Microarray and functional cluster analysis implicates transforming growth factor beta1 in endothelial cell dysfunction in a XXXX @entity548 model.

@entity1 @entity1707 @entity548 @entity63 @entity409 @entity1003 @entity520 @entity519 @entity17980 @entity130
BACKGROUND: @entity130 leading to @entity548 results in widespread tissue @entity519 , anaerobic metabolism, and production of inflammatory cytokines and oxidative molecules injurious to the vascular endothelium. Although @entity130 -related endothelial cell pathophysiology has been extensively studied, very little is known regarding gene transcriptional changes that occur during the event, particularly in endothelia. Thus, we employed fluorescent microarray analysis of gene transcription to elucidate critical pathways and gene products involved in @entity409 . MATERIALS AND METHODS: A @entity548 /shock (T-H/S) model mimicking the physiologic changes seen in @entity1 @entity130 was performed on 10 Yorkshire @entity1707 , consisting of 35% blood volume @entity548 followed by 6 h of full resuscitation. Aortic endothelium was analyzed by microarray and functional clusters were identified through the use of Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. RESULTS: Injured @entity1707 developed profound @entity520 , @entity1003 , massive resuscitative fluid requirements, and microscopic changes of @entity63 /reperfusion injury. While 1007 transcripts were down-regulated, 529 transcripts were up-regulated. DAVID functional clustering analysis revealed 21 significantly altered biological processes that were grouped into 12 distinct functional categories. The transforming growth factor beta (TGFb) family of genes was the most interrelated. In addition, @entity17980 ( @entity17980 ) signaling members and leukocyte chemoattractants were also altered. CONCLUSIONS: Our model identified two major signaling pathways, TGFb and @entity17980 , which undergo early transcriptional changes in injured endothelial cells. Our results suggest that TGFb and @entity17980 may play a crucial role in the development of @entity130 leading to increased vascular permeability during shock- @entity130 .
