Devo Lect 16 - Circulation Flashcards
Vasculogenesis
Initial formation of blood vessels; basically need formation of tubes, heart pumping, and connections to the heart
Differentiation in Vasculogenesis
Mesoderm cell; FGF2 makes it into hemagioblast; lineages split: angioblast becomes endothelial cell for vessels (VEGF), pluripotent hematopoietic stem cell
VEGF
Vascular endothelial growth factor; main GF in formation of blood vessels
Steps in vasculogenesis
Yolk sac endoderm forms tube, blood islands form (hemangioblasts), endothelial cells and blood stem cells differentiate ?????
Angiogenesis
Formation of blood vessels from pre-existing one; sprouting caused by VEGF; connections finished with other GF
Understanding of blood vessel formation
cancer studies from Dr. Judah Folkmann; put piece of tumor in rabbit cornea which caused angiogenesis there; purified VEGF after 10 years
Tumor-induced angiogenesis
Factors like FGF2, VEGF; tumors grow way faster with blood vessels (more nutrients, and wastes removed); also allow cells to metastasize because connections in vessels are loose
Anti-angiogenesis factors
Angiostatin, endostatin, avastin (Ab to VEGF); most of body not undergoing angiogenesis (except uterus)
Avastin
Antibody to VEGF; minimizes metastasis and increases survivorship
Thalidomide
causes focalmelia in infant because it blocks angiogenesis; needs to be metabolized
Gene therapy for VEGF
Dominant negative receptors, or therapeutic protein via adenovirus
Problems with gene therapy for VEGF
Problems with wound healing, leaky blood vessels prone to hemorrhage