{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:47:37Z","timestamp":1785764857167,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Direcci\u00f3n de Ciencia B\u00e1sica y de Frontera of the Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)-M\u00e9xico","award":["CBF-2025-815-I"],"award-info":[{"award-number":["CBF-2025-815-I"]}]},{"award":["CBF-2025-815-I"],"award-info":[{"award-number":["CBF-2025-815-I"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Emerging evidence suggests that deoxyribonucleic acid (DNA) methylation may be linked to progression from acute pulmonary embolism (APE) to chronic thromboembolic pulmonary hypertension (CTEPH), especially in genes regulating vascular tone. We investigated the association between tachykinin precursor 1 (TAC1) promoter methylation and the APE-to-CTEPH transition in a 6-month ambispective cohort study of 110 patients with confirmed APE. We recorded clinical, laboratory, and hemodynamic parameters at hospital admission and collected 4 mL of peripheral blood for DNA extraction. We quantified the percentage of TAC1 promoter methylation using bisulfite conversion and methylation-specific polymerase chain reaction (PCR), also assessing TAC1 gene expression by quantitative PCR. During the 6-month follow-up, 7.2% of patients developed CTEPH. Patients who later progressed to CTEPH had a significant 0.4-fold increase in TAC1 promoter methylation compared to those who did not. Increased methylation was associated with a 1.5-fold decrease in TAC1 gene expression in whole-blood leukocytes from CTEPH patients. TAC1 methylation significantly correlated with mixed venous oxygen saturation (SvO2), D-dimer, and B-type natriuretic peptide concentrations. TAC1 promoter hypermethylation is associated with progression from APE to CTEPH and concurs with TAC1 gene repression, probably compromising systemic oxygenation, thrombus resolution, and cardiac strain.<\/jats:p>","DOI":"10.3390\/ijms27156913","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methylation in the TAC1 Gene Promoter Is Associated with the Transition from Acute Pulmonary Embolism to Chronic Thromboembolic Pulmonary Hypertension"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-699X","authenticated-orcid":false,"given":"Leslie Marisol","family":"Gonz\u00e1lez-Hermosillo","sequence":"first","affiliation":[{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Unidad de Posgrado, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Laboratorio de Inmunometabolismo, Direcci\u00f3n de Investigaci\u00f3n, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Cueto-Robledo","sequence":"additional","affiliation":[{"name":"Urgencias Cardiorrespiratorias, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Ciudad de M\u00e9xico 06720, Mexico"},{"name":"Cl\u00ednica de Circulaci\u00f3n Pulmonar, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Ciudad de M\u00e9xico 06720, Mexico"},{"name":"Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Gaytan-Cervantes","sequence":"additional","affiliation":[{"name":"Laboratorio de Secuenciaci\u00f3n, Divisi\u00f3n de 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Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-7815","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Fragoso","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1, Tlalpan, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3961-0987","authenticated-orcid":false,"given":"Nallely","family":"Bueno-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Prote\u00f3mica y Metabol\u00f3mica, Direcci\u00f3n de Investigaci\u00f3n, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Ciudad de M\u00e9xico 06720, 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