Control of vascular cell differentiation by homeobox transcription factors

Homeobox genes are a family of transcription factors with a highly conserved DNA-binding domain that regulate cell proliferation, differentiation, and migration in many cell types in diverse organisms. These properties are responsible for their critical roles in regulating pattern formation and organogenesis during embryogenesis. The cardiovascular system undergoes extensive remodeling during embryogenesis, and cardiovascular remodeling in the adult is associated with normal physiologic processes such as wound healing and the menstrual cycle, and disease states such as atherosclerosis, tumor-induced angiogenesis, and lymphedema. Aside from their roles in the formation of the embryonic vascular system, homeobox genes recently have been implicated in both physiologic and pathologic processes involving vascular remodeling in the adult, such as arterial restenosis after balloon angioplasty, physiologic and tumor-induced angiogenesis, and lymphangiogenesis. Understanding how homeobox genes regulate the phenotype of smooth muscle and endothelium in the vasculature will improve insight into the molecular mechanisms behind vascular cell differentiation and may suggest therapeutic interventions in human disease.