Cellular and extracellular proteomic profiling of paradoxical low-flow low-gradient aortic stenosis myocardium.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39355352", "kind": "science-record", "revision": 3, "content_hash": "sha256:d70ba29f2aa414c422653ea5670c9db042db9f55ad1f402f2abb9cc33d7db2ea", "created_at": "2026-11-01T20:29:33Z", "updated_at": "2026-11-01T22:12:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cellular and extracellular proteomic profiling of paradoxical low-flow low-gradient aortic stenosis myocardium.", "doi": "10.3389/fcvm.2024.1398114", "pmid": "39355352", "authors": ["Manar Elkenani", "Javier Barallobre-Barreiro", "Moritz Schnelle", "Belal A Mohamed", "Bo E Beuthner", "Christoph Friedemann Jacob", "Niels B Paul", "Xiaoke Yin", "Konstantinos Theofilatos", "Andreas Fischer", "Miriam Puls", "Elisabeth M Zeisberg", "Ajay M Shah", "Manuel Mayr", "Gerd Hasenfuß", "Karl Toischer"], "journal": "Frontiers in cardiovascular medicine", "year": 2024, "abstract": "Aims: Patients with severe aortic stenosis (AS), low transvalvular flow (LF) and low gradient (LG) with normal ejection fraction (EF)-are referred to as paradoxical LF-LG AS (PLF-LG). PLF-LG patients develop more advanced heart failure symptoms and have a worse prognosis than patients with normal EF and high-gradient AS (NEF-HG). Despite its clinical relevance, the mechanisms underlying PLF-LG are still poorly understood.\nMethods: Left ventricular (LV) myocardial biopsies of PLF-LG (n = 5) and NEF-HG patients (n = 6), obtained during transcatheter aortic valve implantation, were analyzed by LC-MS/MS after sequential extraction of cellular and extracellular matrix (ECM) proteins using a three-step extraction method. Proteomic data are available via ProteomeXchange with identifier PXD055391.\nResults: 73 cellular proteins were differentially abundant between the 2 groups. Among these, a network of proteins related to muscle contraction and arrhythmogenic cardiomyopathy (e.g., cTnI, FKBP1A and CACNA2D1) was found in PLF-LG. Extracellularly, upregulated proteins in PLF-LG were related to ATP synthesis and oxidative phosphorylation (e.g., ATP5PF, COX5B and UQCRB). Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p < 0.05). Consistently, immunohistochemical analysis confirmed its extracellular localization in PLF-LG AS LV sections along with an increase in its receptor, CD147, compared to the NEF-HG AS patients. Levels of core ECM proteins, namely collagens and proteoglycans, were comparable between groups.\nConclusion: Our study pinpointed novel candidates and processes with potential relevance in the pathophysiology of PLF-LG. The role of CyPA in particular warrants further investigation.", "claims": [{"id": "claim-method", "statement": "Two-tailed unpaired Student's t-test and Fisher's exact test were used where appropriate.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39355352", "locator": "sections[7] \"Statistical analysis\" paragraph 2", "quote": "Two-tailed unpaired Student's t-test and Fisher's exact test were used where appropriate."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data presented in the study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD055391 and 10.6019/PXD055391.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39355352", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The mass spectrometry proteomics data presented in the study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD055391 and 10.6019/PXD055391."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Cyclophilin A was increased in the extracellular extracts of PLF-LG AS patients by 1.3-fold compared with NEF-HG patients.", "kind": "quantitative", "target": {"value": 1.3, "unit": "fold change", "tolerance": null, "source": "Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p < 0.05)."}, "evidence": [{"asset": "source:pmid:39355352", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Cyclophilin A was increased in the extracellular extracts of PLF-LG AS patients by 1.3-fold compared with NEF-HG patients.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39355352"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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