INTERDEPENDENT RESPONSE OF CARDIAC WNT AND FOXO3A SIGNALING TO CHRONIC LOSARTAN TREATMENT

MARCHESE, FLORENCIA; GARCIA GRAS EDUARDO

mAR DEL pLATA

Congreso; REUNION CONJUNTA SAIC SAI SAFIS 2018; 2018

SAIC SAI SAFIS

The Renin-Angiotensin System (RAS) is essential to regulating blood pressure and systemic electrolyte homestasis. In the heart, Angiotensin II plays an important role in development as well as in pathophysiological processes such as hypertrophy and post-ischemic cardiac remodeling. Wnt signaling and members of the Forkhead Box O mediate some of the effects that Angiotensin II has on heart pathophysiology such as is the case with cardiac hypertrophy. This two pathways are regulated by the binding of Beta-catenin to Tcf-4 or Forkhead Box o transcription factors respectively.AIMS: we aimed to haracterize the effect that A2T1R inhibition by chronic Losartan treatment has on Wnt signaling and Foxo3a transcription in young healthy mice. MAIN METHODS: we measured a significant inhibition in the expression of Foxo3a targets, including enzymes involved in oxygen free radicals (ROS, reactive oxygen species) metabolism, albeit without changes in free oxygen radical concentration as measured by TBARS. Additionally, using RT-PCR we found six Wnt signaling components whose expression changed due to Losartan treatment. Five of those are described in the literature as involved in angiogenesis. KEY FINDINGS: summarizing we have found a coordinated response to a decrease in A2T1R signaling that appears to inhibits Foxo3a signalling and modifies the components of Wnt signaling while adapting to a smaller oxygen free radical production by Angiotensin II signal transduction