The platelet shape change: biophysical basis and physiological consequences

Moskalensky, Alexander E.; Litvinenko, Alena L.

doi:10.1080/09537104.2018.1514109

Cited by 19 publications

(24 citation statements)

References 58 publications

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“…The adhesion of platelets to sub-endothelial matrix proteins leads to platelet intracellular signaling, which activates the cell. Briefly, platelet activation results in conformational change (from the typical discoid shape to an elongated form) (11) and degranulation (i.e., release of the platelet cytoplasmic granules content) (12). α-granules release VWF and coagulation factors, such as fibrinogen, factor V, factor XIII, and P-selectin (also expressed on the platelet surface following activation); Dense granules release platelets agonists, such as serotonin and adenosine diphosphate (ADP) (13).…”

Section: The Traditional Biochemical Cascade Of Thrombosismentioning

confidence: 99%

Shear-Dependent Platelet Aggregation: Mechanisms and Therapeutic Opportunities

Rana

Westein

Niego

et al. 2019

Front. Cardiovasc. Med.

129

117

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Cardiovascular diseases (CVD) are the number one cause of morbidity and death worldwide. As estimated by the WHO, the global death rate from CVD is 31% wherein, a staggering 85% results from stroke and myocardial infarction. Platelets, one of the key components of thrombi, have been well-investigated over decades for their pivotal role in thrombus development in healthy as well as diseased blood vessels. In hemostasis, when a vascular injury occurs, circulating platelets are arrested at the site of damage, where they are activated and aggregate to form hemostatic thrombi, thus preventing further bleeding. However, in thrombosis, pathological activation of platelets occurs, leading to uncontrolled growth of a thrombus, which in turn can occlude the blood vessel or embolize, causing downstream ischemic events. The molecular processes causing pathological thrombus development are in large similar to the processes controlling physiological thrombus formation. The biggest challenge of anti-thrombotics and anti-platelet therapeutics has been to decouple the pathological platelet response from the physiological one. Currently, marketed anti-platelet drugs are associated with major bleeding complications for this exact reason; they are not effective in targeting pathological thrombi without interfering with normal hemostasis. Recent studies have emphasized the importance of shear forces generated from blood flow, that primarily drive platelet activation and aggregation in thrombosis. Local shear stresses in obstructed blood vessels can be higher by up to two orders of magnitude as compared to healthy vessels. Leveraging abnormal shear forces in the thrombus microenvironment may allow to differentiate between thrombosis and hemostasis and develop shear-selective anti-platelet therapies. In this review, we discuss the influence of shear forces on thrombosis and the underlying mechanisms of shear-induced platelet activation. Later, we summarize the therapeutic approaches to target shear-sensitive platelet activation and pathological thrombus growth, with a particular focus on the shear-sensitive protein von Willebrand Factor (VWF). Inhibition of shear-specific platelet aggregation and targeted drug delivery may prove to be much safer and efficacious approaches over current state-of-the-art antithrombotic drugs in the treatment of cardiovascular diseases.

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Section: The Traditional Biochemical Cascade Of Thrombosismentioning

confidence: 99%

Shear-Dependent Platelet Aggregation: Mechanisms and Therapeutic Opportunities

Rana

Westein

Niego

et al. 2019

Front. Cardiovasc. Med.

129

117

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“…Important constituents of the contractile apparatus are the microtubules and actin filaments. The microtubules build an intracellular ring called the microtubule band, which is located in the equator region of the platelets [10]. The configuration is responsible for the disc shape of the resting platelets.…”

Section: The Contractile Apparatus Of Plateletsmentioning

confidence: 99%

Clot Retraction: Cellular Mechanisms and Inhibitors, Measuring Methods, and Clinical Implications

Jansen

Hartmann

2021

Biomedicines

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Platelets have important functions in hemostasis. Best investigated is the aggregation of platelets for primary hemostasis and their role as the surface for coagulation leading to fibrin- and clot-formation. Importantly, the function of platelets does not end with clot formation. Instead, platelets are responsible for clot retraction through the concerted action of the activated αIIbβ3 receptors on the surface of filopodia and the platelet’s contractile apparatus binding and pulling at the fibrin strands. Meanwhile, the signal transduction events leading to clot retraction have been investigated thoroughly, and several targets to inhibit clot retraction have been demonstrated. Clot retraction is a physiologically important mechanism allowing: (1) the close contact of platelets in primary hemostasis, easing platelet aggregation and intercellular communication, (2) the reduction of wound size, (3) the compaction of red blood cells to a polyhedrocyte infection-barrier, and (4) reperfusion in case of thrombosis. Several methods have been developed to measure clot retraction that have been based on either the measurement of clot volume or platelet forces. Concerning the importance of clot retraction in inborn diseases, the failure of clot retraction in Glanzmann thrombasthenia is characterized by a bleeding phenotype. Concerning acquired diseases, altered clot retraction has been demonstrated in patients with coronary heart disease, stroke, bronchial asthma, uremia, lupus erythematodes, and other diseases. However, more studies on the diagnostic and prognostic value of clot retraction with methods that have to be standardized are necessary.

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“…Upon platelet activation, a series of responses occurs, including changes in shape, aggregation, and the migration of granules to the cell surface that release various factors, such as platelet factor 4 (PF4), CD40 ligand, and adenosine diphosphate (ADP), etc. [ 8 , 9 ]. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in platelet activation that is induced by multiple stimulants.…”

Section: Introductionmentioning

confidence: 99%

Fruitflow inhibits platelet function by suppressing Akt/GSK3β, Syk/PLCγ2 and p38 MAPK phosphorylation in collagen-stimulated platelets

Chen

Zhang

Wang

et al. 2022

BMC Complement Med Ther

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Background Platelets play an important role in the progression of atherosclerosis and cardiovascular events. The inhibition of platelet function is a main strategy to reduce risk of cardiovascular events. Some studies have shown that tomato extracts inhibit platelet function, but the molecular mechanisms remain unclear. Fruitflow is a water-solute tomato extract and the main ingredients including flavonoids, adenosine, chlorogenic acid, phytosterols, naringenin, and carotenoids. The present study investigated the effects of fruitflow on adenosine diphosphate (ADP)- and collagen- stimulated platelet aggregation, platelet adhesion, and levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (PGF1α), and platelet factor 4 (PF4) and explored the underlying molecular mechanisms. Methods Platelet-rich plasma (PRP) was used for measurement of platelet aggregation, TXB2, 6-keto- PGF1α, and PF4 levels. Platelet aggregation was analyzed using a Chrono-Log aggregometer. TXB2, 6-keto- PGF1α, and PF4 levels were determined using enzyme-linked immunosorbent assay kits. Immunoblotting was used to detect protein expression and phosphorylation on washed platelets. Platelet adhesion and spreading were determined by immunofluorescence. Results Fruitflow (1, 3, 10 and 100 μg/ml) dose-dependently inhibited platelet aggregation that was induced by ADP and collagen. Fruitflow (100 μg/ml) treatment completely suppressed ADP- and collagen-stimulated platelet aggregation. Fruitflow (100 μg/ml) significantly decreased TXB2 and 6-keto-PGF1α generation and PF4 release in ADP- and collagen-stimulated platelets. Treatment with fruitflow effectively blocked collagen-induced platelet spreading. To determine the potential molecule mechanism of action of fruitflow, we investigated the protein expression and phosphorylation of several signaling molecules in collagen-activated platelets. Fruitflow dose-dependently suppressed Akt, Glycogen synthase kinase-3β (GSK-3β), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) and p38 MAPK phosphorylation that was induced by collagen. Conclusion Fruitflow inhibited platelet aggregation and reduced TXB2, 6-keto-PGF1α, and PF4 levels in ADP- and collagen-stimulated platelets. The mechanism of action of fruitflow may be associated with the suppression of Akt/GSK3β, Syk/PLCγ2, and p38 MAPK phosphorylation in collagen-activated platelets. Fruitflow is a natural product derived from tomato and can be used as a health food for decreasing platelet activity.

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The platelet shape change: biophysical basis and physiological consequences

Cited by 19 publications

References 58 publications

Shear-Dependent Platelet Aggregation: Mechanisms and Therapeutic Opportunities

Shear-Dependent Platelet Aggregation: Mechanisms and Therapeutic Opportunities

Clot Retraction: Cellular Mechanisms and Inhibitors, Measuring Methods, and Clinical Implications

Fruitflow inhibits platelet function by suppressing Akt/GSK3β, Syk/PLCγ2 and p38 MAPK phosphorylation in collagen-stimulated platelets

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