{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:23:57Z","timestamp":1790126637210,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,22]],"date-time":"2023-01-22T00:00:00Z","timestamp":1674345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Propionic Acidemia Foundation","award":["PAF107"],"award-info":[{"award-number":["PAF107"]}]},{"name":"Propionic Acidemia Foundation","award":["PAF113"],"award-info":[{"award-number":["PAF113"]}]},{"name":"Propionic Acidemia Foundation","award":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"Spanish Ministry of Science and Innovation and European Regional Development Fund (Fondos Feder)","award":["PAF107"],"award-info":[{"award-number":["PAF107"]}]},{"name":"Spanish Ministry of Science and Innovation and European Regional Development Fund (Fondos Feder)","award":["PAF113"],"award-info":[{"award-number":["PAF113"]}]},{"name":"Spanish Ministry of Science and Innovation and European Regional Development Fund (Fondos Feder)","award":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"Fundaci\u00f3n Ram\u00f3n Areces (XX National Call 2020)","award":["PAF107"],"award-info":[{"award-number":["PAF107"]}]},{"name":"Fundaci\u00f3n Ram\u00f3n Areces (XX National Call 2020)","award":["PAF113"],"award-info":[{"award-number":["PAF113"]}]},{"name":"Fundaci\u00f3n Ram\u00f3n Areces (XX National Call 2020)","award":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Propionic acidemia (PA) disorder shows major involvement of the heart, among other alterations. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is driven mainly by the accumulation of toxic metabolites. To contribute to the elucidation of the mechanistic basis underlying this dysfunction, we have successfully generated cardiomyocytes through the differentiation of induced pluripotent stem cells (iPSCs) from a PCCB patient and its isogenic control. In this human cellular model, we aimed to examine microRNAs (miRNAs) profiles and analyze several cellular pathways to determine miRNAs activity patterns associated with PA cardiac phenotypes. We have identified a series of upregulated cardiac-enriched miRNAs and alterations in some of their regulated signaling pathways, including an increase in the expression of cardiac damage markers and cardiac channels, an increase in oxidative stress, a decrease in mitochondrial respiration and autophagy; and lipid accumulation. Our findings indicate that miRNA activity patterns from PA iPSC-derived cardiomyocytes are biologically informative and advance the understanding of the molecular mechanisms of this rare disease, providing a basis for identifying new therapeutic targets for intervention strategies.<\/jats:p>","DOI":"10.3390\/ijms24032182","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dysregulated Cell Homeostasis and miRNAs in Human iPSC-Derived Cardiomyocytes from a Propionic Acidemia Patient with Cardiomyopathy"],"prefix":"10.3390","volume":"24","author":[{"given":"Mar","family":"\u00c1lvarez","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1785-4988","authenticated-orcid":false,"given":"Pedro","family":"Ruiz-Sala","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3190-1958","authenticated-orcid":false,"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-3323","authenticated-orcid":false,"given":"Lourdes Ruiz","family":"Desviat","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-1417","authenticated-orcid":false,"given":"Eva","family":"Richard","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,22]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C.R., Beaudet, A.L., Sly, W., and Valle, D. 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