{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:51:14Z","timestamp":1755798674422,"version":"3.44.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Monocyte chemoattractant protein 1 (MCP-1) plays a critical role in the transmigration of peripheral monocytes, a central mechanism underlying chronic inflammation. In this study, we investigate postoperative serum kinetics of MCP-1 as a potential contributor to postoperative neurocognitive decline, arteriosclerosis, and the development of organ failures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy-one patients undergoing elective cardiac surgery were included in this study. Serum samples were collected preoperatively (t<jats:sub>baseline<\/jats:sub>), and postoperatively at 24\u202fh (t<jats:sub>24h<\/jats:sub>), 7\u202fdays (t<jats:sub>7d<\/jats:sub>), and 3\u202fmonths (t<jats:sub>3m<\/jats:sub>). MCP-1 levels were quantified in conjunction with other inflammatory markers and alarmins. Whole blood samples underwent lipopolysaccharide (LPS) stimulation to evaluate MCP-1 production capacity, and peripheral monocyte transcriptomes were analyzed. Surrogate markers of end-organ dysfunction, including markers of neurodegeneration, neuroinjury, vasculitis, and atherosclerosis, were assessed. Acute kidney failure was defined per the RIFLE criteria, and occurrences of cerebrovascular accidents (CVA), pulmonary embolism (PE), deep venous thrombosis (DVT), and dispositions were documented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cardiac surgery resulted in an acute increase in serum MCP-1 at 24\u202fh, 7\u202fdays, and 3\u202fmonths as compared to the presurgical baseline. MCP-4 levels were unchanged, while Regulated on Activation Normal T Cell Expressed and Secreted cytokine (RANTES) was significantly depleted after surgery. Except for a prior history of cerebrovascular accidents, other preoperative clinical conditions, duration of anesthesia, surgery, cross-clamp, estimated fluid loss, and transfusions did not influence t<jats:sub>24h<\/jats:sub> MCP-1 serum level. Perioperative use of non-steroidal anti-inflammatory drugs and opioids affected acute serum MCP-1 levels. At 3\u202fmonths, patients undergoing coronary artery bypass graft (CABG) surgery exhibited the most pronounced elevation in MCP-1 compared to other cardiac surgery. Serum IL-6 at 24\u202fh positively correlated with MCP-1 levels measured at 24\u202fh, 7\u202fdays, and 3\u202fmonths. Additionally, markers of neurodegeneration (<jats:italic>\u03c4<\/jats:italic> protein and amyloid <jats:italic>\u03b2<\/jats:italic>-1-40), some vascular inflammation (FGF-23 and FGF-21), and atherosclerosis (LOX-1) demonstrated correlational relationships with MCP-1. Finally, patients experiencing postoperative cerebrovascular accidents demonstrated depressed levels of MCP-1 at 24\u202fh, 7\u202fdays, and 3\u202fmonths as compared to patients recovering uneventfully.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum MCP-1 levels were elevated for up to 3\u202fmonths following cardiac surgery, even in patients who experienced an uneventful recovery. MCP-4 was unchanged, while RANTES depressed post-surgery. A significant correlation between MCP-1 and serum surrogate markers of brain injury, vascular inflammation, and atherosclerosis highlights MCP-1 as a potential biomarker and a possible mediator of adverse outcomes after cardiac surgery.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1561886","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:01:16Z","timestamp":1755597676000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated serum levels of monocyte chemoattractant protein-1 in 71 patients 3\u202fmonths after elective cardiac surgery suggest a potential link to persistent inflammation but not an increased propensity for perioperative cerebrovascular events"],"prefix":"10.3389","volume":"12","author":[{"given":"Krzysztof","family":"Laudanski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Antar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossam","family":"Gad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Diedrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP-1: function, regulation, and involvement in disease","volume":"101","author":"Singh","year":"2021","journal-title":"Int 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RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension","volume":"30","author":"Mikolajczyk","year":"2016","journal-title":"FASEB J"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/S0009-9120(99)00038-7","article-title":"RANTES and MCP-1 chemokine plasma levels in chronic renal transplant dysfunction and chronic renal failure","volume":"32","author":"Corsi","year":"1999","journal-title":"Clin Biochem"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/S0305-4179(03)00070-6","article-title":"Monocyte chemoattractant protein-1 (MCP-1) and macrophage infiltration into the skin after burn injury in aged mice","volume":"29","author":"Shallo","year":"2003","journal-title":"Burns"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/path.877","article-title":"Potential role for monocyte chemotactic protein-4 (MCP-4) in monocyte\/macrophage 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