Sunitinib mediates mitochondrial ROS production in adult rat cardiac fibroblasts via CaMKII oxidation

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Abstract

Ca2+/calmodulin dependent protein kinase II (CaMKII) is a central mediator of Ca2+-induced signalling in the heart and regulates both normal cardiac physiology and pathology. Sunitinib malate is an oral Type I tyrosine kinase inhibitor (TKI) known to inhibit more than 50 kinases, with anti-angiogenic and anti-proliferative effects affiliated with off-target cardiotoxicity. Previous work has shown that chronic sunitinib treatment significantly increases CaMKII expression and activity and this correlates with significant cardiac dysfunction in vivo.1 Mitochondrial dysfunction, mediated by increased mitochondrial Ca2+ and resultant mitochondrial ROS production, has been proposed as an underlying mechanism for TKI-induced cardiotoxicity in cardiomyocytes.2 However, little is known of how TKIs may affect the non-contractile cells of the heart. Here, we have investigated whether sunitinib treatment increases mitochondrial ROS production in cardiac fibroblasts (CF) and whether CaMKII may play a role in this potential cardiotoxic mechanism
Original languageEnglish
Article numberOP8
Number of pages1
JournalHeart
Volume106
Issue numberSuppl 1
DOIs
Publication statusPublished - 5 Apr 2020
EventScottish Cardiovascular Forum – 23rd annual meeting - University of Strathclyde, Glasgow, United Kingdom
Duration: 1 Feb 20201 Feb 2020
Conference number: 23rd

Keywords

  • cardiac physiology
  • sunitinib
  • cardiac fibroblast

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