Abstract
Systems biology approaches including proteomics are becoming more widely used in cardiovascular research. In this review article, we focus on the application of proteomics to the cardiac extracellular matrix (ECM). ECM remodelling is a hallmark of many cardiovascular diseases. Proteomic techniques using mass spectrometry (MS) provide a platform for the comprehensive analysis of ECM proteins without a priori assumptions. Proteomics overcomes various constraints inherent to conventional antibody detection. On the other hand, studies that use whole tissue lysates for proteomic analysis mask the identification of the less abundant ECM constituents. In this review, we first discuss decellularization-based methods that enrich for ECM proteins in cardiac tissue, and how targeted MS allows for accurate protein quantification. The second part of the review will focus on post-translational modifications including hydroxylation and glycosylation and on the release of matrix fragments with biological activity (matrikines), all of which can be interrogated by proteomic techniques.
Highlights
Proteomic techniques using mass spectrometry (MS) provide a platform for the comprehensive analysis of proteins, thereby facilitating the implementation of systems biology approaches and circumventing the limitations of a traditional, reductionist approach adopted by techniques like western blotting that are based on a priori assumptions of the proteins to be investigated
Proteomics is without the constraints of antibody-dependent protein detection and has the capability of detecting post-translational modifications (PTMs), which is beyond the means of gene expression platforms.[1]
As recently highlighted in a scientific statement of the American Heart Association[55]; it is anticipated that proteomics research will further our understanding of mechanisms of cardiovascular disease (CVD) with one important aspect being the elucidation of extracellular matrix (ECM) composition in healthy and diseased cardiovascular tissues
Summary
Proteomic techniques using mass spectrometry (MS) provide a platform for the comprehensive analysis of proteins, thereby facilitating the implementation of systems biology approaches and circumventing the limitations of a traditional, reductionist approach adopted by techniques like western blotting that are based on a priori assumptions of the proteins to be investigated. Proteomics is without the constraints of antibody-dependent protein detection and has the capability of detecting post-translational modifications (PTMs), which is beyond the means of gene expression platforms.[1]. Proteomics has been successfully applied to study the ECM, providing unprecedented insights into its biology and pathological remodelling.[2,3,4,5] In the present review, we describe the utility of ECM proteomics as applied to cardiovascular research and the potential pitfalls. We highlight the means to overcome common proteomic challenges and present translational applications of proteomic datasets
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