Endogenous hepoxilin A3, produced under short duration of high shear-stress, inhibits thrombin-induced aggregation in human platelets

1994 ◽  
Vol 1190 (1) ◽  
pp. 173-176 ◽  
Author(s):  
Alon Margalit ◽  
Yosef Granot
Keyword(s):  
Shear Stress ◽  
Short Duration ◽  
Human Platelets ◽  
High Shear ◽  
High Shear Stress ◽  
Induced Aggregation ◽  
Hepoxilin A3

scholarly journals Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation

2019 ◽  
Vol 20 (20) ◽  
pp. 5040 ◽  
Author(s):  
Thien Ngo ◽  
Keunyoung Kim ◽  
Yiying Bian ◽  
Hakjun Noh ◽  
Kyung-Min Lim ◽  
...  
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Ex Vivo ◽  
Antiplatelet Agents ◽  
Human Platelets ◽  
Platelet Glycoprotein ◽  
High Shear ◽  
High Shear Stress ◽  
Paeonia Suffruticosa ◽  
Induced Aggregation

Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agents selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets. The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented arterial thrombosis in vivo from the dose of 10 mg/kg without prolonging bleeding time or blood clotting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile.

Effect of a New Monoclonal Anti-Glycoprotein IX Antibody, KMP-9, on High Shear-Induced Platelet Aggregation

1997 ◽  
Vol 78 (02) ◽  
pp. 902-909 ◽  
Author(s):  
Tetsuya Miyake ◽  
Shosaku Nomura ◽  
Yutaka Komiyama ◽  
Yasuhiko Miyazaki ◽  
Hideo Kagawa ◽  
...  
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Platelet Glycoprotein ◽  
High Shear ◽  
High Shear Stress ◽  
Receptor Component ◽  
Induced Aggregation

SummaryHuman platelet glycoprotein Ib/IX complex acts as a receptor for von Willebrand factor. It is widely accepted that glycoprotein lb is the essential receptor component, but the role of glycoprotein IX is still unclear. We produced a new monoclonal anti-glycoprotein IX antibody (KMP-9) by the hybridoma technique using platelets from a patient with Glanzmann’s thrombasthenia. The epitope of KMP-9 was localized to the C-terminal 8 kD fragment of glycoprotein IX using ELISA analysis of polyethylene-pin-synthesized peptides, as well as Western blot analysis of platelets after digestion with N-glycosidase and Staphylococcus aureus V8 protease. KMP-9 partially inhibited high shear stress-induced platelet aggregation, but had no effect on aggregation induced by ristocetin or low shear stress. Its inhibitory effect on high shear stress-induced aggregation was weaker than that of antiglycoprotein lb or anti-glycoprotein Ilb/IIIa monoclonal antibodies. A 21-mer synthetic peptide (glycoprotein IX L110-G130) inhibited the binding of KMP-9 to platelets. It also competively inhibited the suppression of high shear stress-induced platelet aggregation by KMP-9, but had no direct effect on this aggregation. KMP-9 may be useful to clarify the physiological role of GPIX.

Intermittent short-duration exposure to low wall shear stress induces intimal thickening in arteries exposed to chronic high shear stress

2006 ◽  
Vol 80 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Hiroshi Nanjo ◽  
Eiketsu Sho ◽  
Masayo Komatsu ◽  
Mien Sho ◽  
Christopher K. Zarins ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Short Duration ◽  
High Shear ◽  
Intimal Thickening ◽  
High Shear Stress ◽  
Wall Shear

Pathologic high shear stress induces apoptosis events in human platelets

2004 ◽  
Vol 320 (2) ◽  
pp. 303-310 ◽  
Author(s):  
Valery Leytin ◽  
David J. Allen ◽  
Sergiy Mykhaylov ◽  
Lukasz Mis ◽  
Elena V. Lyubimov ◽  
...  
Keyword(s):  
Shear Stress ◽  
Human Platelets ◽  
High Shear ◽  
High Shear Stress

scholarly journals 5065Platelet desialylation induced by high shear-stress mechanical circulatory support

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
H Spillemaeker ◽  
A Dupont ◽  
A Kauskot ◽  
A Rauch ◽  
F Vincent ◽  
...  
Keyword(s):  
Shear Stress ◽  
Mechanical Circulatory Support ◽  
Circulatory Support ◽  
High Shear ◽  
High Shear Stress

scholarly journals Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1354-1361 ◽  
Author(s):  
JR O'Brien ◽  
GP Salmon
Keyword(s):  
Shear Stress ◽  
Bleeding Time ◽  
Platelet Rich Plasma ◽  
Divalent Cations ◽  
Mean Transit Time ◽  
Platelet Glycoprotein ◽  
High Shear ◽  
The Difference ◽  
Von Willebrand’S Factor ◽  
Induced Aggregation

The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of “membrane-active” drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin- induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.

scholarly journals Nitric Oxide–Dependent and Nitric Oxide–Independent Transcriptional Responses to High Shear Stress in Endothelial Cells

Hypertension ◽  
2005 ◽  
Vol 45 (4) ◽  
pp. 672-680 ◽  
Author(s):  
Branko Braam ◽  
Remmert de Roos ◽  
Hans Bluyssen ◽  
Patrick Kemmeren ◽  
Frank Holstege ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
High Shear ◽  
High Shear Stress ◽  
Transcriptional Responses
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