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However, tissue homogenization and protein extraction are made difficult by tissue calcification. The reproducibility of proteome studies is key in clinical translation of the findings. Thus, we aimed to optimize a protocol for aortic valve homogenization and protein extraction and to develop a standard operating procedure (SOP), which researchers can use to maximize protein yield while reducing inter-laboratory variability. We have compared the protein yield between conventional tissue grinding in nitrogen followed by homogenization with a Potter apparatus with a more advanced bead-beating system. Once we confirmed the superiority of the latter, we further optimized it by testing the effect of beads size, the number of homogenization cycles, tube capacity, lysis buffer\/tissue mass ratio, and two different lysis buffers. Optimal protein extraction was achieved with 2.8 mm zirconium dioxide beads, in two homogenization cycles, in the presence of 20 \u00b5L RIPA buffer\/mg tissue, using 2 mL O-ring cryotubes. As a proof of concept of the usefulness of this SOP for proteomics, the AV proteome of men and women with aortic stenosis was characterized, resulting in the quantification of proteins across six orders of magnitude and uncovering some putative proteins dysregulated by sex.<\/jats:p>","DOI":"10.3390\/proteomes10030030","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T03:55:38Z","timestamp":1662004538000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Optimization of a Protocol for Protein Extraction from Calcified Aortic Valves for Proteomics Applications: Development of a Standard Operating Procedure"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-2040","authenticated-orcid":false,"given":"F\u00e1bio","family":"Trindade","sequence":"first","affiliation":[{"name":"Cardiovascular R&D Centre\u2014UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Ana F.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre\u2014UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Francisca","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre\u2014UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Diana","family":"Martins","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre\u2014UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Vera M.","family":"Mendes","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, 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Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-3596","authenticated-orcid":false,"given":"Adelino","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre\u2014UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Cardiothoracic Surgery, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-4042","authenticated-orcid":false,"given":"Bruno","family":"Manadas","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"given":"In\u00eas","family":"Falc\u00e3o-Pires","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre\u2014UnIC@RISE, Department of 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