LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

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

Photo by mertguller from unsplash

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… Click to show full 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 (ROCK2Plt-/-) from conditional ROCK2fl°x/fl°x and platelet factor (PF)-4-Cre transgenic mice. Platelets from ROCK2Plt-/- 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 ROCK2Plt-/- 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 ROCK2Plt-/- 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, ROCK2Plt-/- 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.

Keywords: thromboembolic stroke; rock2; mice; rock2 deficient; platelet; atherosclerosis

Journal Title: Cardiovascular Research
Year Published: 2017

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.