%0 Journal Article
%T Modulation of Vascular Cell Function by Bim Expression
%A Margaret E. Morrison
%A Tammy L. Palenski
%A Nasim Jamali
%A Nader Sheibani
%A Christine M. Sorenson
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/297537
%X 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. 1. Background Apoptosis facilitates the removal of unwanted cells during development and maintains tissue homeostasis. Bcl-2 family members influence apoptosis in either a positive or a negative fashion. Family members are classically grouped into three subclasses including one that inhibits apoptosis, a second that induces apoptosis and a third contains that family members, such as Bim, that only have a BH3 domain that binds antiapoptotic family members to promote apoptosis [1]. Bcl-2 exerts opposing effects with regards to apoptosis compared with Bim, consistent with their opposing effects on cell adhesion and migration [2]. The removal of a single allele of Bim is sufficient to prevent the degenerative disorders caused by Bcl-2 deficiency [3, 4]. Bim expression is also essential for apoptosis of a wide range of growth factor deprived cells [5], including endothelial cells and pericytes [6]. Therefore, improper modulation of apoptosis could impact the development and/or the pathogenesis of many diseases including diabetic retinopathy. Murine retinal vascular development proceeds after birth and is complete by postnatal day 21 (P21). Remodeling and pruning of the retinal vasculature continue until P42 [7, 8]. Pro- and anti-apoptotic factors regulate apoptosis during retinal vascular development,
%U http://www.hindawi.com/journals/ijcb/2013/297537/