{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:21:54Z","timestamp":1766035314727,"version":"3.48.0"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF21OC0067235"],"award-info":[{"award-number":["NNF21OC0067235"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"crossref","award":["LONG-COVID-EXP-CM"],"award-info":[{"award-number":["LONG-COVID-EXP-CM"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Post-COVID cardiac complications have emerged as a significant and persistent clinical concern, yet their underlying mechanisms remain poorly understood. Animal models can act as proxies to investigate the pathophysiology of the human, post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this experimental study was to evaluate the expression of inflammatory biomarkers in cardiac tissue 28 days after SARS-CoV-2 infection in a female hACE2 mouse model, with a focus on chemokine-mediated immune activation. Twelve female C57BL\/6 hACE2 mice were infected with the Omicron variant (BA.1.17 lineage) of SARS-CoV-2, and eleven non-infected mice served as controls. Cardiac tissue was analyzed via Western blot for markers of innate immune activation (TLR4, MyD88, NF-\u03baB) and pro-inflammatory cytokines (IL-6, IL-18, IL-1\u03b2, TNF-\u03b1, CD11d). Cardiac tissue injury markers (iNOS, PAI-1 and Connexin43) were also analyzed. Compared to non-infected mice, cardiac tissue from infected mice showed significantly higher expression of IL-6 (p = 0.028), indicating an inflammatory state, and CD11d (p = 0.016), suggesting an inflammatory stage accompanied by sustained activation of chemokine-mediated inflammatory signaling. No significant differences in TLR4 (p = 0.340), MyD88 (p = 0.410), NF-\u03baB p65 (p = 0.780), IL-18 (p = 0.548), IL-1\u03b2 (p = 0.455), and TNF-\u03b1 (p = 0.125) expressions were observed Similarly, no changes in cardiac damage markers (iNOS: p = 0.4684; PAI-1: p = 0.5345; Connexin 43: p = 0.2879) were found. The results of this experimental study would support the hypothesis of persistent low-grade inflammation as a contributor to post-COVID cardiac sequelae in females that is not accompanied by severe tissue damage, as also observed in clinical studies. This study also reinforces the need for studies evaluating the functional and structural evolution of the myocardium after an acute SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/v17121629","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:41:12Z","timestamp":1765899672000},"page":"1629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac Tissue Damage in a Female Animal Post-COVID Model: Relevance of Chemokine-Mediated Inflammation"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6583-4587","authenticated-orcid":false,"given":"Silvia","family":"Flaj-Prados","sequence":"first","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-6283","authenticated-orcid":false,"given":"Esperanza","family":"Herrad\u00f3n Pliego","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-6934","authenticated-orcid":false,"given":"Carlos","family":"Goicoechea Garcia","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-2750","authenticated-orcid":false,"given":"Eva M.","family":"S\u00e1nchez-Robles","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1579","authenticated-orcid":false,"given":"Lars","family":"Arendt-Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"},{"name":"Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-9690","authenticated-orcid":false,"given":"C\u00e9sar","family":"Fern\u00e1ndez-de-las-Pe\u00f1as","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-0387","authenticated-orcid":false,"given":"Visitaci\u00f3n","family":"L\u00f3pez-Miranda","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del 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