The epidermal growth factor receptor and its ligands in cardiovascular disease

Abstract

The epidermal growth factor receptor (EGFR) family and its ligands serve as a switchboard for the regulation of multiple cellular processes. While it is clear that EGFR activity is essential for normal cardiac development, its function in the vasculature and its role in cardiovascular disease are only beginning to be elucidated. In the blood vessel, endothelial cells and smooth muscle cells are both a source and a target of EGF-like ligands. Activation of EGFR has been implicated in blood pressure regulation, endothelial dysfunction, neointimal hyperplasia, atherogenesis, and cardiac remodeling. Furthermore, increased circulating EGF-like ligands may mediate accelerated vascular disease associated with chronic inflammation. Although EGFR inhibitors are currently being used clinically for the treatment of cancer, additional studies are necessary to determine whether abrogation of EGFR signaling is a potential strategy for the treatment of cardiovascular disease.

Figure 1

Epidermal growth factor receptor (EGFR) activation either by ligand binding or by transactivation mechanisms results in induction of several downstream signaling pathways.

Figure 2

EGFR and its ligands are implicated in multiple vascular disease states. EGFR acts as a switchboard for signaling many cellular processes involved in vascular disease, including cell proliferation, differentiation, survival, migration, matrix homeostasis, and inflammation. EGFR and its ligands are expressed by VSMCs and ECs as well as inflammatory cells.