scholarly journals Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1945
Author(s):  
Junaid Ansari ◽  
Felicity N. E. Gavins
Keyword(s):  
Serine Proteases ◽  
Ischemic Event ◽  
Effector Functions ◽  
Extracellular Traps ◽  
Obstructive Sleep ◽  
Clinical Strategies ◽  
Artery Disease ◽  
Cerebral Ischemic ◽  
Ischemic Events

Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, dyslipidemia, and sickle cell disease. Neutrophils can enable, as well as resolve, cerebrovascular inflammation via many effector functions including neutrophil extracellular traps, serine proteases and reactive oxygen species, and pro-resolving endogenous molecules such as Annexin A1. Like neutrophils, platelets also engage in pro- as well as anti-inflammatory roles in regulating cerebrovascular inflammation. These anucleated cells are at the core of stroke pathogenesis and can trigger an ischemic event via adherence to the hypoxic cerebral endothelial cells culminating in aggregation and clot formation. In this article, we review and highlight the evolving role of neutrophils and platelets in ischemic stroke and discuss ongoing preclinical and clinical strategies that may produce viable therapeutics for prevention and management of stroke.

scholarly journals Variations in the Presence of Carotid Intraplaque Hemorrhage Across Age Categories: What Age Groups Are Most Likely to Benefit From Plaque Imaging?

2020 ◽  
Vol 11 ◽  
Author(s):  
Anthony S. Larson ◽  
John C. Benson ◽  
Waleed Brinjikji ◽  
Luis Savastano ◽  
Giuseppe Lanzino ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Artery Disease ◽  
Age Groups ◽  
Intraplaque Hemorrhage ◽  
Plaque Imaging ◽  
Anterior Circulation ◽  
The Mean ◽  
Artery Disease ◽  
Cerebral Ischemic ◽  
Ischemic Events

Although carotid artery intraplaque hemorrhage (IPH) is a known risk-factor for cerebral ischemic events in patients of advanced age, its prevalence in younger cohorts is less certain. The purpose of this study was to assess the prevalence of carotid artery IPH across the age spectrum. A retrospective review was completed of all adult patients from our institution who underwent neck MRA with high-resolution carotid plaque imaging between 2017 and 2020. The mean ages of patients with and without IPH were calculated. The prevalence of IPH was compared between patients that were categorized into age groups. Patients with and without a cerebral ischemic event (e.g., stroke, retinal ischemia) were included. Unilateral anterior circulation ischemic events in patients without atrial fibrillation were presumed to be likely related to ipsilateral carotid artery disease. Multiple regression analysis was performed to determine independent associations with IPH. 634 patients were included (1,268 carotid arteries). Increasing age (OR: 1.04; 95% CI: 1.02–1.06; P = 0.001) was independently associated with IPH. 211 patients had unilateral anterior circulation ischemic events. The mean age of patients with carotid IPH was 71.4 years (SD = 9.9), compared to 62.8 years (SD = 15.8) of those without (P ≤ 0.0001). The prevalence of IPH increased with age in all patients (P = 0.0002). Among patients with ipsilateral anterior circulation ischemic events, each age category above 50 years had a significantly higher prevalence of IPH when compared to patients 18–50 years (P ≤ 0.05 for all comparisons). The prevalence of carotid IPH increases with age and is rare in patients under 50 years. The approximate threshold age for IPH development is likely around 50 years.

scholarly journals Thrombosis: tangled up in NETs

Blood ◽  
2014 ◽  
Vol 123 (18) ◽  
pp. 2768-2776 ◽  
Author(s):  
Kimberly Martinod ◽  
Denisa D. Wagner
Keyword(s):  
Cell Biology ◽  
Serine Proteases ◽  
Relevant Literature ◽  
Genetically Engineered ◽  
Peptidylarginine Deiminase ◽  
Extracellular Traps ◽  
Genetically Engineered Mice ◽  
Extracellular Release ◽  
Protein Components

Abstract The contributions by blood cells to pathological venous thrombosis were only recently appreciated. Both platelets and neutrophils are now recognized as crucial for thrombus initiation and progression. Here we review the most recent findings regarding the role of neutrophil extracellular traps (NETs) in thrombosis. We describe the biological process of NET formation (NETosis) and how the extracellular release of DNA and protein components of NETs, such as histones and serine proteases, contributes to coagulation and platelet aggregation. Animal models have unveiled conditions in which NETs form and their relation to thrombogenesis. Genetically engineered mice enable further elucidation of the pathways contributing to NETosis at the molecular level. Peptidylarginine deiminase 4, an enzyme that mediates chromatin decondensation, was identified to regulate both NETosis and pathological thrombosis. A growing body of evidence reveals that NETs also form in human thrombosis and that NET biomarkers in plasma reflect disease activity. The cell biology of NETosis is still being actively characterized and may provide novel insights for the design of specific inhibitory therapeutics. After a review of the relevant literature, we propose new ways to approach thrombolysis and suggest potential prophylactic and therapeutic agents for thrombosis.

scholarly journals Platelets, atherothrombosis, and atherosclerosis

2016 ◽  
Author(s):  
Karl Egan ◽  
Fionnuala Ni Ainle ◽  
Dermot Kenny
Keyword(s):  
Cardiovascular Disease ◽  
Antiplatelet Agents ◽  
Vascular Lesions ◽  
Atherosclerotic Plaques ◽  
Arterial Circulation ◽  
Chronic Inflammatory Condition ◽  
Artery Disease ◽  
Ischemic Events ◽  
Progression Of Atherosclerosis

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In 2008 alone, 17.3 million deaths (representing 30% of all deaths) were attributable to the complications of cardiovascular disease. Of these deaths, 7.3 million were due to coronary artery disease while 6.2 million were attributable to stroke. Cardiovascular disease is expected to remain the leading cause of death globally, with the number of deaths expected to reach 23.6 million annually by 2030 (WHO statistics, 2012). Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction (MI) and ischemic stroke. Platelets are the key cellular component of arterial thrombi with platelet adhesion under high shear conditions being central to atherothrombosis. In addition, platelets play a role in the progression of atherosclerosis. In this review, we will discuss the evidence for the role of platelets in atherothrombosis, notably the efficacy of antiplatelet agents in the prevention of ischemic events, and finally their role in the progression of atherosclerosis (atherogenesis).

scholarly journals Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Gierlikowska ◽  
Albert Stachura ◽  
Wojciech Gierlikowski ◽  
Urszula Demkow
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Innate Immune ◽  
Therapeutic Approaches ◽  
Effector Functions ◽  
Pharmacological Modulation ◽  
Synthetic Drugs ◽  
Extracellular Traps

Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.

Abstract 2676: Lipoprotein associated-phospholipase A2 Activity Level is Increased in Acute Cerebral Ischemic Events

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Waimei A Tai ◽  
Charlene Chen ◽  
Michael Mlynash ◽  
Demi Thai ◽  
Neil Schwartz ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Infarct Volume ◽  
Activity Level ◽  
Activity Levels ◽  
Large Artery ◽  
Ischemic Lesion ◽  
Ischemic Event ◽  
Blood Samples ◽  
Cerebral Ischemic ◽  
Ischemic Events

Introduction: Lipoprotein associated -phospholipase A2 (Lpa-A2) mass and activity can help identify high risk TIA patients. We evaluate the yield of Lpa-A2 mass and activity to differentiate acute cerebral ischemic events from non-ischemic events. Methods: From July 2007 to March 2009, 48 patients presenting to the Stanford Unversity Medical Center Emergency room with stroke or TIA symptoms were prospectively enrolled and blood samples were obtained at time of presentation, 24 hours, and 72 hours after presentation. Blood samples were analyzed for Lpa-A2 mass and activity using commercially available assays (diaDexus, Inc). Patients with final diagnosis of stroke or TIA were classified as ischemic and others as non-ischemic. The size of the ischemic lesion was measured among stroke patients on diffusion weighted imaging (DWI). Results: Twenty eight patients (58%) had a diagnosis of brain infarction [median NIHSS=7 (IQR=4-12)], 9 (19%) had a diagnosis of TIA [median ABCD2=4, (IQR=3-6)] and 11(23%) had a non ischemic event (1 peripheral vertigo, 2 infections, 3 seizures, 4 peripheral neuropathy/myopathy, 1 multiple sclerosis relapse). Among the 37 ischemic patients, stroke mechanisms were according to TOAST criteria: 6 (16%) large artery atherosclerosis, 21 (57%) cardioembolic, 1 (3%) small artery, 4 (11%) other determined and 5 (13%) undetermined. At admission, Lpa-A2 activity level was higher among patients experiencing an ischemic event (stroke or TIA) compared to non ischemic event (p=0.007). Among ischemic patients, Lpa-A2 activity measured at admission was lower than the activity measured at day 1 (p=0.006) and day 3 (p=0.002) and was stable among non ischemic patients. Among the 24 ischemic patients who underwent acute MRI and were found to have an ischemic lesion on DWI, there was no relation between Lpa-A2 activity level and infarct volume. Lipoprotein associated -phospholipase A2 mass level was not different between ischemic and non ischemic patients. The mass levels remained stable over time in each group and were not related to infarct volume. Conclusions: Lpa-A2 activity levels were higher among ischemic patients compared with non ischemic etiologies. Lpa-A2 activity levels rose during the first days after brain ischemia. This exploratory data suggests Lpa-A2 activity level could possibly help physicians discriminate cerebral ischemic from non ischemic events. Further research is warranted and ongoing.

Neutrophils are key mediators in crescentic glomerulonephritis and targets for new therapeutic approaches

2020 ◽  
Author(s):  
Marilina Antonelou ◽  
Rhys D R Evans ◽  
Scott R Henderson ◽  
Alan D Salama
Keyword(s):  
Serine Proteases ◽  
Crescentic Glomerulonephritis ◽  
Antigen Expression ◽  
Therapeutic Approaches ◽  
Extracellular Traps ◽  
New Therapeutic Approaches ◽  
Self Tolerance ◽  
Wide Range ◽  
Neutrophil Degranulation

Abstract Crescentic glomerulonephritis (CGN) results from a diverse set of diseases associated with immune dysregulation and the breakdown of self-tolerance to a wide range of autoantigens, some known and some that remain unknown. Experimental data demonstrate that neutrophils have an important role in the pathogenesis of CGN. Upon activation, neutrophils generate reactive oxygen species, release serine proteases and form neutrophil extracellular traps (NETs), all of which can induce direct tissue damage. In addition, serine proteases such as myeloperoxidase and proteinase 3, presented on NETs, can be processed and recognized as autoantigens, leading to the generation and maintenance of autoimmune responses in susceptible individuals. The basis of the specificity of autoimmune responses in different patients to NET proteins is unclear, but relates at least in part to differences in human leucocyte antigen expression. Conditions associated with CGN are often characterized by aberrant neutrophil activation and NETosis and, in some, impaired NET degradation. Targeting neutrophil degranulation and NETosis is now possible using a variety of novel compounds and may provide a promising therapeutic alternative to glucocorticoid use, which has been a mainstay of management in CGN for decades and is associated with significant adverse effects. In this review, we discuss the evidence supporting the role of neutrophils in the development of CGN and the pathways identified in neutrophil degranulation and NETosis that may translate to novel therapeutic applications.

scholarly journals Platelets, atherothrombosis, and atherosclerosis

2016 ◽  
Author(s):  
Karl Egan ◽  
Fionnuala Ni Ainle ◽  
Dermot Kenny
Keyword(s):  
Cardiovascular Disease ◽  
Antiplatelet Agents ◽  
Vascular Lesions ◽  
Atherosclerotic Plaques ◽  
Arterial Circulation ◽  
Chronic Inflammatory Condition ◽  
Artery Disease ◽  
Ischemic Events ◽  
Progression Of Atherosclerosis

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In 2008 alone, 17.3 million deaths (representing 30% of all deaths) were attributable to the complications of cardiovascular disease. Of these deaths, 7.3 million were due to coronary artery disease while 6.2 million were attributable to stroke. Cardiovascular disease is expected to remain the leading cause of death globally, with the number of deaths expected to reach 23.6 million annually by 2030 (WHO statistics, 2012). Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction (MI) and ischemic stroke. Platelets are the key cellular component of arterial thrombi with platelet adhesion under high shear conditions being central to atherothrombosis. In addition, platelets play a role in the progression of atherosclerosis. In this review, we will discuss the evidence for the role of platelets in atherothrombosis, notably the efficacy of antiplatelet agents in the prevention of ischemic events, and finally their role in the progression of atherosclerosis (atherogenesis).

scholarly journals The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases

2018 ◽  
Vol 118 (01) ◽  
pp. 006-027 ◽  
Author(s):  
Aldo Bonaventura ◽  
Luca Liberale ◽  
Federico Carbone ◽  
Alessandra Vecchié ◽  
Candela Diaz-Cañestro ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Inflammatory Diseases ◽  
Vascular Diseases ◽  
Neutrophil Extracellular Traps ◽  
Human Beings ◽  
Coronary Syndrome ◽  
Extracellular Traps ◽  
Atherosclerotic Lesions ◽  
Autoimmune And Inflammatory Diseases

AbstractNeutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli. NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes. Neutrophil dysregulation has been demonstrated in the pathogenesis of most representative vascular diseases, such as acute coronary syndrome, stroke and venous thrombosis. Indeed, NETs have been identified within atherosclerotic lesions and arterial thrombi in both human beings and animal models. Moreover, an imbalance in this mechanism has been proposed as a critical source of modified and/or externalized autoantigens in autoimmune and inflammatory diseases. Finally, an update on the role of NETs in the pathogenesis of cancer has been included. In the present review, based on papers released on PubMed and MEDLINE up to July 2017, we point to update the knowledge on NETs, from their structure to their roles in infectious diseases as well as in cardiovascular diseases, autoimmunity, metabolic disorders and cancer, with a look to future perspectives and therapeutic opportunities.

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