{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:44:42Z","timestamp":1770777882508,"version":"3.50.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T00:00:00Z","timestamp":1678492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010447","name":"German Center of Cardiovascular Research (DZHK)","doi-asserted-by":"publisher","award":["81X2710178 81564\/100"],"award-info":[{"award-number":["81X2710178 81564\/100"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Left ventricular (LV) reverse remodeling after aortic valve (AV) surgery is less predictable in chronic aortic regurgitation (AR) than in aortic stenosis (AS). We aimed to disclose specific LV myocardial protein signatures possibly contributing to differential disease progression. Global protein profiling of LV myocardial samples excised from the subaortic interventricular septum in patients with isolated AR or AS undergoing AV surgery was performed using liquid chromatography\u2013electrospray ionization\u2013tandem mass spectrometry. Based on label-free quantitation protein intensities, a logistic regression model was calculated and adjusted for age, sex and protein concentration. Web-based functional enrichment analyses of phenotype-associated proteins were performed utilizing g:Profiler and STRING. Data are available via ProteomeXchange with identifier PXD039662. Lysates from 38 patients, including 25 AR and 13 AS samples, were analyzed. AR patients presented with significantly larger LV diameters and volumes (end-diastolic diameter: 61 (12) vs. 48 (13) mm, p &lt; 0.001; end-diastolic volume: 180.0 (74.6) vs. 92.3 (78.4), p = 0.001). A total of 171 proteins were associated with patient phenotype: 117 were positively associated with AR and the enrichment of intracellular compartment proteins (i.e., assigned to carbohydrate and nucleotide metabolism, protein biosynthesis and the proteasome) was detected. Additionally, 54 were positively associated with AS and the enrichment of extracellular compartment proteins (i.e., assigned to the immune and hematopoietic system) was observed. In summary, functional enrichment analysis revealed specific AR- and AS-associated signatures of LV myocardial proteins.<\/jats:p>","DOI":"10.3390\/cells12060878","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T06:52:13Z","timestamp":1678690333000},"page":"878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic Analysis in Valvular Cardiomyopathy: Aortic Regurgitation vs. Aortic Stenosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-9555","authenticated-orcid":false,"given":"Theresa","family":"Holst","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Augsburg University Hospital, Stenglinstra\u00dfe 2, 86156 Augsburg, Germany"},{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Ameling","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Stra\u00dfe 8, 17487 Greifswald, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Augsburg University Hospital, Stenglinstra\u00dfe 2, 86156 Augsburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"Christ","sequence":"additional","affiliation":[{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"},{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Gedeon","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"},{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Eschenhagen","sequence":"additional","affiliation":[{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"},{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Reichenspurner","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1507-0402","authenticated-orcid":false,"given":"Elke","family":"Hammer","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Stra\u00dfe 8, 17487 Greifswald, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evaldas","family":"Girdauskas","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Augsburg University Hospital, Stenglinstra\u00dfe 2, 86156 Augsburg, Germany"},{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1016\/j.jacc.2012.02.093","article-title":"Calcific aortic stenosis: A disease of the valve and the myocardium","volume":"60","author":"Dweck","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1161\/CIRCULATIONAHA.104.488825","article-title":"Valvular heart disease: Aortic regurgitation","volume":"112","author":"Bekeredjian","year":"2005","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/eurheartj\/ehv548","article-title":"Heart failure: When form fails to follow function","volume":"37","author":"Katz","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/eurheartj\/ehab395","article-title":"2021 ESC\/EACTS Guidelines for the management of valvular heart disease","volume":"43","author":"Vahanian","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1053\/j.jvca.2018.11.013","article-title":"Assessment of Left Ventricular Reverse Remodeling by Cardiac MRI in Patients Undergoing Repair Surgery for Severe Aortic or Mitral Regurgitation","volume":"33","author":"Seldrum","year":"2019","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1161\/CIRCULATIONAHA.108.812685","article-title":"Persistent diastolic dysfunction late after valve replacement in severe aortic regurgitation","volume":"120","author":"Villari","year":"2009","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1161\/01.CIR.79.4.744","article-title":"Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement","volume":"79","author":"Krayenbuehl","year":"1989","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1161\/01.CIR.76.1.77","article-title":"Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: A prospective two-dimensional echocardiographic study","volume":"76","author":"Sutton","year":"1987","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/ehjci\/jez049","article-title":"Time course of left ventricular remodeling and mechanics after aortic valve surgery: Aortic stenosis vs. aortic regurgitation","volume":"20","author":"Vollema","year":"2019","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"645693","DOI":"10.3389\/fcvm.2021.645693","article-title":"Assessment of 10-Year Left-Ventricular-Remodeling by CMR in Patients Following Aortic Valve Replacement","volume":"8","author":"Rank","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/ejcts\/ezab004","article-title":"Blunted beta-adrenoceptor-mediated inotropy in valvular cardiomyopathy: Another piece of the puzzle in human aortic valve disease","volume":"60","author":"Petersen","year":"2021","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nature01510","article-title":"From genomics to proteomics","volume":"422","author":"Tyers","year":"2003","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nbt1315","article-title":"Improving the success rate of proteome analysis by modeling protein-abundance distributions and experimental designs","volume":"25","author":"Eriksson","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF03256227","article-title":"Cardiovascular proteomics: Past, present, and future","volume":"11","author":"White","year":"2007","journal-title":"Mol. Diagn. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10557-015-6637-y","article-title":"Pharmacogenomics to Revive Drug Development in Cardiovascular Disease","volume":"30","author":"Tardif","year":"2016","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24389","DOI":"10.1038\/s41598-021-03907-3","article-title":"Proteomic mapping of atrial and ventricular heart tissue in patients with aortic valve stenosis","volume":"11","author":"Barbarics","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_18","unstructured":"R Development Core Team (2022). Vienna, Austria: R Foundation for Statistical Computing, R Development Core Team."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Hochberg","year":"1995","journal-title":"JR Stat. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"W193","DOI":"10.1093\/nar\/gkm226","article-title":"g:Profiler\u2014A web-based toolset for functional profiling of gene lists from large-scale experiments","volume":"35","author":"Reimand","year":"2007","journal-title":"Nucleic. Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1172\/JCI81870","article-title":"Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload","volume":"127","author":"Toischer","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1038\/s41467-017-01747-2","article-title":"Region and cell-type resolved quantitative proteomic map of the human heart","volume":"8","author":"Doll","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy","volume":"15","author":"Nakamura","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00428-021-03038-0","article-title":"Cardiac hypertrophy at autopsy","volume":"479","author":"Basso","year":"2021","journal-title":"Virchows Arch."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109828","DOI":"10.1016\/j.cellsig.2020.109828","article-title":"Adding insult to injury\u2014Inflammation at the heart of cardiac fibrosis","volume":"77","author":"Smolgovsky","year":"2021","journal-title":"Cell Signal"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1089\/ars.2013.5823","article-title":"Targeting the ubiquitin-proteasome system in heart disease: The basis for new therapeutic strategies","volume":"21","author":"Drews","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.bcp.2011.03.009","article-title":"MG132 treatment attenuates cardiac remodeling and dysfunction following aortic banding in rats via the NF-\u03baB\/TGF\u03b21 pathway","volume":"81","author":"Ma","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e012673","DOI":"10.1161\/JAHA.119.012673","article-title":"Glucose Metabolism in Cardiac Hypertrophy and Heart Failure","volume":"8","author":"Tran","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/CIRCRESAHA.121.318241","article-title":"Cardiac Energy Metabolism in Heart Failure","volume":"128","author":"Lopaschuk","year":"2021","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1023\/A:1007704817774","article-title":"Significance of the 5-phosphoribosyl-1-pyrophosphate pool for cardiac purine and pyrimidine nucleotide synthesis: Studies with ribose, adenine, inosine, and orotic acid in rats","volume":"12","author":"Zimmer","year":"1998","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Faller, K.M.E., Medway, D.J., Aksentijevi\u0107, D., Sebag-Montefiore, L., Schneider, J.E., Lygate, C.A., and Neubauer, S. (2013). Ribose Supplementation Alone or with Elevated Creatine Does Not Preserve High Energy Nucleotides or Cardiac Function in the Failing Mouse Heart. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066461"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1072828","DOI":"10.3389\/fcvm.2022.1072828","article-title":"Emerging MRI techniques for molecular and functional phenotyping of the diseased heart","volume":"9","author":"Cheng","year":"2022","journal-title":"Front. Cardiovasc. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/6\/878\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:52:49Z","timestamp":1760122369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/6\/878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,11]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cells12060878"],"URL":"https:\/\/doi.org\/10.3390\/cells12060878","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,11]]}}}