Abstract 16553: FAST Kinase Domain Containing Protein 1 Prevents Myocardial Infarction Induced Rupture
We have previously identified the mitochondrial protein FAST Kinase Domain containing protein 1 (FASTKD1) as a novel cyclophilin-D binding protein, that protects cells from oxidative stress induced cell death in vitro. However, the role of FASTKD1 in the myocardium in vivo is unknown. Therefore we developed cardiac myocyte specific FASTKD1 transgenic mice to test the effects of this protein on myocardial infarction (MI). Three independent lines of mice with cardiac myocyte specific overexpression of FASTKD1 to varying degrees were generated. These mice displayed normal cardiac morphology and function at the gross and microscopic levels. Isolated cardiac mitochondria from all transgenic mouse lines showed normal mitochondrial function, ATP levels, and mitochondrial permeability transition pore activity. Mice from the highest expressing line were subjected to 8-weeks of permanent coronary ligation. However, approximately 40% of non-transgenic mice underwent left ventricular free wall rupture within the first 7-days post-MI compared to 0% of FASTKD1 overexpressing mice. To better assess this difference in rupture incidence, mice were examined at 3-days post-MI. FASTKD1 overexpression did not alter infarct size itself. However, increased FASTKD1 levels resulted in decreased neutrophil infiltration alongside increased macrophage numbers in the border and scar regions compared to non-transgenic mice. Moreover, FASTKD1 transgenics exhibited elevated levels of the extracellular matrix protein periostin, which previous studies have shown to modulate rupture incidence. Thus, cardiac specific overexpression of FASTKD1 renders mice resistant to MI-induced cardiac rupture and induces altered inflammatory and ECM responses following MI.
Author Disclosures: K.D. Marshall: None. R. Roy: None. M. Krenz: None. C.P. Baines: None.
- © 2016 by American Heart Association, Inc.