Little definitive information is known concerning how new blood vessels form or regress and it is likely that novel endothelial cell proteins exist which will specifically regulate these uniquely endothelial cell processes. An in vitro model of capillary morphogenesis using human endothelial cells resuspended in three dimensional collagen matrices which recapitulates steps during angiogenesis in endothelial cells has been established. Additionally a model of endothelial cell apoptosis with p53 over expression has also been developed. These models have been used to identify genes differentially expressed during capillary morphogenesis and endothelial apoptosis. A number of genes have been identified that are differentially identify during capillary morphogenesis (CMG) and apoptosis associated processes (AAG). Some of these genes are novel and some are related or identical to known genes. This proposal has three objectives (1) to identify novel capillary morphogenesis genes during VEGF induced angiogenesis in vivo (2) to analyze the expression of nine novel CMGs and several known CMGs isolated from an in vitro capillary formation model during VEGF induced angiogenesis in vivo and (3) to identify known and novel genes that regulate endothelial cell apoptosis during capillary morphogenesis/regression and following p53 induction.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL059373-01
Application #
2452609
Study Section
Pathology A Study Section (PTHA)
Program Officer
Marks, Cheryl L
Project Start
1998-03-15
Project End
2002-02-28
Budget Start
1998-03-15
Budget End
1999-02-28
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Wu, Qing; Zhang, Jiaojiao; Koh, Wonshill et al. (2015) Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in zebrafish. FASEB J 29:4989-5005
Kim, Dae Joong; Martinez-Lemus, Luis A; Davis, George E (2013) EB1, p150Glued, and Clasp1 control endothelial tubulogenesis through microtubule assembly, acetylation, and apical polarization. Blood 121:3521-30
Zheng, Xiangjian; Xu, Chong; Smith, Annie O et al. (2012) Dynamic regulation of the cerebral cavernous malformation pathway controls vascular stability and growth. Dev Cell 23:342-55
Stratman, Amber N; Davis, George E (2012) Endothelial cell-pericyte interactions stimulate basement membrane matrix assembly: influence on vascular tube remodeling, maturation, and stabilization. Microsc Microanal 18:68-80
Sacharidou, Anastasia; Stratman, Amber N; Davis, George E (2012) Molecular mechanisms controlling vascular lumen formation in three-dimensional extracellular matrices. Cells Tissues Organs 195:122-43
Xu, Ke; Sacharidou, Anastasia; Fu, Stephen et al. (2011) Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling. Dev Cell 20:526-39
Senger, Donald R; Davis, George E (2011) Angiogenesis. Cold Spring Harb Perspect Biol 3:a005090
Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N et al. (2011) RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG. Blood 118:1145-53
Chan, Aubrey C; Drakos, Stavros G; Ruiz, Oscar E et al. (2011) Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice. J Clin Invest 121:1871-81
Davis, George E; Stratman, Amber N; Sacharidou, Anastasia et al. (2011) Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting. Int Rev Cell Mol Biol 288:101-65

Showing the most recent 10 out of 42 publications