Host Responses in CV Injury Leading to Heart Failure

Mech Stretch Stress Activ'r Infla mm'n

Growth Factors Oxidative Stress MAP/SAP kinases

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Ion Channel Ca" Reg Pnotein Transitions

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Activation of Eiastases/MMPs & Integrlns in Matrix

Cytoskeletal, Cell Shape 8 Contrae Protein Changes

Pftenotype Remodeling: Initially Adaptive

Uncontrolled Activation - Maladaptive (Apoptosis, Ca" Overload)

Host — Genetic Background

Fig. 4.1 The complex known pathways contributing to the process of heart failure. The traditional approach of investigating a single molecular target is intrinsically limited due to the network nature of the disease process.

The microarray will permit the scientist to examine multiple targets simultaneously, to determine potential molecular interactions, and identify novel members of participating pathways.

Strengths of Microarray Technology

DNA microarray enables researchers for the first time to visualize global patterns of gene expression under different conditions. A long way to express a simple thought. The variation in the expression of a single gene is richer than the allelic variation in its sequence. Finding the link between the expression variation and phenotypic variation may provide clues to the biological roles of gene(s) to identify the molecular basis of phenotypic variation among cells and individuals. To generate a gene expression profile of a condition (s) is to identify the up- or down-regulation of gene (s) expression which can be both the cause and effect in a disease state. To study the global changes involving thousands of genes is not possible without microarray. A large portion of the genome can be interrogated simultaneously to identify the common cluster of genes with similar expression pattern which may reflect a similar function. The exceptions or unknown members may help to identify functionally important novel genes. Moreover, the temporal sequence of gene expression can be followed with microarray technology. Finally, microarray technologies can be used to develop diagnostic tools, either to identify the markers or to use the global geneexpression information for classifying different stages of the disease state, by using a subset of global candidate genes relevant to the disease (Fig. 4.2). The aggregate database is also useful to develop new

Fig. 4.2 One of the potential applications of microarrays in the setting of heart failure is by developing disease relevant "chips" in the future, once the relevance of these genes are known. For example, from a global set of can-

Potential Global Candidates in Heart Failure

Fig. 4.2 One of the potential applications of microarrays in the setting of heart failure is by developing disease relevant "chips" in the future, once the relevance of these genes are known. For example, from a global set of can-

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