Dec. 1 /PRNewswire/ -- A study published today in The Journal of Biological Chemistry, and a separate paper published earlier in the American Heart Association's journal, Arteriosclerosis, Thrombosis, and Vascular Biology (October 2000), report the discovery by scientists at CV Therapeutics, Inc. (Nasdaq: CVTX - news) of genes previously unknown to be involved in the development of atherosclerosis and vascular damage following angioplasty, respectively. The studies utilized genomic methodologies that allow CVT scientists to examine expression patterns of multiple genes affected by vascular injury.
``Determining the molecular pathways that lead to these damaging processes may someday help identify future drug development targets to modify and potentially reverse the progression of vascular disease,'' said Dov Shiffman, Ph.D., Associate Director, Genomics, CV Therapeutics, the lead investigator of both studies. ``We are interested in understanding the pathology of vascular disease. These papers demonstrate the informative potential of RNA profiling in vascular disease models. We are in the process of expanding this approach to generate a broader database of gene expression patterns of whole vessel models and in vascular cells.''
Vascular damage caused by atherosclerosis or by angioplasty-induced restenosis may result in obstruction of blood flow. ``While earlier research has shown that vessel injury and the development of atherosclerotic plaques stimulate certain genes to switch on or off, these studies only examined a small number of genes,'' continued Dr. Shiffman. ``In contrast, the methodologies we used dramatically reduced the amount of time typically necessary to monitor the expression level of thousands of genes.''
In the study published in The Journal of Biological Chemistry, entitled, ``Large-scale gene expression analysis of cholesterol loaded macrophages,'' CVT scientists used microarray technology to examine what makes a macrophage cell become a foam cell and what gene expression changes occur during this process. These foam cells, or cholesterol-engorged macrophages, are characteristic of atherosclerotic lesions. Their continuous presence in these lesions is thought to contribute to the development and potential rupture of atherosclerotic lesions. Determining how and why a macrophage becomes a foam cell can lead to interventions that modify or reverse the development of foam cells and, ultimately, reverse the development of atherosclerotic plaques. CVT scientists found that foam cells have a modified inflammatory potential, and found strong indicators of the involvement of nuclear receptor signaling in the process of foam cell formation. Several genes that have never been associated with cholesterol uptake or plaque formation were also identified.
In the study entitled, ``Determination of temporal expression patterns for multiple genes in the rat carotid artery injury model,'' published in Arteriosclerosis, Thrombosis and Vascular Biology, scientists at CVT employed real-time PCR technology to examine which genes are switched on or off as restenosis, a reocclusion of vessels, develops in an animal model. This study identified several genes previously unknown to be involved in the process of lesion development following balloon angioplasty. It also found that groups of genes with similar functions had similar expression patterns. Approximately 20 to 50 percent of angioplasty patients have some degree of restenosis, following initial balloon angioplasty.... |
