title: From molecular to modular cardiology. How to interpret the millions of data that came out from large scale analysis of gene expression?
abstract: Cell biology is in transition from reductionism, to a more integrated science which is now preoccupied by molecular interactions acting in modules. Large-scale quantitative analysis of gene expression, including cDNA microarrays and proteomic analysis, is now applied to heart failure and atherosclerosis. The technology is still at the beginning and is limited by variations in the array platforms and gene products as well as sensitivity or specificity of the selected probes. These limitations are progressively going to be reduced, but still they do exist. Biological systems are scale free networks made from genes, proteins or traits that interact one another and form networks and functional modules. Networks emerge through the addition of new nodes which are preferentially attached to more connected nodes to form hubs, according to the "rich-gets-richer" mechanism, and there are large networks which include central genes (nexus). Both hubs and nexus are attractive candidate for targeting new therapy. An important study from King JY et al. (Physiol Genomics 2005; 23: 103-18) exemplifies this concept by showing the first realistic pathways to understand atherosclerosis. The 4 steps of the design are based on histological grading and microarrays analysis and include an association network constructed from PubMed and the construction of sub-networks in which genes whose expression was differentially regulated were indicated. Connectivity analysis networks revealed new important modular pathways. In heart failure, no attempts have been made to organize the data into functional modulus. Since the causes of heart failure are well documented, the problem is to identify functional modules responsible for myocardial dysfunction. Several potential functional modules can be identified so far. Indeed, cardiac remodeling results from two types of changes in gene expression, namelly the reexpression of the foetal programme which has a mechanical origin and several well documented interfering determinants that modified the basic remodelling, including senescence, obesity, diabetes, ischemia, and the neurohormonal reaction.
authors.affiliation: INSERM-U533, Ouest Génopole, faculté de médecine, 1, rue Gaston Veil, BP 53508, 44035 Nantes 1. jean.leger@nantes.inserm.fr
authors.forename: J
authors.initials: J
authors.lastname: Léger
authors.forename: B
authors.initials: B
authors.lastname: Swynghedauw
mesh_terms: D003324:Coronary Artery Disease / Q000235:genetics*; D015870:Gene Expression; D023281:Genomics; D006333:Heart Failure / Q000235:genetics*; D006801:Humans