Title:Cardiovascular Effects of Neuregulin-1/ErbB Signaling: Role in Vascular Signaling and Angiogenesis
Volume: 20
Issue: 30
Author(s): Nadia Hedhli, April Kalinowski and Kerry S. Russell
Affiliation:
Keywords:
erbB, neuregulin, endothelial cells, trastuzumab, cancer, heart failure, smooth muscle cells, angiogenesis.
Abstract: The NRG/erbB pathway has emerged as an important therapeutic target for cancer growth as well as cardiac related diseases.
This discovery stems back to findings showing that overexpression of erbB2 receptors increases the metastatic potential of breast cancer
in patients. Blocking this receptor using a monoclonal antibody (trastuzumab) inhibits tumor growth and offers significantly improved
outcomes. However, excitement over this discovery was tempered by data showing that trastuzumab-treated patients have an increased
risk of developing cardiac dysfunction, limiting the clinical potential of this novel agent. This finding suggested an important protective
effect of the erbB signaling pathway on cardiac survival and homeostasis. Further investigation has shown that endothelial-derived
neuregulin (a key ligand for erbB receptors) has a protective paracrine effect on cardiac cells as well as vascular smooth muscle cells in
the setting of an injury. Since endothelial cells contain erbB receptors, they are also targets for autocrine signaling via this pathway, an
important mediator of vascular preservation and angiogenic responses of endothelium. In this review we summarize important clinical
findings as well as animal and cellular models that illustrate the signaling pathways involved in vascular cell regulation of cardiomyocyte
survival and angiogenesis via the NRG/erbB pathway.
