Aquaporin-1 regulates platelet procoagulant membrane dynamics and in vivo thrombosis

Agbani, Ejaife O.; Williams, Christopher M.; Li, Yong; Bosch, Marion van den; Moore, Samantha; Mauroux, Adele; Hodgson, Lorna; Hers, Ingeborg; Poole, Alastair W.

doi:10.1172/jci.insight.99062

Cited by 32 publications

(58 citation statements)

References 60 publications

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“…Our results are consistent with the previous report showing that platelets from children with a mutation of AQP7 have impaired ATP secretion from dense granules (Goubau et al, 2013). In the very recently published paper, Agbani et al demonstrated that platelets from AQP1 knockout mice have only slightly impaired secretion from the dense granules (Agbani et al, 2018). This was interpreted to mean that AQP1 is not directly involved in the platelet secretory response.…”

Section: Discussionsupporting

confidence: 93%

“…The results presented here suggest that besides recently discovered AQP1 (Agbani et al, 2018) and AQP7 (Goubau et al, 2013), human platelets are likely to possess ten additional subtypes of AQP family members belonging to the subfamilies of classical aquaporins (AQPs 0-2 and AQPs 4-6), aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) and superaquaporins (AQP11 and 12) (Fig. 1A).…”

Section: Discussionsupporting

confidence: 53%

“…A study performed on platelets from three children with a mutation of the AQP7 gene indicated that human platelets possess AQP7 and that this AQP isoform may be important for platelet morphology, aggregation (adrenaline-induced), and secretion (Goubau et al, 2013). A more recent study also revealed presence of AQP1 in human platelets (Agbani et al, 2018). Using AQP1-null mice it was shown that this AQP isoform is crucial for the platelet procoagulant response.…”

Section: Introductionmentioning

confidence: 99%

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Aquaporins in human platelets: intracellular localization and possible role in granule and lysosome secretion

Misztal¹,

Rusak²,

Brańska-Januszewska³

et al. 2018

Acta Biochim Pol

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This study was undertaken to establish the presence and the role of aquaporins (AQPs) in human platelets. Immunodetection with polyclonal antibodies and fluorescent microscopy suggest the presence of AQP isoforms – 0–7 and 9–12 – localized (in resting platelets) in the plasma membrane and in the dense and alpha granules. In thrombin- or monensin-treated platelets, the granules’ AQPs become visible in the whole cell body, indicating the granules’ swelling. In our studies on the role of AQPs in platelet responses we used tetrachloroauric acid (HAuCl4), a classical water channel blocker. We found that 10–100 µM of Au(III) inhibited the hypotonicity-, monensin (simulating the action of Na+/H+ exchanger)-, and collagen-evoked platelet swelling and reduced tritiated water uptake by platelets treated by collagen or monensin, indicating its ability to block water channels in these cells. HAuCl4, at the concentrations reducing water influx, did not induce cell lysis, alter the plasma membrane shape or the –SH group content. The inhibitor also failed to affect Na+ and Cl--related osmotic gradient formation and protein kinase D2 phosphorylation. In platelets activated by threshold concentrations of collagen, the thrombin receptor activating peptide, ADP, calcium ionophore A23187, phorbol ester and arachidonic acid, HAuCl4 (100 µM) completely inhibited secretion of ATP from dense granules but failed to reduce platelet aggregation. In collagen-stimulated platelets, HAuCl4 (10–100 µM) reduced secretion from dense and alpha granules, as well as lysosomes, in a dose-dependent manner. We conclude that human platelets possess numerous AQPs subtypes localized in the plasma and granule membranes. AQP-mediated water fluxes may be crucial for platelet volume regulation as well as secretion from dense and alpha granules and lysosomes.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aquaporins in human platelets: intracellular localization and possible role in granule and lysosome secretion

Misztal¹,

Rusak²,

Brańska-Januszewska³

et al. 2018

Acta Biochim Pol

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“…Intriguingly, treatment of platelets with Au(III) did not affect the generation of a calcium signal in thrombin-or collagen-activated platelets notably (Figure 11), a well-accepted prerequisite for the development of platelet procoagulant response (Varga-Szabo et al, 2009;Obydennyy et al, 2016). Our observation is contrary to those obtained by Agbani et al (2018), where authors observed diminished calcium signal in platelets from AQP1-null mice adhered to collagen. Possible explanation To investigate effect of HAuCl 4 on platelet ballooning, platelets (in whole blood) preincubated without (−Au) or with (+Au) HAuCl 4 (100 μM) were allowed to adhere to a collagen-coated surface under shear rate of 1,000 s −1 , followed by 4 min staining with Alexa Fluor 647-ANX V (1:200).…”

Section: Engagement Of Aqps In Platelet Procoagulant Responsecontrasting

confidence: 97%

HAuCl4, Putative General Aquaporins Blocker, Reduces Platelet Spreading, Filopodia Formation, Procoagulant Response, and Thrombus Formation Under Flow

et al. 2020

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Background: Recent studies indicate that aquaporin (AQP) water channels have a regulatory function in human platelet secretion and in procoagulant response of murine platelets. However, the engagement of AQPs in morphological changes, procoagulant response, and thrombus formation in human blood has never been investigated. Methods: Confocal microscopy was used to study platelet spreading, filopodia formation, ballooning, and thrombus formation under flow. Flow cytometry was utilized to assess platelet phosphatidylserine (PS) exposure and microparticles shedding. Kinetics of clot formation in vitro was evaluated by thromboelastometry. Mouse model of ferric chloride (III) (FeCl 3)-induced thrombosis was used to investigate thrombus formation in vivo. Results: We found that chloroauric(III) acid (HAuCl 4), a classical AQP inhibitor (10-100 μM), reduced spreading of human platelets on collagen-coated surfaces and inhibited filopodia formation in a fluid phase. Under flow conditions, HAuCl 4 (100 μM) attenuated thrombi growth on collagen, platelet secretion, and PS exposure. Thrombus formation was restored by the addition of exogenous adenosine diphosphate (ADP). Collagen-evoked platelet procoagulant response (evaluated as PS exposure, shedding of microparticles, plateletdependent thrombin generation, and membrane ballooning) was distinctly reduced by HAuCl 4 (25-200 μM), as well as the dynamics of clot formation. In mouse model of thrombosis, reduction of surface of PS-positive cells within thrombus was observed in the presence of HAuCl 4 (1-10 mg/kg). Conclusion: These results suggest that in human platelets AQPs are crucial for agonistevoked morphological changes, thrombus formation under flow, and in development of procoagulant response. Antithrombotic effect in vivo suggests that nontoxic inhibitors of AQPs may be considered as potential candidates for a novel class of antiplatelet drugs.

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“…Alternatively, mitochondrial depolarization (70), scramblase activity (146,147), or water entry into platelets (33,148) are potential targets to inhibit formation of the thrombin-generating subpopulation of platelets while still allowing platelet aggregation to occur. It may be that inhibition of procoagulant platelet formation could be an alternative approach to reduce thrombosis without impairing hemostasis.…”

Section: Conclusion: Potential Of Procoagulant Phosphatidylserine-expmentioning

confidence: 99%

Procoagulant Phosphatidylserine-Exposing Platelets in vitro and in vivo

Reddy

Rand

2020

Front. Cardiovasc. Med.

112

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The physiological heterogeneity of platelets leads to diverse responses and the formation of discrete subpopulations upon platelet stimulation. Procoagulant platelets are an example of such subpopulations, a key characteristic of which is exposure either of the anionic aminophospholipid phosphatidylserine (PS) or of tissue factor on the activated platelet surface. This review focuses on the former, in which PS exposure on a subpopulation of platelets facilitates assembly of the intrinsic tenase and prothrombinase complexes, thereby accelerating thrombin generation on the activated platelet surface, contributing importantly to the hemostatic process. Mechanisms involved in platelet PS exposure, and accompanying events, induced by physiologically relevant agonists are considered then contrasted with PS exposure resulting from intrinsic pathway-mediated apoptosis in platelets. Pathologies of PS exposure, both inherited and acquired, are described. A consideration of platelet PS exposure as an antithrombotic target concludes the review.

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Aquaporin-1 regulates platelet procoagulant membrane dynamics and in vivo thrombosis

Cited by 32 publications

References 60 publications

Aquaporins in human platelets: intracellular localization and possible role in granule and lysosome secretion

Aquaporins in human platelets: intracellular localization and possible role in granule and lysosome secretion

HAuCl4, Putative General Aquaporins Blocker, Reduces Platelet Spreading, Filopodia Formation, Procoagulant Response, and Thrombus Formation Under Flow

Procoagulant Phosphatidylserine-Exposing Platelets in vitro and in vivo

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