Philippe Connes

Philippe Connes
Institut Universitaire de France - Claude Bernard University Lyon 1 · LIBM laboratory - Team "Vascular Biology and Red Blood cell"

PhD

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334
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Publications

Publications (334)
Article
It has been long known that blood health heavily influences optimal physiological function. Abnormalities affecting the physical properties of blood have been implicated in the pathogenesis of various disorders, although the exact mechanistic links between hemorheology and clinical disease manifestations remain poorly understood. Often overlooked i...
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Subjects with sickle cell trait (SCT) carry one copy of mutated -globin gene at position E6V at the origin of the production of sickle hemoglobin (HbS). Indeed, individuals with SCT have both normal hemoglobin and HbS, in contrast to patients with sickle cell disease who inherited of two copies of the mutated gene. Although SCT is generally benign...
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Hypoxia is caused by insufficient oxygen availability for the organism leading to reduced oxygen delivery to tissues and cells. It has been regarded as a severe threat to human health and it is indeed implicated in pathophysiological mechanisms involved in the development and progression of many diseases. Nevertheless, the potential of controlled h...
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Introduction While paramacular retinal atrophy (PRA) is known to be found in 48% of eyes of adults and 42% of eyes of children with homozygous SCD (SS-SCD), the aim of this study is to assess the association between PRA and red blood cell (RBC) deformability, hematological markers and brain imaging abnormalities in SS-SCD. Methods This study is a...
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The aim of this study was to 1) analyze blood viscosity, red blood cell (RBC) deformability and aggregation in hospitalized patients with Coronavirus disease 19 (COVID-19), 2) test the associations between impaired blood rheology and blood coagulation and 3) test the associations between impaired blood rheology and several indicators of clinical se...
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Background: Carotid atherosclerotic plaques remain silent until their rupture, which may lead to detrimental ischemic events such as strokes. This is due, in part, to intraplaque hemorrhages (IPH) and the resulting inflammatory processes, which may promote carotid plaque vulnerability. Currently, the benefits of carotid endarterectomy remain unclea...
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Oxygen gradient ektacytometry (oxygenscan) measures the changes in red blood cell (RBC) deformability in normoxia and during deoxygenation. We investigated the changes in RBC deformability measured by both the oxygenscan and the classical shear stress gradient ektacytometry in 10 patients with sickle cell disease (SCD) during vaso-occlusive crisis...
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Purpose Sickle cell trait is characterized by the presence of both normal and abnormal haemoglobin in red blood cells. The rate of exertional collapse is increased in athletes and military recruits who carry the trait, particularly in stressful environmental conditions. The aim of the present study was to investigate microvascular function and its...
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Red blood cells in sickle cell anemia (sRBC) are more heterogeneous in their physical properties than healthy red blood cells, spanning adhesiveness, rigidity, density, size, and shape. sRBC with increased adhesiveness to the vascular wall would trigger vaso-occlusive like complications, a hallmark of sickle cell anemia. We investigated whether seg...
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Les globules rouges (GR) peuvent servir de transporteurs d’agents thérapeutiques afin d’améliorer leur pharmacocinétique et leur pharmacodynamique. Afin d’évaluer l’impact de la plateforme ERYCAPS® (encapsulation par dialyse hypotonique) sur la physiologie des GR, plusieurs paramètres ont été comparés entre eryaspase (asparaginase encapsulée dans l...
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Red blood cell (RBC) exchanges (RCE) are frequently used to treat and prevent cerebrovascular complications in patients with sickle cell anemia (SCA). However, the low weight of young children represents serious concerns for this procedure. The Spectra Optia device can perform automatic priming using RBCs (RCE/RBC-primed) which could allow RCE to b...
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Red blood cells (RBCs) can act as carriers for therapeutic agents and can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier. We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and...
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Purpose: Sickle cell disease (SCD) patients exhibit a limited exercise tolerance commonly attributed to anaemia, as well as hemorheological and cardio-respiratory abnormalities, but the functional status of skeletal muscle at exercise is unknown. Moreover, the effect of SCD genotype on exercise tolerance and skeletal muscle function has been poorly...
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Background: Although obstructive sleep apnea (OSA) could act as a modulator of clinical severity in sickle cell disease (SCD), few studies focused on the associations between the two diseases. Research Question: The aims of this study were: (1) to explore the associations between OSA, nocturnal oxyhemoglobin saturation (SpO2) and the history of sev...
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This study tested the impact of alpha-thalassemia on oxygen gradient ektacytometry in sickle cell anemia (SCA). Three SCA groups were compared: 1) no alpha-thalassaemia (4 alpha-genes; n=62), 2) silent alpha-thalassaemia (3 alpha-genes; n=35) and 3) homozygous alpha-thalassaemia (2 alpha-genes; n=12). RBC deformability measured in normoxia was not...
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Prototype of monogenic disorder, sickle cell disease (SCD) is caused by a unique single mutation in the β-globin gene, leading to the production of the abnormal hemoglobin S (HbS). HbS polymerization in deoxygenated condition induces the sickling of red blood cells (RBCs), which become less deformable and more fragile, and thus prone to lysis. In a...
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Patients with sickle cell disease (SCD) have reduced functional capacity due to anemia and cardio-respiratory abnormalities. Recent studies also suggest the presence of muscle dysfunction. However, the interaction between exercise capacity and muscle function is currently unknown in SCD. The aim of this study was to explore how muscle dysfunction m...
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This study aimed to investigate the changes in blood viscosity, pulmonary hemodynamics, NO production and maximal oxygen uptake (V̇O2max) during a maximal incremental test conducted in normoxia and during exposure to moderate altitude (2400m) in athletes exhibiting exercise-induced hypoxemia at sea level (EIH). Nine endurance athletes with EIH and...
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Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis and the presence of erythrocytes with low deformability, which may trigger vaso-occlusive crises. We tested the in-vitro effects of aqueous extract of Chives (Allium schoenoprasum L.) on erythrocyte deformability of SCA patients. Blood samples from 6 apparently health...
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Despite its high prevalence in children with sickle cell anemia (SCA), the pathophysiology of silent cerebral infarcts (SCIs) remains elusive. The main objective of this study was to explore the respective roles of major determinants of brain perfusion in SCA children with no past or current history of intracranial or extracranial vasculopathy. We...
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(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC and S/b+) or under different treatment (hydroxyurea or chronic red blood cell exchange); (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady-state....
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Inflammation and oxidative stress play a key role in the pathophysiology of sickle cell disease (SCD). However, the potential influence of different sickle genotypes, or hydroxyurea (HU) treatment on these factors remains poorly documented. The present study compared several plasma markers of inflammation and oxidative stress, as well as microvascu...
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BACKGROUND: Endurance running events are known to cause inflammation and result in increased cytokine production. However, the effects of ultramarathons on cytokine profiles are not well characterized. OBJECTIVE: The aim of this study was to describe and compare the effects of a trail (40 km) race and an ultra-trail (171 km) race on leukocyte conc...
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(1) Background: It is known that sickle cells contain a higher amount of Ca2+ compared to healthy red blood cells (RBCs). The increased Ca2+ is associated with the most severe symptom of sickle cell disease (SCD), the vaso-occlusive crisis (VOC). The Ca2+ entry pathway received the name of Psickle but its molecular identity remains only partly reso...
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Here we describe the effects of a controlled, 30-minute, high-intensity cycling test on blood rheology and metabolic profiles of red blood cells (RBC) from well-trained males. RBC demonstrated decreased deformability and trended towards increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidati...
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Sickle cell disease (SCD) is a hereditary disorder that leads to the production of an abnormal hemoglobin, hemoglobin S (HbS). HbS polymerizes in deoxygenated conditions, which can prompt red blood cell (RBC) sickling and leaves the RBCs more rigid, fragile and prone to hemolysis. SCD patients suffer from a plethora of complications, ranging from a...
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Purpose: To identify genetic, systemic and biological factors associated with the occurrence of sickle cell maculopathy (SCM). To evaluate microvascular macular alterations using optical coherence tomography angiography (OCTA) in sickle cell disease (SCD). Design: Cross-sectional study. Methods: One hundred fifty-one eyes of 78 adult SCD patients (...
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Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a functio...
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Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological and red blood cell (RBC) senescence parameters. Eleven runners participated in a 40 km race (MCC, elevation gain: 2,300 m) and 12 others in the Ultra-Trail du Mont Blanc...
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Background: In sickle cell disease (SCD), hemoglobin S (HbS) polymerizes upon deoxygenation, reducing red blood cell (RBC) deformability. RBC deformability can be measured over a gradient of oxygen tensions (pO2) with the Laser Optical Rotational Red Cell Analyzer (Lorrca) ektacytometer (RR Mechatronics). Oxygen gradient ektacytometry generates 3 k...
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Chronic hemolysis, enhanced oxidative stress and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs), however their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains...
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Sickle cell anemia (SCA) is a disease characterized by abnormal red blood cell rheology. Because of their effects on HbS polymerization and red blood cell deformability, alpha-thalassemia and the residual HbF level are known genetic modifiers of the disease. The aim of our study was to determine if the number of HbF quantitative trait loci (QTL) wo...
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Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs233322) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD,...
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Little is known about hemostasis modifications induced by chronic hypoxic exposure in high-altitude residents, especially in those who develop excessive erythrocytosis (EE, i.e. hemoglobin concentration ≥ 21 g·dL-1 in male and ≥ 19 g·dL-1 in female). The aim of this preliminary study was to assess coagulation alterations in highlanders with or with...
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Background: Blood transfusion is the cornerstone treatment to reduce the clinical severity of sickle cell disease (SCD), but we need to maintain the hematocrit (Hct) within an acceptable range to avoid a deleterious increase in blood viscosity. The aim of this study was to compare the effects of manual versus automated red blood cell (RBC) Exchang...
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Background: Cardiovascular diseases remain as the leading cause of morbidity and mortality in industrialized countries. Ageing and gender strongly modulate the risk to develop cardiovascular diseases but very few studies have investigated the impact of gender on cardiovascular diseases in the elderly, which represents a growing population. The pur...
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Key points: Highlanders developed unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. A significant proportion of populations living permanently at high altitude developed however maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects...
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Despite the fact that Red Blood Cells (RBCs) have been intensively studied in the past 50 years to characterize mechanical phenotypes associated with both healthy and pathological states, only ektacytometry (i.e., laser diffractometry) is currently used by hematologists to screen for RBC membrane disorders. Therefore, the development of new diagnos...
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Background: Platelet activation is associated with abdominal obesity and exercise training is an important modulator of body weight. Objective: We investigated the effects of two high intensity interval exercise (HIIE) protocols of different intensity and duration on platelet indices and platelet aggregation in overweight men. Methods: Ten ove...
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Microparticles (MPs) are submicron extracellular vesicles exposing phosphatidylserine (PS) detected in large quantities in the circulation of sickle cell anemia (SS) patients. Several groups studied the biological effects of MPs generated ex vivo. Here, we analyzed for the first time the impact of circulating MPs of 60 sickle cell disease (SCD) pat...
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Full-text available
Sickle cell disease (SCD) is a genetic disease caused by a single mutation in the b-globin gene, leading to the production of an abnormal hemoglobin called hemoglobin S (HbS), which polymerizes under deoxygenation, and induces the sickling of red blood cells (RBCs). Sickled RBCs are very fragile and rigid, and patients consequently become anemic an...
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Full-text available
Perceived exertion is an important self-limiting factor influencing functional capacity in patients with sickle cell anemia (SCA). Exercise-related hemoglobin desaturation (EHD) may occur during a six-minute walking test (6MWT) and could influence the perceived rate of exertion. The aims of this study were (1) to compare the 6MWT responses (heart r...
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Purpose: Blood rheology is a key determinant of blood flow and tissue perfusion. There are still large discrepancies regarding the effects of an acute running exercise on blood rheological properties and red blood cell (RBC) physiology. We investigated the effect of a 10km running trial on markers of blood rheology and RBC physiology in endurance t...
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Patients with sickle cell anemia (SCA) show impaired ventilatory efficiency, altered blood rheology, high levels of oxidative/nitrosative stress and enhanced hemolysis with large amounts of circulating free hemoglobin, which reduces nitric oxide (NO) bioavailability. The aim of the study was to investigate whether physical exercise could improve th...
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New findings: What is the central question of this study? What are the effects of repeated subclinical vaso-occlusions on nuclear factor erythroid 2 related factor 2 (Nrf2) and oxidative stress balance regulation in the kidney of transgenic SAD mice? What is the main finding and its importance? In response to hypoxia-reoxygenation, nuclear Nrf2 pr...