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Journal of Cardiovascular Pharmacology 1996Platelet adherence to structurally or functionally damaged endothelium and its subsequent activation are multifaceted events. Regulation of the rate and extent of... (Review)
Review
Platelet adherence to structurally or functionally damaged endothelium and its subsequent activation are multifaceted events. Regulation of the rate and extent of platelet adhesion is under local control by the platelets and endothelium. Even in the absence of platelet adhesion to endothelium or subendothelium, there is a complex hemostatic balance of coagulation and anticoagulation. This is mediated by the manufacture, release, and inactivation of various procoagulant and anticoagulant compounds, predominantly by the platelets and endothelium. The relationship between the two in maintaining the homeostasis of coagulation and other processes is complex. This review focuses on the structure, function, and interaction of endothelium, subendothelium, and platelets and on their vasoactive and pro-/anticoagulant functions.
Topics: Animals; Blood Coagulation; Blood Platelets; Endothelium, Vascular; Humans; Platelet Activation; Platelet Adhesiveness; Thrombosis
PubMed: 8938279
DOI: 10.1097/00005344-199600001-00006 -
Indian Journal of Physiology and... Oct 1993Blood platelets interact with a variety of soluble agonists such as epinephrine and adenosine diphosphate (ADP); many insoluble cell matrix components, including... (Review)
Review
Blood platelets interact with a variety of soluble agonists such as epinephrine and adenosine diphosphate (ADP); many insoluble cell matrix components, including collagen and laminin, and biomaterials used for construction of invasive medical devices. These interactions stimulate specific receptors and glycoprotein-rich domains (integrins and nonintegrin) on the plasma membrane and lead to the activation of intracellular effector enzymes. The majority of regulatory events appear to require free calcium. Ionized calcium is the primary bioregulator, and a variety of biochemical mechanisms modulate the level and availability of free cytosolic calcium. Major enzymes that regulate the free calcium levels via second messengers include phospholipase C, phospholipase A2, and phospholipase D, together with adenylyl and guanylyl cyclases. Activation of phospholipase C results in the hydrolysis of phosphatidyl inositol 4,5-bisphosphate and formation of second messengers 1,2-diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diglyceride induces activation of protein kinase C, whereas IP3 mobilizes calcium from internal membrane stores. Elevation of cytosolic calcium stimulates phospholipase A2 and liberates arachidonic acid. Free arachidonic acid is transformed to a novel metabolite, thromboxane A2, by fatty acid synthetases. Thromboxane A2 is the major metabolite of this pathway and plays a critical role in platelet recruitment, granule mobilization and secretion. Up-regulation in signalling pathways will increase the risk for clinical complications associated with thromboembolic episodes. Down-regulation of signal transduction mechanisms may precipitate bleeding diathesis or stroke.
Topics: Blood Platelets; Calcium; Humans; Phosphatidylinositols; Phospholipases; Platelet Activation; Platelet Aggregation; Second Messenger Systems; Signal Transduction
PubMed: 8112802
DOI: No ID Found -
Journal of Clinical Periodontology Sep 2018Periodontitis results in platelet activation and enhanced risk for cardiovascular disease. As it is currently unknown whether periodontal treatment reverses platelet... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
Periodontitis results in platelet activation and enhanced risk for cardiovascular disease. As it is currently unknown whether periodontal treatment reverses platelet hyper-reactivity, we aimed to investigate the role of periodontal treatment on platelet activation.
MATERIALS AND METHODS
In a prospective controlled therapeutic trial, 52 patients were enrolled and randomly selected for periodontal treatment or monitored without treatment for 3 months. Patient blood was analysed by flow cytometry for platelet activation markers and by light transmission aggregometry for platelet aggregation in response to pro-thrombotic stimuli.
RESULTS
In this study, platelet activation in the control group aggravated over the observation period of 3 months, whereas patients that underwent periodontal treatment showed unchanged levels of platelet activation, measured by surface expression of CD62P, CD40L, generation of reactive oxygen production, activation of GPIIb/IIIa and fibrinogen binding. Moreover, platelet turnover, measured by platelet RNA content and platelet aggregation in response to collagen, differed significantly between patients that were treated and those who were untreated.
CONCLUSIONS
Subgingival debridement reduces the risk of aggravated platelet activation and therefore might potentially diminish subsequent diseases such as cardiovascular disease in periodontal patients.
Topics: Humans; Periodontitis; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies
PubMed: 29972709
DOI: 10.1111/jcpe.12980 -
The Annals of Thoracic Surgery Jan 1990My colleagues and I have employed a simulated extracorporeal circuit to help define blood cell changes during clinical cardiopulmonary bypass. Platelet count decreases... (Review)
Review
My colleagues and I have employed a simulated extracorporeal circuit to help define blood cell changes during clinical cardiopulmonary bypass. Platelet count decreases sharply due to temporary adhesion to the circuit. Platelets degranulate, synthesize and release thromboxane A2, and lose the ability to aggregate with adenosine diphosphate and epinephrine. These changes are also due to the loss of alpha 2-adrenergic and fibrinogen receptors. The neutrophil count decreases to a lesser extent, but neutrophils also are stimulated to secrete lactoferrin and elastase concomitant with activation of plasma kallikrein. Although lidocaine can inhibit the neutrophil activation and prostacyclin can inhibit the platelet stimulation, prostaglandin E1 appears to prevent both neutrophil and platelet alterations.
Topics: Cardiopulmonary Bypass; Humans; Neutrophils; Platelet Activation; Surface Properties
PubMed: 2404474
DOI: 10.1016/0003-4975(90)90352-7 -
Seminars in Thrombosis and Hemostasis Aug 2003Healthy newborns maintain normal circulating platelet counts, with a platelet ultrastructure that does not differ from adults. In vitro assessments of intrinsic platelet... (Review)
Review
Healthy newborns maintain normal circulating platelet counts, with a platelet ultrastructure that does not differ from adults. In vitro assessments of intrinsic platelet function, however, have demonstrated transient hyporesponsiveness that is most marked in platelets from preterm infants. Decreased responses were originally considered to be the result of platelet activation and degranulation during labor and delivery, but more recent studies of platelet activation markers have not supported this theory. Decreased activation responses are due to relative deficiencies of phospholipid metabolism, calcium mobilization, granule secretion, and aggregation. These result in turn from differences in intrinsic signal transduction in the neonatal platelet compared with the adult. In contrast, there is enhanced platelet adhesion due to the presence in neonatal plasma of larger, more functionally potent von Willebrand factor multimers. These ultralarge multimers may result from decreased activity of von Willebrand factor-cleaving protease in neonatal plasma and are associated with shorter bleeding times and Platelet Function Analyser-100 closure times in neonates. In the immediate newborn period, this enhanced platelet adhesion may compensate for the decreased intrinsic platelet activation in healthy neonates, but may leave sick neonates at increased risk of bleeding.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Infant, Newborn; Platelet Activation; Platelet Function Tests; Signal Transduction
PubMed: 14517748
DOI: 10.1055/s-2003-42587 -
Chest Sep 2016
Topics: Antibodies; Anticoagulants; Heparin; Humans; Platelet Activation; Platelet Factor 4; Thrombocytopenia
PubMed: 27613972
DOI: 10.1016/j.chest.2016.04.001 -
Expert Review of Anticancer Therapy Aug 2008Platelets are highly reactive components of the circulatory system, which exert not only haemostatic activity but also contribute to the modulation of various... (Review)
Review
Platelets are highly reactive components of the circulatory system, which exert not only haemostatic activity but also contribute to the modulation of various pathological conditions including inflammation, atherosclerosis and cancer metastasis through the release of cytokines, chemokines and the presentation of several adhesion molecules. During cancer metastasis, the formation of platelet-tumor cell aggregates in the circulation facilitates immune evasion and the microvascular arrest of tumor cells at distant sites. Several adhesion molecules, such as integrins and glycoproteins, were shown to be involved in this process. Recent findings indicate that P-selectin is another main mediator of platelet-tumor cell interactions. Other effects of activated platelets on cancer progression are associated with a release of platelet-derived factors stimulating tumor growth and angiogenesis. Any interference in platelet-tumor cell interactions resulted in attenuation of cancer metastasis. The well recognized, albeit not fully characterized function of platelets during cancer progression defines platelets as potential targets for cancer therapy. Specifically, the rapid expression of P-selectin on the cell surface of activated platelets and its strong association with metastasis provide a rationale for P-selectin inhibition as an antimetastatic treatment.
Topics: Hemostasis; Humans; Neoplasm Metastasis; Neoplasms; Platelet Activation; Platelet Aggregation
PubMed: 18699763
DOI: 10.1586/14737140.8.8.1247 -
Current Medicinal Chemistry 2005Platelet activation plays an important role in a wide range of pathological conditions. For example, platelet activation has been shown to be involved in the defence... (Review)
Review
Platelet activation plays an important role in a wide range of pathological conditions. For example, platelet activation has been shown to be involved in the defence against parasitic infection, the pathogenesis of atherosclerotic disease, and various arterial and venous thrombotic diseases. Indeed, there is considerable interest in the manipulation of platelet function for therapeutic gain. It is for these reasons that there is considerable interest in developing assays measuring in vivo platelet activation. Current modalities in the measurement of platelet activation include Enzyme-linked Immunosorbent Assays (ELISA), platelet flow cytometry and electron microscopy. It is proposed that methods in measuring platelet activation can also be classified into 'direct' and 'indirect' modalities, both of which have their distinct advantages and disadvantages. Unfortunately, there is at present no consensus on the ideal method of measuring platelet activation. Thus, studies on platelet activation should ideally include at least one of each of direct and indirect modality of studying platelet activation. This review provides an overview of basic platelet biology and the various methods of measuring platelet activation, with an emphasis on their role in drug development.
Topics: Animals; Biomarkers; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Microscopy, Electron; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests
PubMed: 16375705
DOI: 10.2174/092986705774933399 -
Cerebrovascular Diseases (Basel,... 2015Platelet-leukocyte aggregation (PLA) and platelet activation are found to be on the higher side in ischemic stroke patients. The correlation of PLA with clinical...
BACKGROUND
Platelet-leukocyte aggregation (PLA) and platelet activation are found to be on the higher side in ischemic stroke patients. The correlation of PLA with clinical features has not been intensively investigated and the influence of genetic factors on PLA is still unexplored. The interaction of platelets with leukocytes is mainly determined by the proteins encoded by six genes: P-Selectin (SELP encodes CD62P) on the thrombocyte binding to P-Selectin-Glycoprotein-Ligand-1 (PSGL1) on the leukocyte, intracellular-adhesion-molecule 2 (ICAM2) interacting with Integrin alpha M (ITGAM) and Glycoprotein 1b-alpha (GP1BA) binding to Integrin alpha L (ITGAL).
METHODS
Seventy-nine patients with acute ischemic stroke and 151 controls without vascular disease from a single German center were enrolled. A neurologist and a neuroradiologist ascertained clinical and radiological features. PLA and platelet activation were analyzed using flow cytometry with various antibodies. Coding as well as tagging SNPs in six genes determining PLA were genotyped. Three groups of parameters were correlated with each other: (i) clinical and radiological parameters, (ii) laboratory parameters, (iii) genetic parameters. For the comparisons, robust nonparametric statistical tests were applicable.
RESULTS
PLA and platelet activation were higher in ischemic stroke patients compared to controls. Both, anticoagulant and antiplatelet treatment in the patient group affected platelet activation but not PLA. PLA correlated weakly with measures of stroke severity but not with thrombus length or stroke etiology. The association of SNP rs2228315 in the P-Selectin Glycoprotein Ligand-1-gene (PSGL1) with ischemic stroke and platelet activation was significant before correction for multiple testing while a trend was observed for the association with PLA. Regression analysis revealed that (i) platelet activation was an independent determinant of stroke, (ii) that PLA correlated with stroke, sex, age and platelet activation and (iii) that platelet activation correlated only with stroke. None of the SNPs survived in the regression analysis for stroke, PLA or platelet activation as dependent variables.
CONCLUSIONS
The most important result of our study is that PLA and platelet activation are independent of other vascular risk factors correlated with stroke in our sample. In addition, we identified the missense SNP rs2228315 in the PSGL1-gene as a candidate polymorphism for ischemic stroke-related PLA. Association between this SNP and stroke as well as coronary artery disease has also been shown by two other studies.
Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Brain Ischemia; Female; Humans; Leukocytes; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Function Tests; Risk Factors; Stroke
PubMed: 25720421
DOI: 10.1159/000375396 -
Archives Des Maladies Du Coeur Et Des... Sep 2004Heart failure is a highly prevalent disease in aging western populations, associated with a substantially increased risk of thromboembolic events, not only in severe but... (Review)
Review
Heart failure is a highly prevalent disease in aging western populations, associated with a substantially increased risk of thromboembolic events, not only in severe but even in mild to moderate stages. This can partly be attributed to concomitant atrial fibrillation, a well-known risk factor for stroke, as well as a "hypercoagulable state" including formation of intraventricular thrombi. Left ventricular dysfunction results in decreased cardiac output, pulmonary congestion and neurohumoral activation with marked stimulation of the renin-angiotensin-aldosterone system. Besides its contribution to progressive left ventricular remodelling, activation of the renin-angiotensin-aldosterone system is enhanced in the development of vascular endothelial dysfunction in heart failure, resulting in decreased nitric oxide bioavailability. Nitric oxide, however, controls vascular tone and inhibits platelet activation. Enhanced platelet activation has recently been described in patients with heart failure in sinus rhythm. This article summarises the potential contribution to platelet activation of vascular endothelial dysfunction and reduced formation of the platelet inhibitor nitric oxide, which increase further the risk for thromboembolic events in heart failure. Beneficial modulation of cardiac remodelling, left ventricular function, neurohumoral activation, endothelial dysfunction and platelet activation can be achieved by inhibition of the renin-angiotensin-aldosterone system.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anticoagulants; Endothelium, Vascular; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Nitric Oxide; Platelet Activation; Platelet Aggregation Inhibitors; Renin-Angiotensin System; Thromboembolism
PubMed: 15521482
DOI: No ID Found