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1.
Compr Physiol ; 11(2): 1785-1803, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792905

RESUMO

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 acute complications, such as characteristic, frequent, and debilitating vaso-occlusive episodes to chronic organ damage. While RBC sickling is the primary event at the origin of vaso-occlusive processes, other factors that can further increase RBC transit times in the microcirculation may also be required to precipitate vaso-occlusive processes. The adhesion of RBC and leukocytes to activated endothelium and the formation of heterocellular aggregates, as well as increased blood viscosity, are among the mechanisms involved in slowing the progress of RBCs in deoxygenated vascular areas, favoring RBC sickling and promoting vascular occlusion. Chronic inflammatory processes and oxidative stress, which are perpetuated by hemolytic events and ischemia-reperfusion injury, result in this pan cellular activation and some acute events, such as stroke and acute chest syndrome, as well as chronic end-organ damage. Furthermore, impaired vasodilation and vasomotor hyperresponsiveness in SCD also contribute to vaso-occlusive processes. Treating SCD as a vascular disease in addition to its hematological perspective, the present article looks at the interplay between abnormal RBC physiology/integrity, vascular dysfunction and clinical severity in SCD, and discusses existing therapies and novel drugs in development that may ameliorate vascular complications in the disease. © 2021 American Physiological Society. Compr Physiol 11:1785-1803, 2021.

2.
Eur J Haematol ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629431

RESUMO

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 microvascular function, between patients with sickle SC disease (HbSC, n = 19) and patients with sickle cell anemia (HbSS) under hydroxyurea (HU) treatment (n = 16), or not (n = 13). Hemorheological parameters and levels of inflammatory (IL-6, IL-8, IFN-γ, MCP-1, MIP-1ß, TNF-α) and oxidative stress (AOPP, MDA, MPO) markers were determined. Peripheral microcirculatory cutaneous blood flow and immediate microvascular response to local heat were evaluated using laser Doppler flowmetry. Oxidative stress and inflammation were lower in HbSC patients and HbSS patients under HU therapy compared to HbSS patients not treated with HU. Blood viscosity was higher in HbSC than in HbSS patients treated with or not with HU. Vasodilation response of the cutaneous microcirculation to heat stress was higher in HbSS patients receiving HU treatment. Our results clearly established that both sickle cell genotype and HU treatment modulate inflammation and oxidative stress.

4.
Am J Ophthalmol ; 224: 7-17, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412123

RESUMO

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 (43 HbSS, 30 HbSC, 4 S/ß+, and 1 HbS Lepore) and 40 eyes of 20 healthy controls underwent spectral-domain optical coherence tomography (SDOCT) and OCTA using Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). We analyzed the occurrence of SCM, the foveal avascular zone (FAZ) area, and the severity of macular ischemia and studied their relationships with genetic, systemic, and biological parameters using multivariate logistic regression analysis. RESULTS: Maculopathy occurred in 66 eyes (44%), and more frequently in HbSS patients (71%, P = .004). Multivariate analysis identified HbSS genotype and lower prothrombin ratio (PR) as independently associated with SCM (P = .01). Proliferative sickle cell retinopathy was also associated with SCM (P = .02). FAZ enlargement was associated with higher lactate dehydrogenase level (P = .02). Macular ischemia was more severe in patients with lower hemoglobin level (P = .004) and lower PR (P = .01). No flow areas were identified with OCTA even in eyes with no macular thinning (36 eyes, 42%) and appeared more frequently in the temporal superior subfield (36%). CONCLUSIONS: HbSS genotype, abnormal coagulation and hemolysis increase the risk of SCM. OCTA provides valuable criteria to identify potential risk factors of SCM. OCTA also improves detection of early microvascular changes before the onset of macular thinning.

5.
Int J Cancer ; 148(1): 99-105, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930425

RESUMO

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

6.
J Sport Health Sci ; 9(6): 595-603, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33308809

RESUMO

OBJECTIVE: To examine the impact of a 6-week endurance training on red blood cell (RBC) aging and deformability of healthy participants to detect possible improved hemorheological and performance-related adaptations. METHODS: A total of 31 participants (17 females and 14 males) performed a 6-week moderate training protocol (three 1-h running sessions per week at 70% of maximal heart rate). Blood was sampled before and after the training. RBCs from each participant were fractioned according to density and age into 4 RBC subfractions. Subfractions were examined for changes of RBC properties, including aging distribution, RBC deformability, RBC microparticles, and phosphatidylserine concentrations. RBC and plasma nitrite levels were measured as indicators of nitric oxide metabolism. RESULTS: Aerobic performance, peak oxygen consumption, ventilatory thresholds, velocity at the aerobic-anaerobic threshold, and lactate at exhaustion improved after training. The relative amount of both young RBCs and old RBCs increased, and the amount of the main RBC fraction decreased. Phosphatidylserine externalization and RBC-derived microparticles decreased. Overall deformability expressed as shear stress required to achieve half-maximum deformation to theoretical maximal elongation index at infinite shear stress improved in unfractioned RBCs (p < 0.001). Nitrite decreased in total (p = 0.001), young (p < 0.001), main (p < 0.001), and old (p = 0.020) aged RBCs and in plasma (p = 0.002), but not in very old RBCs. CONCLUSION: These results indicate that non-endurance-trained healthy participants benefit from a regular moderate running training program because performance-related parameters improve and a younger RBC population with improved RBC properties is induced, which might support oxygen supply in the microcirculation.

7.
Br J Haematol ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33249569

RESUMO

Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the natural history of the disease on this continent remains largely unknown. Intravascular haemolysis results in activation of circulating blood cells and release of microparticles (MPs) that exert pro-inflammatory effects and contribute to vascular damage. We designed a case-control study nested in the CADRE cohort (Coeur-Artère-DRÉpanocytose, clinical trials.gov identifier NCTO3114137) and based on extreme phenotypes, to analyse blood cell-derived MPs in 232 adult SS patients at steady state in Bamako and Dakar. Thirty-six healthy adult controls matched by age and sex were recruited in Bamako. The MPs concentrations were higher in SS patients compared to AA controls with a predominance of erythrocyte- and reticulocyte-derived MPs. These erythroid-derived MPs were significantly lower in patients with retinopathy (P = 0·022). Reticulocyte-derived MPs were significantly negatively and positively associated with a history of priapism (P = 0·020) and leg ulcers (P = 0·041) respectively. We describe for the first time the comparative patterns of plasma MPs in healthy subjects and patients with SCD living in sub-Saharan Africa and exhibiting various complications. Because our present results show no clear pattern of correlation between erythroid MPs and the classical hyper-haemolytic complications, we hypothesise a weak relevance of the hyper-haemolysis versus hyper-viscous paradigm in Africa.

8.
Front Immunol ; 11: 551441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250889

RESUMO

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 poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals. In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.

9.
Blood ; 136(2): 247-256, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32285120

RESUMO

Microparticles (MPs) are submicron extracellular vesicles exposing phosphatidylserine (PS), detected at high concentration 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 on endothelial cells (ECs) from 60 sickle cell disease (SCD) patients. MPs were collected from SCD patients and compared with MPs isolated from healthy individuals (AA). Other plasma MPs were purified from SS patients before and 2 years after the onset of hydroxyurea (HU) treatment or during a vaso-occlusive crisis and at steady-state. Compared with AA MPs, SS MPs increased EC ICAM-1 messenger RNA and protein levels, as well as neutrophil adhesion. We showed that ICAM-1 overexpression was primarily caused by MPs derived from erythrocytes, rather than from platelets, and that it was abolished by MP PS capping using annexin V. MPs from SS patients treated with HU were less efficient to induce a proinflammatory phenotype in ECs compared with MPs collected before therapy. In contrast, MPs released during crisis increased ICAM-1 and neutrophil adhesion levels, in a PS-dependent manner, compared with MPs collected at steady-state. Furthermore, neutrophil adhesion was abolished by a blocking anti-ICAM-1 antibody. Our study provides evidence that MPs play a key role in SCD pathophysiology by triggering a proinflammatory phenotype of ECs. We also uncover a new mode of action for HU and identify potential therapeutics: annexin V and anti-ICAM-1 antibodies.

10.
Front Immunol ; 11: 454, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231672

RESUMO

Sickle cell disease (SCD) is a genetic disease caused by a single mutation in the ß-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 and develop frequent and recurrent vaso-occlusive crises. However, it is now evident that SCD is not only a RBC rheological disease. Accumulating evidence shows that SCD is also characterized by the presence of chronic inflammation and oxidative stress, participating in the development of chronic vasculopathy and several chronic complications. The accumulation of hemoglobin and heme in the plasma, as a consequence of enhanced intravascular hemolysis, decreases nitric oxide bioavailability and enhances the production of reactive oxygen species (ROS). Heme and hemoglobin also represent erythrocytic danger-associated molecular pattern molecules (eDAMPs), which may activate endothelial inflammation through TLR-4 signaling and promote the development of complications, such as acute chest syndrome. It is also suspected that heme may activate the innate immune complement system and stimulate neutrophils to release neutrophil extracellular traps. A large amount of microparticles (MPs) from various cellular origins (platelets, RBCs, white blood cells, endothelial cells) is also released into the plasma of SCD patients and participate in the inflammation and oxidative stress in SCD. In turn, this pro-inflammatory and oxidative stress environment further alters the RBC properties. Increased pro-inflammatory cytokine concentrations promote the activation of RBC NADPH oxidase and, thus, raise the production of intra-erythrocyte ROS. Such enhanced oxidative stress causes deleterious damage to the RBC membrane and further alters the deformability of the cells, modifying their aggregation properties. These RBC rheological alterations have been shown to be associated to specific SCD complications, such as leg ulcers, priapism, and glomerulopathy. Moreover, RBCs positive for the Duffy antigen receptor for chemokines may be very sensitive to various inflammatory molecules that promote RBC dehydration and increase RBC adhesiveness to the vascular wall. In summary, SCD is characterized by a vicious circle between abnormal RBC rheology and inflammation, which modulates the clinical severity of patients.

11.
Front Physiol ; 10: 1329, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749708

RESUMO

Blood viscosity is an important determinant of local flow characteristics, which exhibits shear thinning behavior: it decreases exponentially with increasing shear rates. Both hematocrit and plasma viscosity influence blood viscosity. The shear thinning property of blood is mainly attributed to red blood cell (RBC) rheological properties. RBC aggregation occurs at low shear rates, and increases blood viscosity and depends on both cellular (RBC aggregability) and plasma factors. Blood flow in the microcirculation is highly dependent on the ability of RBC to deform, but RBC deformability also affects blood flow in the macrocirculation since a loss of deformability causes a rise in blood viscosity. Indeed, any changes in one or several of these parameters may affect blood viscosity differently. Poiseuille's Law predicts that any increase in blood viscosity should cause a rise in vascular resistance. However, blood viscosity, through its effects on wall shear stress, is a key modulator of nitric oxide (NO) production by the endothelial NO-synthase. Indeed, any increase in blood viscosity should promote vasodilation. This is the case in healthy individuals when vascular function is intact and able to adapt to blood rheological strains. However, in sickle cell disease (SCD) vascular function is impaired. In this context, any increase in blood viscosity can promote vaso-occlusive like events. We previously showed that sickle cell patients with high blood viscosity usually have more frequent vaso-occlusive crises than those with low blood viscosity. However, while the deformability of RBC decreases during acute vaso-occlusive events in SCD, patients with the highest RBC deformability at steady-state have a higher risk of developing frequent painful vaso-occlusive crises. This paradox seems to be due to the fact that in SCD RBC with the highest deformability are also the most adherent, which would trigger vaso-occlusion. While acute, intense exercise may increase blood viscosity in healthy individuals, recent works conducted in sickle cell patients have shown that light cycling exercise did not cause dramatic changes in blood rheology. Moreover, regular physical exercise has been shown to decrease blood viscosity in sickle cell mice, which could be beneficial for adequate blood flow and tissue perfusion.

12.
Eye (Lond) ; 33(12): 1939-1945, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31289356

RESUMO

BACKGROUND: The aim of the present work was to describe and compare multifocal electroretinogram findings (mfERG) between patients with sickle cell disease (SCD) without clinical sign of maculopathy and controls (HbAA). METHODS: Both HbSS (homozygous SCD) and HbSC (compound heterozygous SCD) patients, the two most frequent SCD genotypes, were included. All individuals underwent a full ophthalmologic examination (with a fundoscopy), a spectral domain ocular coherence tomography (SD-OCT) and a mfERG. RESULTS: A total of 86 subjects were included: 54 SCD patients (107 eyes) with 32 HbSS (63 eyes) and 22 HbSC (44 eyes) and 32 controls (64 eyes). None of the eyes showed retinal clinical abnormalities. SD-OCT analysis showed that macular thickness was statistically lower in SCD eyes than in controls. mfERG analysis demonstrated a significant reduction of N1 (initial-negative deflection), and P1 (positive peak) response amplitude densities of HbSS eyes compared to HbAA eyes from the centre (<2°) and to the periphery (>15°). Implicit time response was also reduced in the centre (<2°). N1 and P1 response amplitude densities of HbSC eyes were significantly lower than those of HbAA eyes from the centre (<2°) to the periphery (>15°). N1 implicit time was statistically reduced in HbSS compared to HbSC eyes. CONCLUSION: Our study is the first one to describe macular electrophysiological dysfunction in SCD patients. Moreover, we confirm that SCD maculopathy is equally frequent in HbSS and HbSC.

14.
Int J Neonatal Screen ; 5(1): 5, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33072965

RESUMO

The region surrounding the Caribbean Sea is predominantly composed of island nations for its Eastern part and the American continental coast on its Western part. A large proportion of the population, particularly in the Caribbean islands, traces its ancestry to Africa as a consequence of the Atlantic slave trade during the XVI-XVIII centuries. As a result, sickle cell disease has been largely introduced in the region. Some Caribbean countries and/or territories, such as Jamaica and the French territories, initiated newborn screening (NBS) programs for sickle cell disease more than 20 years ago. They have demonstrated the major beneficial impact on mortality and morbidity resulting from early childhood care. However, similar programs have not been implemented in much of the region. This paper presents an update of the existing NBS programs and the prevalence of sickle cell disease in the Caribbean. It demonstrates the impact of the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia (CAREST) on the extension of these programs. The presented data illustrate the importance of advocacy in convincing policy makers of the feasibility and benefit of NBS for sickle cell disease when coupled to early care.

15.
Clin Hemorheol Microcirc ; 71(3): 337-345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29865045

RESUMO

OBJECTIVE: Our study investigated the prevalence of retinopathy and maculopathy in sickle cell patients and tested the association between these two conditions. In addition, we tested whether hematological and hemorheological parameters, as well as genotype, were involved in the development of these two conditions. METHODS: Seventy sickle cell adult patients were recruited: 37 with sickle cell anemia (SCA) and 33 with sickle cell hemoglobin C disease (SCC). All patients underwent retinal examination and macular ocular coherence tomography. Blood was sampled for the measurements of hematological and hemorheological parameters. RESULTS: Twenty-six patients had maculopathy and 30 had retinopathy with no significant difference between SCA and SCC patients. No association between the presence of retinopathy and maculopathy was detected. RBC aggregation was higher and RBC deformability lower at 3 Pa in SCA patients. Blood viscosity and hematocrit were higher in SCC than in SCA patients. However, no association was found between biological parameters and the ocular complications studied. CONCLUSIONS: Our study showed that retinopathy and maculopathy are common in sickle cell disease. Nevertheless, we found no association with hematological parameters, blood rheology or genotype.


Assuntos
Anemia Falciforme/complicações , Viscosidade Sanguínea/fisiologia , Degeneração Macular/etiologia , Doenças Retinianas/etiologia , Reologia/métodos , Adulto , Anemia Falciforme/patologia , Feminino , Humanos , Degeneração Macular/patologia , Masculino , Doenças Retinianas/patologia
17.
Nitric Oxide ; 81: 28-35, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30342855

RESUMO

Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.


Assuntos
Anemia Falciforme/tratamento farmacológico , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hidroxiureia/farmacologia , Nitritos/sangue , Adulto , Eritrócitos/fisiologia , Feminino , Humanos , Masculino , Óxido Nítrico/sangue , Óxido Nítrico Sintase/metabolismo , Nitroprussiato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/sangue , Transdução de Sinais/efeitos dos fármacos
18.
Clin Hemorheol Microcirc ; 68(2-3): 165-172, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29614630

RESUMO

This review focuses on the contribution of abnormal blood rheology in the pathophysiology of sickle cell anemia (SCA). SCA is characterized by a reduction of red blood cell (RBC) deformability but this reduction is very heterogeneous among patients. Recent works have shown that patients with the lowest RBC deformability (measured by ektacytometry) have enhanced hemolysis and would be more prone to develop several complications such as priapism, leg ulcers and glomerulopathy. In contrast, patients with the highest deformability, and not under hydroxyurea therapy, seem to develop more frequently vaso-occlusive like events. Although less studied, RBC aggregation properties are very different between SCA and healthy individuals and it was demonstrated that increased RBC aggregates strength could be involved in some complications. Finally, several studies have established that the vascular system of SCA patients could not fully compensate any increase in blood viscosity because of the loss of vascular reactivity, which may result in vaso-occlusive crises.


Assuntos
Anemia Falciforme/sangue , Deformação Eritrocítica/fisiologia , Reologia/métodos , Feminino , Humanos , Masculino
19.
Clin Hemorheol Microcirc ; 68(2-3): 319-329, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29614639

RESUMO

Several pathophysiological pathways in sickle cell disease (SCD), the most prevalent hemoglobinopathy worldwide, result in activation of circulating blood cells and the release of submicron vesicles, so-called microparticles (MPs). MPs are candidate biomarkers in vascular disease that exhibit functional biological properties. Compared to healthy individuals, higher level of plasma MPs, mostly derived from platelets and red blood cells (RBC), has been repeatedly observed in SCD patients in their steady-state condition. In contrast, conflicting results have been obtained on the impact of SCD complications and hydroxyurea treatment on circulating MP concentrations, largely due to non-standardized pre- and analytical procedures. Several factors responsible for the increased release of MPs by RBC have been identified in SCD such as sickling/unsickling, oxidative stress and abnormal activity of RBC acid sphingomyelinase. Besides their well-known pro-coagulant effect, sickle RBC-derived MPs produced ex vivo can induce ROS production by endothelial cells and promote a pro-inflammatory and pro-adhesive phenotype that may lead to renal occlusion in SCD mice. However, the functional properties of circulating MPs in human sickle cell disease remain to be studied and fully characterized.


Assuntos
Anemia Falciforme/sangue , Micropartículas Derivadas de Células/metabolismo , Eritrócitos/metabolismo , Anemia Falciforme/fisiopatologia , Humanos
20.
Lipids Health Dis ; 17(1): 38, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29506549

RESUMO

BACKGROUND: The pathophysiology of sickle cell disease (SCD) and the variability of its clinical expression remain not fully understood, whether within or between different SCD genotypes. Recent studies have reported associations between lipid levels and several SCD complications. If lipid levels have been previously described as low in sickle cell anemia (SCA), few data have been provided for sickle cell SC disease (SCC). We designed our epidemiological study to isolate lipid levels and profiles by genotype in Guadeloupian cohorts of SCA and SCC adult patients, at steady state. We compared SCD lipid levels with those of the Guadeloupian general population (GGP), and analyzed potential associations between lipid levels and SCD complications (vaso-occlusive crises, acute chest syndrome and osteonecrosis). METHODS: Lipids, apolipoproteins, biological variables and anthropometric evaluation, were collected at steady state from medical files for 62 SCC and 97 SCA adult patients. Clinical SCD complications were collected from the clinical files. Analysis was conducted by genotype for all variables. RESULTS: Different SCC and SCA lipid profiles, both distinct from their GGP's, were identified. Compared to SCC and GGP, higher triglyceride (TG) levels were observed in SCA patients, independent of hydroxyurea, hemolysis, gender, age, body mass index (BMI), abdominal obesity and clinical nutritional status. Our survey highlights also subsequent anthropometrical phenotypes, with an over-representation of abdominal obesity with normal BMI in SCA patients, and affecting almost exclusively females in both genotypes. Moreover, more frequent positive history of acute chest syndrome (ACS) was observed in SCA patients with TG level higher than 1.50 g/l, and of osteonecrosis in SCC patients having non high-density lipoprotein-cholesterol level (Non HDL-C) higher than 1.30 g/l. CONCLUSIONS: This study reveals that SCA and SCC patients exhibit distinct lipid profiles and suggests that high TG and Non HDL-C levels are associated with past histories of ACS and osteonecrosis in SCA and SCC patients, respectively.


Assuntos
Anemia Falciforme/sangue , Lipídeos/sangue , Síndrome Torácica Aguda/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Guadalupe , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/sangue , Estudos Retrospectivos , Doenças Vasculares/sangue
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