Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources

Proteomics and phosphoproteomics analysis of vitreous in idiopathic epiretinal membrane patients

“…The phosphoproteomic approach can detect large‐scale phosphorylation sites, and it has become a powerful tool to find key nodes in various signaling networks in pathological conditions [8]. Through the phosphoproteomic approach, the key kinases of fibrosis can be identified and antifibrotic compounds can be screened [9]. It has shown broad application prospects in the research of organ fibrosis.…”

Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy

“…Given the depth of protein identifications achieved by modern LC-MS/MS systems and the public availability of well-established tools for bioinformatics analysis, it is no surprise that proteomics has emerged as an integral tool for understanding functional changes driving HCM. For example, in a recent proteomic profiling study of fibrotic remodeling in HCM, Kuzmanov et al were able to quantify hundreds of differentially expressed phosphoproteins/kinases between affected and control samples, whose dysregulation was functionally validated to drive fibrosis [5]. Hierarchical clustering, principal component analysis (multivariate statistical analysis), and enrichment for curated kinase-substrate consensus sequences identified universal dysregulation of signaling by the protein kinase GSK3.…”

“…As recently documented in Kuzmanov et al, omics analysis of HCM models have their own strengthens and weaknesses in terms of pathobiological relevance and ease of experimental implementation [5]. These systems can provide faithful representations of CM morphology and dysfunction in response to mutations in sarcomeric proteins and other molecular perturbations associated with HCM.…”

“…There are now high-throughput omics technologies for quantifying nearly all macromolecules, including RNA and proteins, as well those for capturing physical interactions among biomolecules (e.g., protein-protein and protein-DNA interactions). The application of these tools in cardiac research increasingly combines high-performance analytical instrumentation (e.g., mass spectrometry) with computational methods (e.g., bioinformatics) to measure relative molecule abundance and infer the comparative activity of molecular pathways based on coordinated changes in functionally linked molecules [5]. Mass-spectrometry-based methods can also measure post-translational modifications, such as phosphorylation of proteins, which are important signaling processes in cardiovascular disease.…”

Beta-blocker/ACE inhibitor therapy differentially impacts the steady state signaling landscape of failing and non-failing hearts

“…Different studies have characterized transcriptomic changes in the process of heart failure 13 , 14 , but the conversion of transcriptomic data to protein function is challenging, given the poor correlation that exists between the transcriptome and the proteome of the same organ 15 , 16 . Proteomics studies such as those reported by Lau 17 and Kuzmanov 18 , 19 and colleagues have contributed to our understanding of the global changes in protein expression in animal models presenting cardiac remodeling and dysfunction. However, we still have limited knowledge of the protein- and signaling regulation characterizing a chronic state of heart failure, as well as the molecular changes that result, at the proteomics and phosphoproteomics level, following medical treatment.…”