrombosis. The aims of the present work were to analyze the structure of the fibrin network formed on the top of human derma...

Recently, neutrophil extracellular traps (NETs), three-dimensional structures formed of neutrophil enzymes such as neutrophil elastase (NE) and nuclear components (DNA), have been associated with progression in different types of cancer. However, data remain scarce in breast cancer. Thus, the aim of this study was to associate NETs with clinical st...

Background: Atherosclerosis is an inflammatory process involving activation of monocytes recruited by various chemoattractant factors, among which lipoprotein(a) and its specific apolipoprotein apo(a). Lp(a) contains a specific apolipoprotein apo(a) which size is determined by a variable number of repeats of a specific structural domain, the kring...

Abstract: Background: Ischemic heart disease, cerebrovascular accident, and venous thromboembolism have the presence of a thrombotic event in common and represent the most common causes of death within the population. Objective: Since Schiff base copper(II) complexes are able to interact with polyphosphates (PolyP), a procoagulant and potentially p...

Background: Ischemic heart disease, cerebrovascular accident, and venous thromboembolism have the presence of a thrombotic event in common and represent the most common causes of death within the population. Objective: Since Schiff base copper(II) complexes are able to interact with polyphosphates (PolyP), a procoagulant and potentially prothrom...

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms remain unclear but involve a concomitant accumulation of scar tissue together with myofibroblasts activation. Microparticles (MPs) have been investigate...

Background Fibrin provides a temporary matrix at the site of vascular injury. The aims of the present work were (1) to follow fibrin formation and lysis onto the surface of human dermal microvascular endothelial cells (HMEC-1), and (2) to quantify the secretion of fibrinolytic components in the presence of fibrin. Methods Fibrin clots at different...

Renal cell carcinoma (RCC), also called kidney cancer or renal adenocarcinoma, is highly resistant to current treatments. It has been previously reported that a Kunitz-type inhibitor domain-containing protein, isolated from the salivary glands of the Amblyomma cajennense tick, triggers apoptosis in murine renal adenocarcinoma cells (Renca) by inhib...

Introduction: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic-shock...

Table of contents: PHYSICIANS ABSTRACTSO1 Impact of tracheal cuff shape on microaspiration of gastric contents in intubated critically ill patients: a multicenter randomized controlled study (BEST CUFF)Emmanuelle Jaillette, Christophe Girault, Guillaume Brunin, Farid Zerimech, Arnaud Chiche, Céline Broucqsault-Dedrie, Cyril Fayolle, Franck Minacor...

Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clo...

Background: IPF is associated to an important pulmonary vascular and tissular remodeling. Their mechanisms might involve the coagulation cascade through its role on matrix degradation. Microparticules (MP) are key fibrinolytic mediators so far unexplored in IPF. Objectives: To determine plasmatic levels of plasminogen activators (uPA and tPA) and i...

Introduction La fibrose pulmonaire idiopathique (FPI) est associée à un remodelage vasculaire pulmonaire marqué. La fibrinolyse est impliquée dans de nombreux processus de remodelage vasculaire et tissulaire. Ainsi, le but de cette étude est d’étudier le potentiel fibrinolytique du plasma et des microparticules dans le sang circulant de patients at...

Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability=0.68-0.98). However, causal mutations and functional validation of biological pathways modulating Lp(a) metabolism are lacking. We performed a genome-wide association scan to identify genetic variants associate...

Background Plasminogen activation is a ubiquitous source of fibrinolytic and proteolytic activity. Besides its role in prevention of thrombosis, plasminogen is involved in inflammatory reactions in the central nervous system. Plasminogen has been detected in the cerebrospinal fluid (CSF) of patients with inflammatory diseases; however, its origin r...

The invention relates to a method for measuring the plasmine activity of microparticles, in particular circulating microparticles, in a sample of a biological fluid, particularly a biological fluid in a flow situation, wherein said method can be used as a diagnosis method or a method for following a treatment.

Thrombus lysis is the consequence of a restricted number of reactions localized on the surface of fibrin and cell membranes. A functional defect or an insufficient fibrinolytic response may lead to thrombosis with severe or fatal clinical consequences. Despite this clinical need, and real progress

Microvesicles are membrane vesicles shed by activated cells or cells in apoptosis that entrapped in affected tissues are inaccessible by not invasive means. Since microvesicles can be detected in body fluids (blood, tears, saliva, urine), they are considered as messengers of cell suffering. These mobile vectors can generate a wide spectrum of biolo...

Background: Thrombolysis with tissue-type plasminogen activator (t-PA) is the only treatment approved for acute ischemic stroke. Although t-PA is an efficient clot lysis enzyme, it also causes damage to the neurovascular unit, including hemorrhagic transformations and neurotoxicity. Objectives: On the basis of the mechanism of action of t-PA on...

Unlike other serine proteases that are zymogens, the single-chain form of tissue plasminogen activator (sc-tPA) exhibits an intrinsic activity similar to that of its cleaved two-chain form (tc-tPA), especially in the presence of fibrin. In the central nervous system tPA controls brain functions and dysfunctions through its proteolytic activity. We...

Lipoprotein (Lp(a)) and homocysteine (Hcy) are independent risk factors for coronary artery disease (CAD). Hcy promotes the release of free apo(a) from Lp(a). The high fibrin affinity of free apo(a) inhibits plasminogen binding and plasmin generation. Hyperhomocysteinemia can result from a less active variant of methylene tetrahydrofolate reductase...

Thrombin induces CD40 ligand (CD40L) and matrix metalloproteinases (MMPs) under inflammatory/prothrombotic conditions. Thrombin and CD40L could modulate endothelial MMP-10 expression in vitro and in vivo. Human endothelial cells were stimulated with thrombin (0.1-10 U/mL), CD40L (0.25-1 μg/mL), or their combination (thrombin/CD40L) to assess MMP-10...

Tissue-plasminogen activator (tPA) is an ubiquitous and particular serine protease that display low zymogenicity. Indeed, the single-chain form of tPA is as effective as the two-chain form for inducing fibronolysis. Moreover, in the absence of fibrin, the tc-tPA is only five times more active than the sc-tPA. First, tPA was described in the vascula...

Plawinski L, Dejouvencel T, Anglés-Cano E. Fibrinolysis, new concepts: fibrinolytic microvesicles and cross-talk. Thrombus lysis is the consequence of a restricted number of reactions localised to the surface of fibrin. A functional defect or an insufficient fibrinolytic response may lead to thrombosis with severe or fatal clinical consequences, e...

The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammato...

Tissue plasminogen activator (tPA) is an ubiquitous and exceptional serine protease in that it displays low zymogenicity. Indeed, the single-chain tPA (sc-tPA) and two-chain tPA (tc-tPA) display similar activity in the presence of blood templates such as fibrin. Interestingly, tPA was also highlighted in the brain to control neuronal migration, syn...

While extremely relevant to many life science fields, such as biomedical diagnostics and drug delivery, studies on the size of nanoparticulate matter dispersed in biofluids are missing due to a lack of suitable methods. Here we report that fluorescence single particle tracking (fSPT) with maximum entropy analysis is the first technique suited for a...