Hyperglycemia-induced vasculopathy in the murine vitelline vasculature - Correlation with PECAM-1/CD31 tyrosine phosphorylation state

Maternal diabetes mellitus is associated with an increased incidence of con genital abnormalities as well as embryonic and perinatal lethality. In part icular, a wide range of cardiovascular abnormalities have been noted in chi ldren of diabetic mothers and in the offspring of diabetic animals. The vas cular system is the first Organ system to develop in the embryo and is crit ical for normal organogenesis. The organization of mesodermal cells into en dothelial and hematopoietic cells and into a complex vascular system is, in part, mediated by a series of specific cell-cell, cell-extracellular matri x, and cell-factor interactions. PECAM-1 expression has been observed durin g the earliest stages of vasculogenesis, and changes in PECAM-1 tyrosine ph osphorylation have been associated with endothelial cell migration, vasculo genesis, and angiogenesis both in vitro and in vivo, In this report we demo nstrate that exposure to hyperglycemia during gastrulation causes yolk sac and embryonic vasculopathy in cultured murine conceptuses and in the concep tuses of streptozotocin-induced diabetic pregnant mice. In addition, we cor relate the presence of yolk sac and embryonic vasculopathy with the failure of PECAM-1 tyrosine dephosphorylation during the formation of blood island s/vessels from clusters of extra-embryonic and embryonic angioblasts Fn the murine conceptus using both in vitro and in vivo models. The importance of these findings in the development of vasculopathy in the offspring of diab etic mothers and the potential effects and benefits of glucose regulation d uring the periods of vasculogenesis/angiogenesis in embryonic development a re discussed.