The Birth and Death of Platelets in Health and Disease

Pluthero, Fred G.; Kahr, Walter H A

doi:10.1152/physiol.00005.2018

Cited by 13 publications

(4 citation statements)

References 110 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, free TPO is degraded with rate γ x , and γ y is the rate of consumption of platelets that is assumed to be the same irrespective of whether it's bound or unbound to TPO. Here 1/γ y is average lifespan of an individual platelet that has been measured to be ≈ 1 week in humans [47]- [49].…”

Section: Deterministic Model Formulationmentioning

confidence: 99%

Dynamic analysis of sequestration-based feedbacks in cellular and biomolecular circuits

Dey

Vargas-García

Singh

2022

Preprint

View full text Add to dashboard Cite

Nonlinear feedback controllers are ubiquitous features of biological systems at different scales. A key motif arising in these systems is a sequestration-based feedback. As a physiological example of this type of feedback architecture, platelets (specialized cells involved in blood clotting) differentiate from stem cells, and this process is activated by a protein called Thrombopoietin (TPO). Platelets actively sequester and degrade TPO, creating negative feedback whereby any depletion of platelets increases the levels of freely available TPO that upregulates platelet production. We show similar examples of sequestration-based feedback in intracellular biomolecular circuits involved in heat-shock response and microRNA regulation. Our systematic analysis of this feedback motif reveals that platelets induced degradation of TPO is critical in enhancing system robustness to external disturbances. In contrast, reversible sequestration of TPO without degradation results in poor robustness to disturbances. We develop exact analytical results quantifying the limits to which the sensitivity to disturbances can be attenuated by sequestration-based feedback. Next, we consider the stochastic formulation of the circuit that takes into account low-copy number fluctuations in feedback components. Interestingly, our results show that the extent of random fluctuations are enhanced with increasing feedback strength, but can exhibit local maxima and minima across parameter regimes. In summary, our systematic analysis highlights design principles for enhancing the robustness of sequestration-based feedback mechanisms to external disturbances and inherent noise in molecular counts.

show abstract

Section: Deterministic Model Formulationmentioning

confidence: 99%

Dynamic analysis of sequestration-based feedbacks in cellular and biomolecular circuits

Dey

Vargas-García

Singh

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Platelets are small anuclear cells with a short half-life of 10 days derived from megakaryocytes [ 16 ]. Platelets have a uniform discoid shape, a complex intracellular structure with a cytoskeleton maintained by dynamic action, can synthesize proteins, are capable of dividing, and can respond to various stimuli with shape change, adhesion, aggregation as well as exposure of phosphatidylserine on the surface to induce clot formation and hemostasis [ 17 , 18 , 19 ].…”

Section: Platelet Physiologymentioning

confidence: 99%

Platelet-Therapeutics to Improve Tissue Regeneration and Wound Healing—Physiological Background and Methods of Preparation

et al. 2021

View full text Add to dashboard Cite

Besides their function in primary hemostasis, platelets are critically involved in the physiological steps leading to wound healing and tissue repair. For this purpose, platelets have a complex set of receptors allowing the recognition, binding, and manipulation of extracellular structures and the detection of pathogens and tissue damage. Intracellular vesicles contain a huge set of mediators that can be released to the extracellular space to coordinate the action of platelets as other cell types for tissue repair. Therapeutically, the most frequent use of platelets is the intravenous application of platelet concentrates in case of thrombocytopenia or thrombocytopathy. However, there is increasing evidence that the local application of platelet-rich concentrates and platelet-rich fibrin can improve wound healing and tissue repair in various settings in medicine and dentistry. For the therapeutic use of platelets in wound healing, several preparations are available in clinical practice. In the present study we discuss the physiology and the cellular mechanisms of platelets in hemostasis and wound repair, the methods used for the preparation of platelet-rich concentrates and platelet-rich fibrin, and highlight some examples of the therapeutic use in medicine and dentistry.

show abstract

“…Their primary function is regulating hemostasis and thrombosis [ 58 ], although more recently they have been shown to play important roles in inflammation [ 59 ]. However, there is a delicate balance between the physiological and pathophysiological role of platelets due to their mediation of complex vascular responses in innate and adaptive immunity [ 60 ]. Therefore, over the years the pathophysiologic role of platelets has been studied extensively in thrombotic disorders such as myocardial infarction (MI), IS, and venous thromboembolism.…”

Section: Platelets In Strokementioning

confidence: 99%

Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology

Ansari

Gavins

2021

Biomedicines

View full text Add to dashboard Cite

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.

show abstract

The Birth and Death of Platelets in Health and Disease

Cited by 13 publications

References 110 publications

Dynamic analysis of sequestration-based feedbacks in cellular and biomolecular circuits

Dynamic analysis of sequestration-based feedbacks in cellular and biomolecular circuits

Platelet-Therapeutics to Improve Tissue Regeneration and Wound Healing—Physiological Background and Methods of Preparation

Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology

Contact Info

Product

Resources

About