Cardiovascular & Haematological Disorders - Drug Targets - Volume 17, Issue 3, 2017

Background: The impact of diet strategies to manage cardiovascular disease has been focused in recent years. The food ingredients, such as flavonoids, are known as cardioprotective agents; however, it is not fully understood how these compounds are effective against cardiovascular problems. Catechins are polyphenolic compounds exhibiting several biological activities in the human body, potentially in the treatment of cardiovascular disease. The present study indicates that catechins may be effective against cardiovascular problems through modulating blood lipid metabolism, protecting vascular endothelial, and decreasing blood pressure. Conclusion: The current review has evaluated various studies on the role of catechins in the prevention and treatment of cardiovascular disorders by focusing on oxidative stress and inflammatory responses.

Background: Myeloproliferative neoplasms (MPNs) are chronic blood disorders caused by clonal expansion in one or more myeloid lineages and include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and chronic myeloid leukemia (CML). Cardiovascular events are a main challenge for patients with MPN and can lead to their death. Objective: JAK2V617F mutation is observed in Philadelphia-negative MPNs such as ET and PV, increasing the risk of cardiovascular complications in these patients. JAK2 mutation can affect cardiac arteries and veins in ET and PV, which results in thrombosis, ischemia and other cardiovascular events. JAK/STAT signaling pathway plays an important role in heart diseases. In this review, we will survey the cardiovascular events in JAK2-positive MPN patients. Method: Relevant English-language literature were searched and retrieved from PubMed search engine (1995–2017). The following keywords were used: “Cardiovascular Events”, “JAK2” and “Myeloproliferative Neoplasms”. Forty three articles were selected by using the key words. Results: JAK2 phosphorylates the signal transducers and activators of transcription (STAT). Various factors like angiotensin II (ANG II) and cardiotrophin-1 (CT-1) can bind their receptors on myocytes and increase the expression of angiotensinogen (Ao) gene by binding of STAT proteins to these factors in myocytes, causing different cardiovascular complications through autocrine mechanisms. Conclusion: JAK2 mutation is observed in patients with thrombosis, ischemia and other cardiovascular complications having abnormal increase in cell count even without definite clinical diagnosis of MPN. Therefore, identification of this mutation in these patients contributes to definite diagnosis of cardiovascular events. Also, cardiovascular complications in MPN patients can be prevented by targeting the factors involved in JAK/STAT signaling pathway.

Background: Viscoelastic tests (VETs) such as thromboelastography, rotational thromboelastography, and the Sonoclot Analyzer assess the entire process of clot formation through dissolution in real-time, and may provide additional therapeutic value to conventional laboratory coagulation tests. With the ability to obtain rapid results and identify specific coagulopathies, VETs has been examined in a variety of clinical scenarios, including cardiac surgery, trauma, obstetric emergencies, and liver transplant. Conclusion: This review provides a summary of clinical trials utilizing VETs in the aforementioned clinical scenarios, and suggests that VETs have demonstrated a capability to identify coagulopathies, utility in guiding algorithms to reduce the amount of transfusions, and a limited ability to predict bleeding events or mortality.

Introduction: Patients with severe thrombocytopenia are presumed to be at increased risk for bleeding, and consequently it has been a standard practice for the past four decades to give allogeneic platelet transfusions to severely thrombocytopenic patients as supportive care. Platelet transfusions may be given either prophylactically to reduce the risk of bleeding, in the absence of clinical hemorrhage (prophylactic transfusions), or to control active bleeding when present (therapeutic transfusions). Conclusion: Here we review the structure and function of platelets and discuss the mechanisms of alloimmunization to platelet transfusion.

Objective: Exosomes are small secreted membrane vesicles formed in the late endocytic compartments by inward budding. Interest in these extracellular vesicles and their role in atherosclerosis is growing, as they can affect multiple cellular processes that lead to lipid overload, cytokine secretion and cellular adhesion. Exosomes protect and transport lipids, proteins, and RNAs, fostering intercellular communication among different cell types involved in atherogenesis such as macrophages, endothelium and smooth muscle. Their molecular composition reflects their cell type of origin, but they share attributes because they are enriched in proteins of their endosomal source. Conclusion: This review will describe the current state of our knowledge of exosome involvement in the development of atherosclerosis. The transfer of signaling molecules, lipids, mRNAs, and microRNAs via exosomes with effects on monocyte and macrophage cholesterol metabolism, endothelial cell and platelet activation and smooth muscle proliferation will be discussed. Finally, therapeutic potential of exosomes and clinical application will be explored.

Aims: Atrial fibrillation (AF) ablation is associated with increased circulating markers of inflammation. Innate immune or inflammation pathways up-regulate mononuclear cell responses and may increase the risk for recurrent arrhythmia. Chemokines and serine protease coagulation pathways both activate innate immune responses. Here, we measured inflammatory markers in peripheral blood samples from patients after cryoballoon and/or radiofrequency pulmonary vein isolation and assessed the capacity for the inhibition of chemokine and serine protease pathways to block cell activation. Methods: Markers of inflammation were measured in 55 patients immediately before and one day after AF ablation. Peripheral blood mononuclear cells (PBMCs) isolated from 19 patients were further tested for responsiveness to two anti-inflammatory proteins ex vivo using fluorescence assays and RT-qPCR analysis of gene expression. Results: White blood cells (WBC), C-reactive protein, fibrinogen and troponin T levels were significantly elevated after ablation. PBMCs isolated from the circulating blood had increased activation with Phorbol 12-myristate 13-acetate. Cell activation, as measured by membrane fluidity, was blunted after treatment with a broad-spectrum chemokine modulating protein, M-T7, which interferes with chemokine/glycosaminoglycan (GAG) interactions, but not by Serp-1, a serine protease inhibitor (serpin) that targets both thrombotic and thrombolytic pathway proteases. Differential gene expression changes in the apoptotic pathway were identified with M-T7 and Serp-1. Conclusions: Patients undergoing AF ablation have significantly increased inflammatory markers. Inhibition of chemokine signaling, but not serine proteases, reduced the activation of monocytes isolated from patients, in vitro. Targeting chemokines have the potential to reduce post-ablation activation of circulating leukocytes.

Background: Venous thromboemboli tend to recur. However, the causative factors underlying pulmonary embolism recurrence are not well defined. Aims: To explore the factors associated with pulmonary embolism recurrence. Patients and Methods: Patients diagnosed with pulmonary emboli between 2004 and 2013 at our institution were enrolled. Duration of anticoagulant therapy, new episodes of venous thromboembolism, and deaths were recorded. Results: Pulmonary embolism was diagnosed in 528 patients (median age: 76 years, interquartile range [IQR]: 16; male: 45%). The median follow-up time was 34 months (IQR: 52). In total, 477 patients completed ≥3 months of anticoagulation therapy. Permanent anticoagulation was indicated in 217 (45%) patients, and therapy was discontinued in 260 (55%) patients. Overall, 79 patients experienced a recurrence (5.6 per patient-year). Recurrence was significantly associated with anticoagulation discontinuation (4% vs. 27% of patients who maintained or discontinued therapy, respectively; P<0.001; 95% confidence interval -0.95, -0.86). The median duration between anticoagulation withdrawal and recurrence was 6.5 months (IQR: 23.25). Factors associated with recurrence were unprovoked pulmonary embolism (odds ratio [OR]: 0.45), a greater degree of pulmonary arterial obstruction (OR: 2.5), a delay in initiation of anticoagulation (OR: 3), and higher plasma D-dimer levels during treatment (OR: 2.3). Survival rates were improved for patients who maintained anticoagulation therapy relative to those who discontinued. Conclusion: Pulmonary embolism has a high recurrence rate. Permanent anticoagulant therapy should be considered for patients with idiopathic pulmonary embolism, a high thrombotic burden, and persistently elevated D-dimer levels during treatment, and for patients where therapy was initially delayed.

Background: In the general population the leading cause of cardioembolic stroke is atrial fibrillation (AF). A silent AF is also the possible cause of many cryptogenic strokes. P wave dispersion (PWD), a predictor of AF, has been proposed as a marker of silent AF occurrence in these strokes. PWD correlates with high-sensitive C-reactive protein levels reflecting the role of inflammation in promoting a slowed and inhomogeneous atrial conduction. Statins have a multitude of additional effects beyond lipid lowering, in particular anti-inflammatory effects that may influence atrial conduction. Objective: The aim of this study was to evaluate the effects of previous statin use on PWD in patients with cryptogenic stroke, in order to highlight a possible role for statins in preventing atrial conduction alterations that predispose to AF. Method: We enrolled 131 patients (67 males, 64 females; mean age 69±13 years) with cryptogenic stroke. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. PWD was measured in all subjects. Results: Patients previously treated with statins (n: 34) had lower PWD and P index values in comparison with no-statin group (41.7±12.2 vs 48.7±15.2 ms, p=0.01, and 14.2±3.7 vs 16.5±5.3 ms, p=0.02, respectively). Conclusions: Our results show lower PWD values in cryptogenic stroke patients previously treated with statins. These findings provide support to the hypothesis that statins may play a role in modulating atrial electrophysiological and structural properties, preventing the occurrence of a slowed and heterogeneous atrial conduction and finally, reducing the occurrence of AF.