Role of FAK signaling in chagasic cardiac hypertrophy

On the other hand, PI3K-AKT/nitric oxide (NO) signaling has been demonstrated to be implicated in cardiac myocyte remodeling of chagasic cardiomyopathy. C57Bl/6 mice infected with Colombian strain induced PI3K-AKT/NO signaling pathway activation with cardiac hypertrophy evidenced in the acute (30 dpi) and in the early chronic phase (90 dpi) of T. cruzi infection, showing increased mRNA level of hypertrophic markers. A remarkable feature is that ERK1/2 and AKT has been highlighted as downstream effector of FAK activation and FAK signaling may also regulate NF-kB activation, suggesting that chagasic cardiac hypertrophy may be regulated by complex regulatory interactions involving interlaced networks of multiple signaling pathways.

Overall, our data contribute with new insights in the regulation of cardiac hypertrophy induced by T. cruzi infection. We demonstrated that the FAK signaling pathway regulates the hypertrophic process in chronic chagasic cardiomyopathy. Cardiac overload induced by ET-1-mediated extracellular matrix remodeling and tissue damage triggers the hypertrophic response via ET-1-ERK1/2-FAKS910 and integrin-FAKY397-ERK1/2, leading to activation of the fetal gene program, heart failure and hypertrophy. Further studies will be carried out to evaluate the effect of FAK signaling inhibitors in the therapy of Chagas disease.