Published in
Oxford University Press (OUP), Cardiovascular Research, 3(112), p. 689-701
DOI: 10.1093/cvr/cvw210
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Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase.
,
Tovar Lopez Fj,
H. (Heleen) Van Buesekamp,
Ramzi Y. (Ramzi Y.) Khamis ,
Khamis Ry,
Nicolas Foin,
Neil Bowden
and other authors.
Full text: Download
Abstract
Aims: Stent deployment causes endothelial cells (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow perturbation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration, we identified an intervention that promotes endothelial repair in stented arteries. Methods and Results: In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100lm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (P