BET Bromodomain Blockade Mitigates Intimal Hyperplasia in Rat Carotid Arteries.

ABSTRACT:

Background

Intimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic "readers" including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known.

Methods

We investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model.

Results

While BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(-), abrogated platelet-

SUBMITTER: Wang B 

PROVIDER: S-EPMC4740308 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature