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

JCI Insight
Ejaife O AgbaniA W Poole

Abstract

In response to collagen stimulation, platelets use a coordinated system of fluid entry to undergo membrane ballooning, procoagulant spreading, and microvesiculation. We hypothesized that water entry was mediated by the water channel aquaporin-1 (AQP1) and aimed to determine its role in the platelet procoagulant response and thrombosis. We established that human and mouse platelets express AQP1 and localize to internal tubular membrane structures. However, deletion of AQP1 had minimal effects on collagen-induced platelet granule secretion, aggregation, or membrane ballooning. Conversely, procoagulant spreading, microvesiculation, phosphatidylserine exposure, and clot formation time were significantly diminished. Furthermore, in vivo thrombus formation after FeCl3 injury to carotid arteries was also markedly suppressed in AQP1-null mice, but hemostasis after tail bleeding remained normal. The mechanism involves an AQP1-mediated rapid membrane stretching during procoagulant spreading but not ballooning, leading to calcium entry through mechanosensitive cation channels and a full procoagulant response. We conclude that AQP1 is a major regulator of the platelet procoagulant response, able to modulate coagulation after injury or path...Continue Reading

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Citations

Jan 15, 2020·Blood Advances·Nima AbbasianMatthew T Harper
Nov 27, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Ejaife O AgbaniAlastair W Poole
Mar 21, 2020·Frontiers in Cardiovascular Medicine·Emily C Reddy, Margaret L Rand
Jun 17, 2020·International Journal of Laboratory Hematology·Ibrahim Tohidi-EsfahaniVivien M Y Chen
Jan 8, 2021·International Journal of Legal Medicine·Mizuho NosakaToshikazu Kondo
Jan 30, 2021·Blood·Karina AlthausPeter Rosenberger
Mar 13, 2021·Journal of Clinical Laboratory Analysis·Yaxin ChuRui Qiao
Apr 6, 2021·Platelets·Ejaife O Agbani, Alastair W Poole
Sep 21, 2020·The International Journal of Biochemistry & Cell Biology·Joana Campos, Alexander Brill

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Methods Mentioned

BETA
gene knockout
transmission electron microscopy
electron microscopy
tail
platelet exchange
fluorescence
flow cytometry
PCR
pull-down

Software Mentioned

PicoQuant
GraphPad Prism
LI
Fiji
Volocity
FACSDiva
COR Image Studio
FLIMfit
ImageJ
SymPhoTime64

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