Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization.
Microenvironmental cues mediate postnatal neovascularization via modulation of endothelial cell and bone marrow-derived endothelial progenitor cell (EPC) activity. Numerous signals regulate the activity of both of these cell types in response to vascular injury, which suggests that parallel mechanisms regulate angiogenesis in the vascular beds of both the heart and bone marrow. To identify mediators of such shared pathways, in vivo bone marrow/cardiac phage display biopanning was performed and led to the identification of tenascin-C as a candidate protein. Functionally, tenascin-C inhibits cardiac endothelial cell spreading and enhances migration in response to angiogenic growth factors. Analysis of human coronary thrombi revealed tenascin-C protein expression colocalized with the endothelial cell/EPC marker Tie-2 in intrathrombi vascular channels. Immunostains in the rodent heart demonstrated that tenascin-C also colocalizes with EPCs homing to sites of cardiac angiogenic induction. To determine the importance of tenascin-C in cardiac neovascularization, we used an established cardiac transplantation model and showed that unlike wild-type mice, tenascin-C-/- mice fail to vascularize cardiac allografts. This demonstrates for the first time that tenascin-C is essential for postnatal cardiac angiogenic function. Together, our data highlight the role of tenascin-C as a microenvironmental regulator of cardiac endothelial/EPC activity.
Ballard
Victoria L T
VL
Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
Sharma
Arti
A
Duignan
Inga
I
Holm
Jacquelyne M
JM
Chin
Andrew
A
Choi
Ruby
R
Hajjar
Katherine A
KA
Wong
Shing-Chiu
SC
Edelberg
Jay M
JM
D000375:Aging; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D003331:Coronary Vessels / Q000254:growth & development*; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism
D019063:Tenascin