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Application of an Integrative Computational Framework in Trancriptomic Data of Atherosclerotic Mice Suggests Numerous Molecular Players

DOI: 10.1155/2012/453513

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Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study aims to exploit bioinformatic tools in order to analyze microarray data of atherosclerotic aortic lesions of ApoE knockout mice, a model widely used in atherosclerosis research. In particular, a dynamic analysis was performed among young and aged animals, resulting in a list of 852 significantly altered genes. Pathway analysis indicated alterations in critical cellular processes related to cell communication and signal transduction, immune response, lipid transport, and metabolism. Cluster analysis partitioned the significantly differentiated genes in three major clusters of similar expression profile. Promoter analysis applied to functional related groups of the same cluster revealed shared putative cis-elements potentially contributing to a common regulatory mechanism. Finally, by reverse engineering the functional relevance of differentially expressed genes with specific cellular pathways, putative genes acting as hubs, were identified, linking functionally disparate cellular processes in the context of traditional molecular description. 1. Introduction Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide, characterized by the progressive accumulation of lipid and fibrous depositions in the vessel wall of medium-sized and large arteries. Although it has traditionally been viewed as simple deposition of lipids within the vessel wall, it is now assumed that atherosclerosis is a multifactorial disease that involves several genes and proteins, activated during its genesis, progress, and phenotypic manifestation. During atherogenesis, a complex endothelial activation and dysfunction induced by elevated and modified low-density lipoproteins and many other factors leads to a compensatory inflammatory response [1]. Current evidence supports a central role for inflammation, in all phases of the atherosclerotic process. Substantial biological data implicate inflammatory pathways in early atherogenesis, in the progression of lesions, and finally in the thrombotic complications of this disease [2]. Clinical investigations, population studies, and cell culture experiments have provided important clues to the pathogenesis of atherosclerosis. However, the use of animal models has had a crucial contribution in the research of the atherosclerotic course. Atherosclerosis will not be developed in laboratory mice under normal conditions. However, targeted deletion of the gene


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