{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:51:06Z","timestamp":1787028666205,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KarRC RAS","award":["FMEN-2022-0017"],"award-info":[{"award-number":["FMEN-2022-0017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF) exhibit significant clinical and pathophysiological overlap, suggesting convergent molecular pathways driving fibrosis. This prospective longitudinal study investigates the sustained dysregulation of matrix metalloproteinases (MMP)-2 and MMP-9 and its relationship with evolving systemic inflammation and endothelial dysfunction in convalescent COVID-19 patients, with comparative analysis to IPF. Methods: We conducted a prospective observational study of 86 patients at 6 and 12 months post-SARS-CoV-2 infection, stratified by high-resolution CT evidence of PCPF (FB+ group, n = 32) or absence of fibrosis (FB\u2212 group, n = 54). Gene expression of MMP-2 and MMP-9 in peripheral blood leukocytes and circulating levels of MMP-2, MMP-9, pro-inflammatory cytokines (TNF-\u03b1, IL-6), and endothelial dysfunction markers (Endothelin-1 [ET-1], adhesion molecules) were quantified via qRT-PCR and ELISA. A pre-pandemic healthy control group (HD, n = 20) and an IPF patient group (n = 10) served as comparators. Results: A significant, sustained elevation of MMP-2 and MMP-9 was observed in all post-COVID-19 patients versus HDs, most pronounced in the FB+ group and qualitatively similar to IPF. A critical divergence emerged: FB\u2212 patients showed resolution of systemic inflammation (reduced TNF-\u03b1, IL-6), whereas FB+ patients exhibited persistent cytokine elevation. Critically, a delayed, severe endothelial dysfunction, characterized by a profound surge in ET-1 and elevated adhesion molecules, manifested exclusively in the FB+ cohort at 12 months. Positive correlations linked plasma MMP-2\/9 levels with ET-1 (rs = 0.65, p = 0.004; rs = 0.49, p = 0.009) and ET-1 with sICAM-1 (rs = 0.68, p = 0.01). Conclusions: The development of PCPF is associated with a distinct pathogenic triad: sustained MMP dysregulation, failure to resolve inflammation, and severe late-phase endothelial dysfunction. The correlative links between these components suggest a self-reinforcing loop. This systemic signature mirrors patterns in IPF, underscoring shared final pathways in fibrotic lung disease and identifying the MMP\u2013inflammation\u2013endothelial axis as a promising target for biomarker development and therapeutic intervention.<\/jats:p>","DOI":"10.3390\/jcm15020671","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dysregulation of MMP-2 and MMP-9 in Post-COVID-19 and IPF: Correlations with Systemic Inflammation and Endothelial Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-1089","authenticated-orcid":false,"given":"Olga V.","family":"Balan","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research, Karelian Research Centre of the Russian Academy of Sciences (KarRC RAS), 185910 Petrozavodsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-0218","authenticated-orcid":false,"given":"Irina E.","family":"Malysheva","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Karelian Research Centre of the Russian Academy of Sciences (KarRC RAS), 185910 Petrozavodsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5416-9536","authenticated-orcid":false,"given":"Ella L.","family":"Tikhonovich","sequence":"additional","affiliation":[{"name":"Respiratory Centre, Republic Hospital Named After V.A. Baranov, 185002 Petrozavodsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-7400","authenticated-orcid":false,"given":"Liudmila A.","family":"Lysenko","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Karelian Research Centre of the Russian Academy of Sciences (KarRC RAS), 185910 Petrozavodsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/s41591-022-01840-0","article-title":"Long COVID after breakthrough SARS-CoV-2 infection","volume":"28","author":"Bowe","year":"2022","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Comelli, A., Viero, G., Bettini, G., Nobili, A., Tettamanti, M., Galbussera, A.A., Muscatello, A., Mantero, M., Canetta, C., and Martinelli Boneschi, F. (2022). 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