{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:42:23Z","timestamp":1784241743455,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agencia Estatal de Investigaci\u00f3n, Spain","award":["PID2019-109369RB-I0"],"award-info":[{"award-number":["PID2019-109369RB-I0"]}]},{"name":"Fundaci\u00f3n Salud 2000 - Merck Serono","award":["Beca de Investigaci\u00f3n 2013"],"award-info":[{"award-number":["Beca de Investigaci\u00f3n 2013"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/01374"],"award-info":[{"award-number":["PI14\/01374"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00508"],"award-info":[{"award-number":["PI17\/00508"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n, Spain","award":["RTI2018-095569-B-I00"],"award-info":[{"award-number":["RTI2018-095569-B-I00"]}]},{"DOI":"10.13039\/501100006541","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["Programa de Garant\u00eda Juvenil 2018"],"award-info":[{"award-number":["Programa de Garant\u00eda Juvenil 2018"]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Cerveza y Salud","award":["Beca Manuel de Oya de Investigaci\u00f3n"],"award-info":[{"award-number":["Beca Manuel de Oya de Investigaci\u00f3n"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diet is a well-known risk factor of cardiovascular diseases (CVDs). Some microRNAs (miRNAs) have been described to regulate molecular pathways related to CVDs. Diet can modulate miRNAs and their target genes. Choline, betaine, and l-carnitine, nutrients found in animal products, are metabolized into trimethylamine n-oxide (TMAO), which has been associated with CVD risk. The aim of this study was to investigate TMAO regulation of CVD-related miRNAs and their target genes in cellular models of liver and macrophages. We treated HEPG-2, THP-1, mouse liver organoids, and primary human macrophages with 6 \u00b5M TMAO at different timepoints (4, 8, and 24 h for HEPG-2 and mouse liver organoids, 12 and 24 h for THP-1, and 12 h for primary human macrophages) and analyzed the expression of a selected panel of CVD-related miRNAs and their target genes and proteins by real-time PCR and Western blot, respectively. HEPG-2 cells were transfected with anti-miR-30c and syn-miR-30c. TMAO increased the expression of miR-21-5p and miR-30c-5p. PER2, a target gene of both, decreased its expression with TMAO in HEPG-2 and mice liver organoids but increased its mRNA expression with syn-miR-30c. We concluded that TMAO modulates the expression of miRNAs related to CVDs, and that such modulation affects their target genes.<\/jats:p>","DOI":"10.3390\/ijms222011145","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T13:45:17Z","timestamp":1634564717000},"page":"11145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Trimethylamine n-Oxide (TMAO) Modulates the Expression of Cardiovascular Disease-Related microRNAs and Their Targets"],"prefix":"10.3390","volume":"22","author":[{"given":"Laura","family":"D\u00edez-Ricote","sequence":"first","affiliation":[{"name":"Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Ruiz-Valderrey","sequence":"additional","affiliation":[{"name":"Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Mic\u00f3","sequence":"additional","affiliation":[{"name":"Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Blanco-Rojo","sequence":"additional","affiliation":[{"name":"Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"},{"name":"Research and Development Department, Biosearch Life, 18004 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3597-9234","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Tom\u00e9-Carneiro","sequence":"additional","affiliation":[{"name":"Bioactive Food Ingredients Group, Precision Nutrition and Cardiometabolic Health Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"D\u00e1valos","sequence":"additional","affiliation":[{"name":"Epigenetics of Lipid Metabolism Group, Precision Nutrition and Cardiometabolic Health Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Ordov\u00e1s","sequence":"additional","affiliation":[{"name":"Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"},{"name":"Nutrition and Genomics Laboratory, JM_USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-6629","authenticated-orcid":false,"given":"Lidia","family":"Daimiel","sequence":"additional","affiliation":[{"name":"Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, UAM + CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics\u20142020 Update: A Report From the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","unstructured":"Eurostat (2021, May 05). 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