Plasma fibronectin supports hemostasis and regulates thrombosis

Wang, Yiming; Adili, Reheman; Spring, Christopher M.; Kalantari, Jalil; Marshall, Alexandra H.; Wolberg, Alisa S.; Gross, Peter L.; Weitz, Jeffrey I.; Rand, Margaret L.; Mosher, Deane F.; Freedman, John; Ni, Heyu

doi:10.1172/jci74630

Cited by 156 publications

(163 citation statements)

References 59 publications

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“…In addition, we demonstrate that platelet-derived TSP1, but not endothelial-derived TSP1, modulates arterial thrombosis in vivo. The multidomain structure of TSP1 allows it to interact with many proteins including collagen, VWF, fibrinogen, and fibronectin, all of which have been shown to be mediating platelet recruitment to subendothelial matrix after injury to the arterial wall, 31,[33][34][35][36][37][38] suggesting that TSP1 may contribute to initial platelet adhesion. However, the evidence to support the role of TSP1 in platelet adhesion to the injured vessel wall is not well elucidated and remains debatable.…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Prakash

Kulkarni

Chauhan

2015

Blood

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Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Prakash

Kulkarni

Chauhan

2015

Blood

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“…To assess the effects of exenatide on a metric that depends on both platelet function and coagulation in vivo, murine tail bleeding assays were also performed (31,32). Mice were given a single injection of exenatide (60 nmol/L/kg i.v.…”

Section: Tail Bleeding Timementioning

confidence: 99%

Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis

et al. 2016

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Short-term studies in subjects with diabetes receiving glucagon-like peptide 1 (GLP-1)-targeted therapies have suggested a reduced number of cardiovascular events. The mechanisms underlying this unexpectedly rapid effect are not known. We cloned full-length GLP-1 receptor (GLP-1R) mRNA from a human megakaryocyte cell line (MEG-01), and found expression levels of GLP-1Rs in MEG-01 cells to be higher than those in the human lung but lower than in the human pancreas. Incubation with GLP-1 and the GLP-1R agonist exenatide elicited a cAMP response in MEG-01 cells, and exenatide significantly inhibited thrombin-, ADP-, and collagen-induced platelet aggregation. Incubation with exenatide also inhibited thrombus formation under flow conditions in ex vivo perfusion chambers using human and mouse whole blood. In a mouse cremaster artery laser injury model, a single intravenous injection of exenatide inhibited thrombus formation in normoglycemic and hyperglycemic mice in vivo. Thrombus formation was greater in mice transplanted with bone marrow lacking a functional GLP-1R (Glp1r 2/2 ), compared with those receiving wild-type bone marrow. Although antithrombotic effects of exenatide were partly lost in mice transplanted with bone marrow from Glp1r 2/2 mice, they were undetectable in mice with a genetic deficiency of endothelial nitric oxide synthase. The inhibition of platelet function and the prevention of thrombus formation by GLP-1R agonists represent potential mechanisms for reduced atherothrombotic events.Type 2 diabetes (T2D) is associated with a number of risk factors that contribute to an increased risk of atherothrombotic events, including hypertension, dyslipidemia, obesity, and chronic inflammation, as well as endothelial and platelet dysfunction (1). Platelets are small, versatile, anucleate cells in the circulation that play critical roles in both early and late stages of atherothrombosis, contributing also to cell-based thrombin generation and blood coagulation (2). Subjects with T2D exhibit a prothrombotic state, including increased production of coagulation factors; decreased production of fibrinolytic factors; and a propensity to platelet activation, aggregation, and adhesion (1,3,4). Compounding the latter, subjects with T2D show reduced sensitivity to antiplatelet drugs, such as aspirin and clopidogrel (5,6), and manifest a higher incidence of cardiovascular events (1,6,7). Although the currently available antidiabetic agents have been effective at lowering blood glucose levels and preventing microvascular disease, until the recent EMPA-REG study (8), it had been exceedingly difficult to demonstrate the beneficial effects of normalizing blood glucose

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“…The recently described concept of a "protein wave of haemostasis" may indicate a potential role of platelet-released plasma fibronectin in thrombosis and haemostasis mechanisms (26). Moreover, platelets are key mediators of atherothrombosis, which are actively involved in all three waves of thrombus formation (27): (I) protein wave; (II) platelet accretion; and (III) blood coagulation.…”

Section: Platelet Receptors As Therapeutic Targetsmentioning

confidence: 99%

Platelets: an outlook from biology through evidence-based achievements in critical care

Costa-Filho

Bozza

2017

Ann. Transl. Med.

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Since the original observations by Bizzozero and Osler, we have seen tremendous advances in the understanding of platelets far beyond haemostasis and the restoration of injured endothelium. In this minireview on platelets, we will briefly outline their historical description and the importance of their evolution, focusing on a 450 million years old living fossil of Limulus polyphemus, a marine chelicerate arthropod, which helped researchers explain the basis for the immunity role of platelets and make correlations with platelet ultrastructure and function. In addition, the impact of the Limulus Amoebocyte Lysate (LAL) test for modern medicine is highlighted. The role of platelets in cardiovascular diseases, their relevance in arterial and venous thrombosis, and the utilization of antithrombotic drugs as therapeutic agents are also reported.Furthermore, platelet receptors are crucial in aggravating or mitigating other diseases, such as cancer and infections, which can recruit cells and have numerous interactions in a process recently coined "NETosis formation", which is also briefly depicted.

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Plasma fibronectin supports hemostasis and regulates thrombosis

Cited by 156 publications

References 59 publications

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis

Platelets: an outlook from biology through evidence-based achievements in critical care

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