1. Investigating the Pathways Responsible for Neuregulin-1 Protection
against Doxorubicin-induced Injury of hiPSC-derived Cardiomyocytes
Ryan Rogers
Heart Failure (HF) is a major public health problem. Over the past decade, both the
prevalence and incidence of HF have increased as life expectancy has risen, and the pressure
that has been placed on health care systems across the globe has been staggering. There is a
significant need for new therapies to combat HF. Neuregulin-1 (NRG-1) and the
erythroblastic leukemia viral oncogene homolog (ErbB) families of receptors are necessary
for cardiovascular development and are implicated in a variety of roles in adult
cardiovascular biology. Studies have shown that NRG-1/ErbB signaling has cardioprotective
effects against the cardiotoxic agent doxorubicin and may act as a mediator of reverse
remodeling. Doxorubicin is a powerful chemotherapeutic drug that can induce HF in some
patients, and in vitro models have utilized it to cause insult to cardiomyocytes. However,
NRG-1/ErbB signaling is not fully understood at the receptor level and in terms of the
downstream signaling events. NRG-1 can activate two isoforms of the ErbB receptors. Here
we extend results found in the literature on the cardioprotective effects offered by NRG-1 in
human induced pluripotent stem cell (hiPSC) derived cardiomyocytes. We also attempt to
uncover insight on the NRG-1/ErbB signaling responsible for protection utilizing siRNA
knockdown and small molecule inhibitors of intracellular signaling nodes.