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Inflammation is a major contributor to atherosclerosis development and progression. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting Protein 2) or inhibition of the matrix metallopeptidase (MMP) regulator RECK (REversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to pro-oxidant, proinflammatory, pro-mitogenic and pro-migratory effects in response to external stimuli in vascular smooth muscle cells. Here we hypothesized that EF24, a curcumin analog with a better bioavailability and bioactivity profile, reverses interleukin (IL)-18-induced TRAF3IP2 induction, RECK suppression and the proinflammatory phenotype of primary human aortic smooth muscle cells (ASMC). The exposure of ASMC to functionally active recombinant human IL-18 (10 ng\/mL) upregulated TRAF3IP2 mRNA and protein expression, but markedly suppressed RECK in a time-dependent manner. Further investigations revealed that IL-18 inhibited both miR-30a and miR-342 in a p38 MAPK- and JNK-dependent manner, and while miR-30a mimic blunted IL-18-induced TRAF3IP2 expression, miR-342 mimic restored RECK expression. Further, IL-18 induced ASMC migration, proliferation and proinflammatory phenotype switching, and these effects were attenuated by TRAF3IP2 silencing, and the forced expression of RECK or EF24. Together, these results suggest that the curcumin analog EF24, either alone or as an adjunctive therapy, has the potential to delay the development and progression of atherosclerosis and other vascular inflammatory and proliferative diseases by differentially regulating TRAF3IP2 and RECK expression in ASMC.<\/jats:p>","DOI":"10.3390\/cells13201673","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T07:53:05Z","timestamp":1728546785000},"page":"1673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["EF24, a Curcumin Analog, Reverses Interleukin-18-Induced miR-30a or miR-342-Dependent TRAF3IP2 Expression, RECK Suppression, and the Proinflammatory Phenotype of Human Aortic Smooth Muscle Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1956-0182","authenticated-orcid":false,"given":"Yusuke","family":"Higashi","sequence":"first","affiliation":[{"name":"Medicine\/Cardiology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Dashek","sequence":"additional","affiliation":[{"name":"NextGen Precision Health, University of Missouri, Columbia, MO 65211, USA"},{"name":"Comparative Medicine Program, University of Missouri, Columbia, MO 65211, USA"},{"name":"Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-3617","authenticated-orcid":false,"given":"Patrice","family":"Delafontaine","sequence":"additional","affiliation":[{"name":"Medicine\/Cardiology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy Scott","family":"Rector","sequence":"additional","affiliation":[{"name":"NextGen Precision Health, University of Missouri, Columbia, MO 65211, USA"},{"name":"Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65201, USA"},{"name":"Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bysani","family":"Chandrasekar","sequence":"additional","affiliation":[{"name":"Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA"},{"name":"Department of Medicine, Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO 65201, USA"},{"name":"Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65201, USA"},{"name":"Dalton Cardiovascular Center, University of Missouri, Columbia, MO 65203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/j.jacc.2019.08.012","article-title":"From Subclinical Atherosclerosis to Plaque Progression and Acute Coronary Events: JACC State-of-the-Art Review","volume":"74","author":"Ahmadi","year":"2019","journal-title":"J. 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