Genetic Control of Vascular Remodeling

Sunnybrook &Women'S Coll Hlth Scis Ctr, Toronto ON

Investigators

Linked publications & trials

Abstract

Angiogenesis, the growth of blood vessels from pre- existing vessels, which is known to play a pivotal role in the progression of several different diseases, including diabetic retinopathy, arteriosclerosis and cancer. To-date, virtually all genes that have been shown to play a role in early vascular development of the embryo, are also expressed in the endothelium of these diseased tissues. Thus, implies that the disregulation of gene expression in the endothelium in these diseased tissues recapitulates the genes expressed in the activated endothelium of the developing embryo. The genetic control of this vessel growth is currently poorly understood, however several studies using gene-targeting in mice have revealed that numerous diverse signaling pathways produce overlapping defects in vascular remodeling. The working hypothesis for this proposal is that the defects observed in these different mouse mutants are the consequence of misregulation of a common subset of genes whose expression control vascular remodeling. This research will use gene expression profiling by gene chip and SAGE analysis to examine the genes expressed in four different mouse mutants that affect very different signaling pathways and result in overlapping vascular remodeling defects. The differential expression of genes in the heart and yolk sacs of the Tek/Tie2, Endoglin, VEGFR3, and Notch1 mouse mutants will be compared. This work will provide considerable insight into the role of these disparate signaling modalities in the angiogenic response.