In Vitro-In Vivo Gene Expression Analysis in Atherosclerosis
Atherosclerosis, the pathologic inflammatory response to injury. of the human vessel wall, has been long recognized for its complexity of initiation, progression and ultimate appearance of clinical symptoms . Many proteins and other compounds have been implicated in atherogenesis, and this list is now growing exponentially with the recent advances in high-throughput gene expression profiling [1 2 3 4 5 6 7 8 9].Indeed, a plethora of individual genes show altered expression during atherosclerosis, but the development of intervention strategies based on such individual genes in animal models has been rather challenging. The translation into treatment of atherosclerosis in man has proven even more difficult. A clear gene-environment interaction, most notably Western-type diet and life-style, lies at the basis of disease development. This indicates that disturbed patterns of gene-expression rather than single culprit genes form the basis for the widespread penetrance of the disease in the elderly Western population. We are applying functional Genomics to the study of atherosclerosis, with the goal of characterizing healthy and diseased gene expression profiles. While our immediate objective is to characterize those genes that are differentially expressed during atherogenesis, our long-term goal is to determine how a healthy gene expression profile can be induced in the cells of the vascular wall. This implies not only to identify differentially expressed genes but also to determine their function and, most importantly, to analyze the integrated pathways and mechanisms through which their expression is regulated. In this report we will describe the use of differential display RT-PCR and cDNA microarray expression analysis to determine changes in gene expression profiles in cultured vascular endothelial cells in response to pro-and antiatherogenic stimuli. We will briefly explore the computational analysis of such gene expression profiles as detected by a custom cardiovascular microarray. Finally, we show that insights that were gained in vitro can be extended to the in vivo (atherosclerotic) vascular wall.
KeywordsGene Expression Profile Endothelial Gene International Human Genome Sequencing Consortium Transcription Factor Decoy Disturbed Pattern
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