Submitted May 31, 2006
Accepted September 1, 2006
Phenotypic heterogeneity is an evolutionarily conserved feature of the endothelium
Kiichiro Yano, Daniel Gale, Steffen Massberg, Pavan K Cheruvu, Rita Monahan-Earley, Ellen S Morgan, David Haig, Ulrich H von Andrian, Ann M Dvorak, and William C Aird*
Beth Israel Deaconess Medical Center, Boston, MA
CBR Institute for Biomedical Research, Boston, MA
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA
* Corresponding author; email: waird{at}bidmc.harvard.edu.
Mammalian endothelial cells (ECs) display marked phenotypic heterogeneity. Little is known about the evolutionary mechanisms underlying EC heterogeneity. The last common ancestor of hagfish and gnathostomes was also the last common ancestor of all extant vertebrates, which lived some time more than 500 million years ago. Features of ECs that are shared between hagfish and gnathostomes can be inferred to have already been present in this ancestral vertebrate. The goal of this study was to determine whether hagfish endothelium displays phenotypic heterogeneity. Electron microscopy of the aorta, dermis, heart, and liver revealed ultrastructural heterogeneity of the endothelium. Immunofluorescent studies demonstrated marked differences in lectin binding between vascular beds. Intravital microscopy of the dermis revealed histamine-induced adhesion of leukocytes in capillaries and post-capillary venules, but not arterioles. Together, these data suggest that structural, molecular and functional heterogeneity of the endothelium evolved as an early feature of this cell lineage.