The tyrosine kinase inhibitor nilotinib targets the discoidin domain receptor DDR2 in calcific aortic valve stenosis.

ABSTRACT:

Background and purpose

Tyrosine kinase inhibitors (TKI) used to treat chronic myeloid leukaemia (CML) have been associated with cardiovascular side effects, including reports of calcific aortic valve stenosis. The aim of this study was to establish the effects of first and second generation TKIs in aortic valve stenosis and to determine the associated molecular mechanisms.

Experimental approach

Hyperlipidemic APOE*3Leiden.CETP transgenic mice were treated with nilotinib, imatinib or vehicle. Human valvular interstitial cells (VICs) were isolated and studied in vitro. Gene expression analysis was perfromed in aortic valves from 64 patients undergoing aortic valve replacement surgery.

Key results

Nilotinib increased murine aortic valve thickness. Nilotinib, but not imat

SUBMITTER: Carracedo M 

PROVIDER: S-EPMC9544120 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature