title: Modulation of vascular cell function by bim expression.
abstract: Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-) pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, H4/444 CSC, Madison, WI 53792-4108, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Morrison
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Palenski
authors.forename: Nasim
authors.initials: N
authors.lastname: Jamali
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
authors.forename: Christine M
authors.initials: CM
authors.lastname: Sorenson