Phosphatidylinositol 4,5-Bisphosphate Regulates Activation-Induced Platelet Microparticle Formation†

Biochemistry ◽  
2005 ◽  
Vol 44 (16) ◽  
pp. 6361-6370 ◽  
Author(s):  
Daniel J. O'Connell ◽  
Nataliya Rozenvayn ◽  
Robert Flaumenhaft
Keyword(s):  
Microparticle Formation

scholarly journals Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

Toxics ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 33
Author(s):  
Po-Ching Chu ◽  
Charlene Wu ◽  
Ta-Chen Su
Keyword(s):  
Young Adults ◽  
Endothelial Dysfunction ◽  
Vascular Diseases ◽  
Adolescents And Young Adults ◽  
Cardiovascular Risks ◽  
Phthalate Exposure ◽  
Butyl Phthalate ◽  
Microparticle Formation

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

scholarly journals Mitochondrial Inner Membrane Depolarization as a Marker of Platelet Apoptosis

2016 ◽  
Vol 23 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Armen V. Gyulkhandanyan ◽  
David J. Allen ◽  
Sergiy Mykhaylov ◽  
Elena Lyubimov ◽  
Heyu Ni ◽  
...  
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Calcium Ionophore ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Calcium Ionophore A23187 ◽  
Clinical Settings ◽  
Ionophore A23187 ◽  
Platelet Apoptosis ◽  
Mitochondrial Inner Membrane ◽  
Microparticle Formation

Availability of universal marker for the diagnosis of platelet apoptosis is an important but currently unresolved goal of platelet physiology investigations. Mitochondrial inner transmembrane potential (▵Ψm) depolarization is frequently used as a marker of apoptosis in nucleated cells and anucleate platelets. Since ▵Ψm depolarization in platelets is also frequently associated with concurrent induction of other apoptotic responses, it may appear that ▵Ψm depolarization is a good universal marker of platelet apoptosis. However, data presented in the current study indicate that this is incorrect. We report here fundamental differences in the effects of potassium ionophore valinomycin and calcium ionophore A23187 on human platelet apoptosis. Although both A23187-triggered and valinomycin-triggered ▵Ψm depolarization are strongly induced, the former is dependent on the opening of mitochondrial permeability transition pore (MPTP) and the latter is MPTP-independent. Furthermore, effects of calcium and potassium ionophores on other apoptotic events are also basically different. A23187 induces caspase-3 activation, proapoptotic Bax and Bak protein expression, phosphatidylserine exposure, and microparticle formation, whereas valinomycin does not induce these apoptotic manifestations. Discovery of targeted ▵Ψm depolarization not associated with apoptosis in valinomycin-treated platelets indicates that this marker should not be used as a single universal marker of platelet apoptosis in unknown experimental and clinical settings as it may lead to a false-positive apoptosis diagnosis.

Activated Platelets Enhance Microparticle Formation and Platelet-Leukocyte Interaction in Severe Trauma and Sepsis

2001 ◽  
Vol 50 (5) ◽  
pp. 801-809 ◽  
Author(s):  
Hiroshi Ogura ◽  
Tomio Kawasaki ◽  
Hiroshi Tanaka ◽  
Taichin Koh ◽  
Reiichirou Tanaka ◽  
...  
Keyword(s):  
Severe Trauma ◽  
Activated Platelets ◽  
Microparticle Formation

Platelet P-selectin facilitates atherosclerotic lesion development

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2661-2666 ◽  
Author(s):  
Peter C. Burger ◽  
Denisa D. Wagner
Keyword(s):  
Atherosclerotic Lesion ◽  
Soluble Form ◽  
Wild Type ◽  
Lesion Development ◽  
Atherosclerotic Lesions ◽  
Lesion Growth ◽  
Microparticle Formation ◽  
Apoe Deficient Mouse ◽  
Atherosclerotic Lesion Development

P-selectin is an adhesion molecule expressed on activated platelets and endothelium. It is known to play an important role in atherosclerosis. P-selectin also circulates in plasma in a soluble form (sP-selectin), which induces procoagulant microparticle formation. We investigated the role of platelet versus endothelial P-selectin in generating sP-selectin and in the formation of atherosclerotic lesions in the apolipoprotein E (apoE)–deficient mouse model. For this we transplanted apoE−/−P-selectin−/− and apoE−/−P-selectin+/+ lethally irradiated mice with bone marrow of either genotype. Seven months after transplantation, we determined from the chimeric animals that the majority of circulating sP-selectin was of endothelial origin. Thus, in atherosclerosis, the procoagulant sP-selectin reflects endothelial rather than platelet activation. We found that endothelial P-selectin was crucial for the promotion of atherosclerotic lesion growth because in its absence only relatively small lesions developed. However, platelet P-selectin also contributed to the lesion development because lesions in wild-type recipients receiving transplants with wild-type platelets were 30% larger than those receiving P-selectin-deficient platelets (P < .008) and were more frequently calcified (80% versus 44%). In comparison with P-selectin wild-type animals, absence of either endothelial or platelet P-selectin inhibited migration of smooth muscle cells into the lesion. Thus, in addition to endothelium, platelets and their P-selectin also actively promote advanced atherosclerotic lesion development.

OS 02-03 EFFECT OF HIGH GLUCOSE EXPOSURE ON ENDOTHELIAL MICROPARTICLE FORMATION AND COMPOSITION

2016 ◽  
Vol 34 (Supplement 1) ◽  
pp. e48 ◽  
Author(s):  
Maddison Turner ◽  
Larissa Reid ◽  
Mercedes Munkonda ◽  
Dylan Burger
Keyword(s):  
High Glucose ◽  
Glucose Exposure ◽  
Microparticle Formation

Platelet microparticle formation and thrombin generation under high shear are effectively suppressed by a monoclonal antibody against GPIbα

2006 ◽  
Vol 96 (12) ◽  
pp. 774-780 ◽  
Author(s):  
Luca Pontiggia ◽  
Beat Steiner ◽  
Hans Ulrichts ◽  
Hans Deckmyn ◽  
Marc Forestier ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Thrombin Generation ◽  
Platelet Rich Plasma ◽  
Annexin V ◽  
High Shear ◽  
Double Labeling ◽  
Platelet Aggregometry ◽  
Microparticle Formation ◽  
Arterial Stenoses ◽  
Von Willebrand

SummaryWe studied the inhibition of platelet microparticle (MP) formation and thrombin generation under high shear forces. We hypothesized that an inhibitor of the GPIbα-von Willebrand factor (vWF) interaction would be more effective in suppressing MP formation and thrombin generation than GPIIb/IIIa inhibitors. Platelet-rich plasma (PRP) anticoagulated with PPACK (D-Phe-Pro-Arg chloromethyl ketone) was exposed in a coneand-plate viscometer (shear: 5,000 s−1 for5 min) in the presence of antagonists to GPIbα (the monoclonal antibody [Mab] Ib-23) or to GPIIb/IIIa (abciximab, tirofiban, eptifibatide) at their IC90 determined in platelet aggregometry with ristocetin or ADP, respectively. We used double labeling (CD41-PE and annexin-V-FITC) for flow cytometric detection of MP and their aminophospholipid exposure. Thrombin generation was measured using PRP prepared fromACD anticoagulated blood. About 40% of the thrombin generation was found to be mediated by the MP fraction of the PRP. Blockade of GPIbα with Mab Ib-23 reduced MP formation and thrombin generation by 50%, and was more effective than any GPIIb/IIIa antagonist. The combination of Mab Ib-23 with one of the GPIIb/IIIa inhibitors further reduced the MP formation to ∼30%. The antibody also partially inhibited thrombin induced platelet aggregation. Epitope mapping suggested that Mab Ib-23 binds between the amino acids 201 and 268 of GPIbα, explaining the interference with vWF and thrombin interaction. In contrast to the commonly used GPIIb/IIIa antagonists, the blockade of GPIbα with Mab Ib-23 effectively reduces the prothrombotic MP generation and thrombin formation at shear rates typically found in arterial stenoses.

scholarly journals Microparticle Formation in Peritoneal Dialysis

2017 ◽  
Vol 4 ◽  
pp. 205435811769982 ◽  
Author(s):  
Shareef Akbari ◽  
Rima Abou-Arkoub ◽  
Suzy Sun ◽  
Swapnil Hiremath ◽  
Arkadiy Reunov ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Microparticle Formation

scholarly journals Microparticle formation by platelets exposed to high gas pressures – An oxidative stress response

2016 ◽  
Vol 101 ◽  
pp. 154-162 ◽  
Author(s):  
Jasjeet Bhullar ◽  
Veena M. Bhopale ◽  
Ming Yang ◽  
Kinjal Sethuraman ◽  
Stephen R. Thom
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Microparticle Formation ◽  
Gas Pressures
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