Current Proteomics - Volume 3, Issue 3, 2006

Cardiovascular diseases are among the leading cause of morbidity and mortality in Western societies and developing countries. The ability to investigate the complete proteome provides a critical tool toward elucidating the complex and multifactorial basis of cardiovascular biology, especially disease processes. In recent years the proteome (and secretome) of the most relevant cellular elements (myocytes, endothelial cells, smooth muscle cells, foam cells, circulating monocytes, platelets) of the cardiovascular system has begun to be depicted with the construction of two dimensional gel electrophoresis maps and databases. The development of differential proteomics allows examination of global alterations in protein expression in the cardiovascular diseases and identifies new potential proteins implicated in the genesis of myocardial infarction, heart failure, stroke, and peripheral arterial disease. Moreover, different strategies have been used to discover novel potential biomarkers that could be related with cardiovascular risk. The multi-factorial nature of cardiovascular diseases necessitates the use of biomarkers for early detection, for monitoring the response to therapy and to predict clinical outcome. In this review we summarize the current status of different proteomic technologies and recent findings that can help to understand the mechanisms implicated in the cardiovascular diseases. The application of proteomics to cardiovascular disease holds great promise and offer exciting advances toward predictive, preventive, and personalized medicine.

The tendency of the proteins to aggregate (i.e., their so-called Lego property) is viewed as a necessary feature of proteins to build up molecular networks, which are the informational substrate that allows integrative actions of cells and hence of tissues. Thus, the concept of physiological protein mosaics is discussed not only as the basis for the formation of structural elements of the cell and of the extra-cellular matrix, but also as the main component of molecular networks. Against this background, the hypothesis is introduced that prion-like properties of some proteins have a possible physiological meaning for the formation of physiological protein mosaics and hence of complex molecular networks. Protein misfolding and the Lego property can favour the formation of unwanted protein aggregates. On this basis, the concept of pathological mosaics is introduced as the most frequent consequence of alterations in the three dimensional structures of proteins, thus representing a feature characterising the conformational protein diseases. It is postulated that pathological protein mosaics affect the structure and function of the global molecular network enmeshing the whole central nervous system leading to neurodegenerative disease, the most clear cut example being Prion disease.

There are a large number of software packages available, both commercial and academic, to assist researchers in modeling protein networks. In this paper, we briefly review some of the more commonly used tools and focus on the current state of the Systems Biology Workbench (SBW), a modular framework that connects modeling and analysis applications, enabling tools to reuse each other's capabilities. We describe how users and developers perceive SBW and then describe the currently available SBW modules.

Studies of protein-protein interaction networks provide a valuable framework for understanding the functional processes of living systems, because many biological processes are triggered by the interaction or binding of molecules. Display technologies are powerful tools, both for selecting and engineering polypeptides or proteins with novel functions and for analyzing protein interactions. Display technologies can be divided into two types: cell (or viral)-based display, and cell-free display. These display systems permit multiple rounds of affinity selection, and finally the amino acid sequence of the displayed protein can be determined by sequencing the corresponding DNA (or RNA). Display technologies are currently applied to select antibodies, peptides, enzymes, and biologically interacting partners. Because each display technology has various advantages and limitations, both in theory and in practice, one should adapt an appropriate method for a particular purpose. In this review, we summarize recent advances in and prospects for display technologies.