View : 16 Download: 0

Decreased thromboembolic stroke but not atherosclerosis or vascular remodelling in mice with ROCK2-deficient platelets

Title
Decreased thromboembolic stroke but not atherosclerosis or vascular remodelling in mice with ROCK2-deficient platelets
Authors
Sladojevic, NikolaOh, Goo TaegKim, Hyung-HwanBeaulieu, Lea M.Falet, HerveKaminski, KarolFreedman, Jane E.Liao, James K.
Ewha Authors
오구택
SCOPUS Author ID
오구택scopus
Issue Date
2017
Journal Title
CARDIOVASCULAR RESEARCH
ISSN
0008-6363JCR Link1755-3245JCR Link
Citation
vol. 113, no. 11, pp. 1307 - 1317
Keywords
Rho kinasePlateletThrombosisStrokeAtherosclerosis
Publisher
OXFORD UNIV PRESS
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Aims Rho-associated coiled-coil containing kinase (ROCK)-2 is an important mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are critical for platelet function, we hypothesized that ROCK2 in platelets will play important role in thrombosis and can be potentially a target for therapeutic intervention in thromboembolic stroke. Methods and results We generated platelet-specific ROCK2-deficient mice (ROCK2(Plt-/-)) from conditional ROCK2(flox/flox) and platelet factor (PF)-4-Cre transgenic mice. Platelets from ROCK2(Plt-/-) mice were less responsive to thrombin stimulation in terms of pseudopodia formation, collagen adhesion, and in the formation of homotypic and heterotypic aggregates. This corresponded to prolonged bleeding time and delayed vascular occlusion following vessel injury. To determine whether these changes in platelet function could affect thrombotic disease, we utilized a clot-embolic model of ischaemic stroke. When pre-formed clots from ROCK2(Plt-/-) mice were injected into the middle cerebral artery of control mice, cerebral blood flow recovery occurred more rapidly, leading to decreased cerebral injury and neurological deficits, compared to pre-formed clots from control mice. Interestingly, pre-formed clots from control mice produced similar degree of cerebral injury when injected into control or ROCK2(Plt-/-) mice, suggesting that platelet ROCK2 deficiency affects clot formation but not propagation. Indeed, in a non-thrombotic intra-filament MCA occlusion model of stroke, platelet ROCK2 deletion was not protective. Furthermore, ROCK2(Plt-/-) mice exhibit similar atherosclerosis severity and vascular remodeling as control mice. Conclusion These findings indicate that platelet ROCK2 plays important role in platelet function and thrombosis, but does not contribute to the pathogenesis of atherosclerosis and vascular remodeling.
DOI
10.1093/cvr/cvx071
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE