Genetic regulation of systemic angiogenesis in the mouse lung.
The work in this study takes advantage of a new experimental model in the mouse that completely isolates the angiogenic process from the direct effects of ischemia. The model also leads to lung angiogenesis that mimics the vascular source of many lung pathologies, and allows investigation of the temporal and spatial factors that can promote or inhibit angiogenesis. This work describes the expression patterns of genes relevant to pro-angiogenic signals and conditions in response to ischemia in the lung. The most notable changes were increases in the expression of genes involved in inflammation and tissue remodeling. In particular, the results confirm a important role of ELR+ CXC chemokines as proangiogenic signals. In addition, the experimental findings in this mouse lung model show that lung ischemia, rather than hypoxia, is the essential trigger for angiogenesis. Results from this model also suggest potential approaches for determining critical pathways and potential therapeutic strategies related to the control of angiogenesis.
Mitzner
W
W
The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA. wmitzner@jhsph.edu
Srisuma
S
S
Wagner
E
E
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism*; D008168:Lung / Q000098:blood supply*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011651:Pulmonary Artery / Q000601:surgery; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors