Sickle‐cell disease and the heart: review of the current literature

Voskaridou, Ersi; Christoulas, Dimitrios; Terpos, Evangelos

doi:10.1111/j.1365-2141.2012.09143.x

Cited by 80 publications

(94 citation statements)

References 112 publications

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“…Moreover, SCD mice showed increased cardiac output and aortic valve peak pressure that were 2.8-and 4.5-fold higher, respectively, VIIc and VIId and Table III in the online-only Data Supplement). Increased blood pressure and cardiac output 35 were found to be associated with an increased hypertrophic response and a significant reduction in myocardial performance 36 (Table III in the online-only Data Supplement).…”

Section: Hx Therapy Normalizes Blood Pressure and Improves Cardiac Fumentioning

confidence: 99%

Hemopexin Therapy Improves Cardiovascular Function by Preventing Heme-Induced Endothelial Toxicity in Mouse Models of Hemolytic Diseases

et al. 2013

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Background-Hemolytic diseases are characterized by enhanced intravascular hemolysis resulting in heme-catalyzed reactive oxygen species generation, which leads to endothelial dysfunction and oxidative damage. Hemopexin (Hx) is a plasma heme scavenger able to prevent endothelial damage and tissue congestion in a model of heme overload. Here, we tested whether Hx could be used as a therapeutic tool to counteract heme toxic effects on the cardiovascular system in hemolytic diseases. Methods and Results-By using a model of heme overload in Hx-null mice, we demonstrated that heme excess in plasma, if not bound to Hx, promoted the production of reactive oxygen species and the induction of adhesion molecules and caused the reduction of nitric oxide availability. Then, we used β-thalassemia and sickle cell disease mice as models of hemolytic diseases to evaluate the efficacy of an Hx-based therapy in the treatment of vascular dysfunction related to heme overload. Our data demonstrated that Hx prevented heme-iron loading in the cardiovascular system, thus limiting the production of reactive oxygen species, the induction of adhesion molecules, and the oxidative inactivation of nitric oxide synthase/nitric oxide, and promoted heme recovery and detoxification by the liver mainly through the induction of heme oxygenase activity. Moreover, we showed that in sickle cell disease mice, endothelial activation and oxidation were associated with increased blood pressure and altered cardiac function, and the administration of exogenous Hx was found to almost completely normalize these parameters. 12,13,16 In hemolytic diseases, the high rate of hemolysis results in the saturation and depletion of the plasma Hb/heme scavenging systems 17 and leads to a buildup of Hb and heme in the circulation that mediates pro-oxidant and proinflammatory effects on vessel endothelial cells. Conclusions-Hemopexin 18Although many mechanisms contribute to the complex pathophysiology of hemolytic diseases as SCD and β-thalassemia, a unifying theme is represented by the dysfunction of the vascular endothelium and the highly pro-oxidant plasma environment. 1,[19][20][21][22] SCD is characterized by recurring episodes of painful vasoocclusion, leading to ischemia/reperfusion injury and organ damage.6,23 Endothelial dysfunction, inflammation, and activated monocytes, neutrophils, platelets, and dense red cells all contribute to sickle cell crisis.4,23 β -Thalassemia is frequently complicated by thromboembolic events resulting from coagulation abnormalities and damaged red cells exposing phosphatidylserine, to which endothelial activation and oxidative stress strongly contribute. 3,23,24 Moreover, severe forms of SCD and β-thalassemia require a blood transfusion regimen that further increases the amount of circulating Hb/heme, thus exacerbating oxidative stress. 25,26 Although an iron chelation therapy is routinely associated with a transfusion regimen, 27,28 no heme chelation therapy has been developed to date that specifically prevents heme-induced endot...

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Section: Hx Therapy Normalizes Blood Pressure and Improves Cardiac Fumentioning

confidence: 99%

Hemopexin Therapy Improves Cardiovascular Function by Preventing Heme-Induced Endothelial Toxicity in Mouse Models of Hemolytic Diseases

et al. 2013

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“…Contributing pathways to the development of these complications including the role of hemolysis and heme-based injury, the vascular endothelium, the effects of hypoxia and inflammation-and immune-mediated cell activation have been extensively studied. [1][2][3][4][5][6][7] Despite its Mendelian inheritance, the course of patients with SCD is highly variable. There is significant heterogeneity in the rate of development of acute and chronic pain, cerebrovascular disease, acute chest syndrome, 8,9 pulmonary hypertension (PH), diastolic dysfunction, renal failure, hemolytic anemia, and premature or sudden death.…”

Section: Introductionmentioning

confidence: 99%

Association of circulating transcriptomic profiles with mortality in sickle cell disease

Desai

Lei

Bahroos

et al. 2017

Blood

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• We validated the association of a circulating genome-wide gene expression profile with poor outcomes in 3 cohorts of SCD.• A composite risk score using this genomic biomarker with clinical risk factors exhibited improved prediction than clinical factors alone.Sickle cell disease (SCD) complications are associated with increased morbidity and risk of mortality. We sought to identify a circulating transcriptomic profile predictive of these poor outcomes in SCD. Training and testing cohorts consisting of adult patients with SCD were recruited and prospectively followed. A pathway-based signature derived from grouping peripheral blood mononuclear cell transcriptomes distinguished 2 patient clusters with differences in survival in the training cohort. These findings were validated in a testing cohort in which the association between cluster 1 molecular profiling and mortality remained significant in a fully adjusted model. In a third cohort of West African children with SCD, cluster 1 differentiated SCD severity using a published scoring index. Finally, a risk score composed of assigning weights to cluster 1 profiling, along with established clinical risk factors using tricuspid regurgitation velocity, white blood cell count, history of acute chest syndrome, and hemoglobin levels, demonstrated a higher hazard ratio for mortality in both the training and testing cohorts compared with clinical risk factors or cluster 1 data alone. Circulating transcriptomic profiles are a powerful method to risk-stratify severity of disease and poor outcomes in both children and adults, respectively, with SCD and highlight potential associated molecular pathways. (Blood. 2017;129(22):3009-3016)

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“…This frequency sweep technique was further extended to negatively charged biconcave red blood cells (RBCs), which are an important cellular system for medical disease diagnostics. [36][37][38] …”

Section: Introductionmentioning

confidence: 99%

Frequency sweep rate dependence on the dielectrophoretic response of polystyrene beads and red blood cells

2013

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Alternating current (AC) dielectrophoresis (DEP) experiments for biological particles in microdevices are typically done at a fixed frequency. Reconstructing the DEP response curve from static frequency experiments is laborious, but essential to ascertain differences in dielectric properties of biological particles. Our lab explored the concept of sweeping the frequency as a function of time to rapidly determine the DEP response curve from fewer experiments. For the purpose of determining an ideal sweep rate, homogeneous 6.08 lm polystyrene (PS) beads were used as a model system. Translatability of the sweep rate approach to $7 lm red blood cells (RBC) was then verified. An Au/Ti quadrapole electrode microfluidic device was used to separately subject particles and cells to 10Vpp AC electric fields at frequencies ranging from 0.010 to 2.0 MHz over sweep rates from 0.00080 to 0.17 MHz/s. PS beads exhibited negative DEP assembly over the frequencies explored due to Maxwell-Wagner interfacial polarizations. Results demonstrate that frequency sweep rates must be slower than particle polarization timescales to achieve reliable incremental polarizations; sweep rates near 0.00080 MHz/s yielded DEP behaviors very consistent with static frequency DEP responses for both PS beads and RBCs. V C 2013 AIP Publishing LLC.

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Sickle‐cell disease and the heart: review of the current literature

Cited by 80 publications

References 112 publications

Hemopexin Therapy Improves Cardiovascular Function by Preventing Heme-Induced Endothelial Toxicity in Mouse Models of Hemolytic Diseases

Hemopexin Therapy Improves Cardiovascular Function by Preventing Heme-Induced Endothelial Toxicity in Mouse Models of Hemolytic Diseases

Association of circulating transcriptomic profiles with mortality in sickle cell disease

Frequency sweep rate dependence on the dielectrophoretic response of polystyrene beads and red blood cells

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