Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia.

ABSTRACT:

Background and aims

Histone methyltransferases are emerging targets for epigenetic therapy. DOT1L (disruptor of telomeric silencing 1-like) is the only known methylation writer at histone 3 lysine 79 (H3K79). It is little explored for intervention of cardiovascular disease. We investigated the role of DOT1L in neointimal hyperplasia (IH), a basic etiology of occlusive vascular diseases.

Methods and results

IH was induced via balloon angioplasty in rat carotid arteries. DOT1L and its catalytic products H3K79me2 and H3K79me3 (immunostaining) increased by 4.69 ± 0.34, 2.38 ± 0.052, and 3.07 ± 0.27 fold, respectively, in injured (versus uninjured) carotid arteries at post-injury day 7. Dot1l silencing via shRNA-lentivirus infusion in injured arteries reduced DOT1L, H3K79me2, and

SUBMITTER: Huang Y 

PROVIDER: S-EPMC7503165 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature