{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:47:06Z","timestamp":1790196426162,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veterans Affairs (VA) BLR&D Merit Award","award":["I01 BX003635"],"award-info":[{"award-number":["I01 BX003635"]}]},{"DOI":"10.13039\/100000005","name":"the Department of Defense","doi-asserted-by":"crossref","award":["PR200793"],"award-info":[{"award-number":["PR200793"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"the National Institutes of Health","doi-asserted-by":"crossref","award":["2U54GM115458"],"award-info":[{"award-number":["2U54GM115458"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Nebraska Medical Center College of Medicine"},{"name":"the National Institute of Occupational and Safety Health","award":["R01-OH012045"],"award-info":[{"award-number":["R01-OH012045"]}]},{"name":"Veterans Affairs (VA) BLR&D Merit Award","award":["I01 BX005687"],"award-info":[{"award-number":["I01 BX005687"]}]},{"name":"the National Institutes of Health\u2014NHLBI","award":["R01 HL172846"],"award-info":[{"award-number":["R01 HL172846"]}]},{"DOI":"10.13039\/100006260","name":"the Rheumatology Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Individuals with rheumatoid arthritis (RA) face increased cardiovascular mortality due to heart failure (HF) complications. Post-translational modifications, such as citrullination (CIT) and malondialdehyde\u2013acetaldehyde (MAA) adduction, are implicated in RA pathogenesis. However, their role in RA-associated HF is not well understood. This study examines the deposition of MAA and CIT in cardiac tissues of RA-HF patients and investigates how MAA and CIT adducts on fibrinogen (FIB-MAA-CIT) drive crosstalk between macrophages and endothelial cells in vitro. We demonstrated elevated MAA and CIT adducts, strong perivascular MAA-CIT co-localization, and increased perivascular collagen deposition in the myocardium of RA-HF patients compared to non-RA HF controls. Treating human coronary artery endothelial cells (HCAECs) with FIB-MAA-CIT induced upregulation of inflammatory markers including MCP-1, IL-6, ICAM-1, and VCAM-1 compared to unmodified FIB. This response was amplified when HCAECs were treated with cell culture media obtained from FIB-MAA-CIT-stimulated macrophages. FIB-MAA-CIT activation of macrophages engaged NF-\u03baB and p38 signaling pathways and inhibition of these pathways reduced FIB-MAA-CIT-mediated macrophage cytokine secretion and subsequent HCAEC responses. In summary, our findings support a novel mechanism by which endogenously modified proteins drive macrophage\u2013endothelial cell crosstalk, promoting myocardial inflammation. Targeting these post-translational modifications may present novel therapeutic strategies to mitigate HF in RA.<\/jats:p>","DOI":"10.3390\/cimb47110943","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:33:21Z","timestamp":1763141601000},"page":"943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Citrullinated and Malondialdehyde\u2013Acetaldehyde-Modified Fibrinogen Activates Macrophages and Promotes Coronary Endothelial Cell Inflammation"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0558-9286","authenticated-orcid":false,"given":"Wenxian","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2958-6444","authenticated-orcid":false,"given":"Hannah J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9104-2238","authenticated-orcid":false,"given":"Michael J.","family":"Duryee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozima","family":"Aripova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska 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C.","family":"Drvol","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason G.","family":"Feely","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-4157","authenticated-orcid":false,"given":"Tate M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-0840","authenticated-orcid":false,"given":"Mabruka","family":"Alfaidi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-0077","authenticated-orcid":false,"given":"Daniel R.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineeth K.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE 68198, 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