{"entity": "researcher", "timestamp": "2026-07-12T00:28:02.667Z", "family": "Haghikia", "given": "Arash", "initials": "A", "orcid": "0000-0002-5646-3237", "affiliations": ["Department of Cardiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.", "German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.", "Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Stra\u03b2e 2, Berlin 10178, Germany."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/25d47cc07b304007b13eea2f0adebf5d.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/25d47cc07b304007b13eea2f0adebf5d"}}, "publications": [{"entity": "publication", "iuid": "278827f8e9f14ad385af87cd8a8bf4f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/278827f8e9f14ad385af87cd8a8bf4f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/278827f8e9f14ad385af87cd8a8bf4f5"}}, "title": "Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.", "authors": [{"family": "Haghikia", "given": "Arash", "initials": "A", "orcid": "0000-0002-5646-3237", "researcher": {"href": "https://publications.scilifelab.se/researcher/25d47cc07b304007b13eea2f0adebf5d.json"}}, {"family": "Zimmermann", "given": "Friederike", "initials": "F", "orcid": "0000-0002-4353-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac424ea1029f44c685fdf99934a28588.json"}}, {"family": "Schumann", "given": "Paul", "initials": "P", "orcid": "0000-0001-7961-0749", "researcher": {"href": "https://publications.scilifelab.se/researcher/eec3fab5a9704ef4a60b44c047f79b9a.json"}}, {"family": "Jasina", "given": "Andrzej", "initials": "A"}, {"family": "Roessler", "given": "Johann", "initials": "J"}, {"family": "Schmidt", "given": "David", "initials": "D", "orcid": "0000-0002-3779-6765", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2f6de49b07d410cb62d3e957d41dbc9.json"}}, {"family": "Heinze", "given": "Philipp", "initials": "P"}, {"family": "Kaisler", "given": "Johannes", "initials": "J", "orcid": "0000-0003-1753-700X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a711e7bf911b4ab298d26b6b45d96bba.json"}}, {"family": "Nageswaran", "given": "Vanasa", "initials": "V"}, {"family": "Aigner", "given": "Annette", "initials": "A", "orcid": "0000-0003-4891-8921", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc501331234a48dbbffb2588dc47ec40.json"}}, {"family": "Ceglarek", "given": "Uta", "initials": "U", "orcid": "0000-0002-4034-5535", "researcher": {"href": "https://publications.scilifelab.se/researcher/77439f686ffb41d79ffe38e0794d49ce.json"}}, {"family": "Cineus", "given": "Roodline", "initials": "R", "orcid": "0000-0003-4393-5757", "researcher": {"href": "https://publications.scilifelab.se/researcher/66d89006dc2440efba422606042e7646.json"}}, {"family": "Hegazy", "given": "Ahmed N", "initials": "AN", "orcid": "0000-0002-2946-8251", "researcher": {"href": "https://publications.scilifelab.se/researcher/873d36abaae94c9e8da92dddb7c3fed4.json"}}, {"family": "van der Vorst", "given": "Emiel P C", "initials": "EPC", "orcid": "0000-0001-5771-6278", "researcher": {"href": "https://publications.scilifelab.se/researcher/afb3f99e22844d87bd2dab067a8c6c22.json"}}, {"family": "D\u00f6ring", "given": "Yvonne", "initials": "Y"}, {"family": "Strauch", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-4766-9604", "researcher": {"href": "https://publications.scilifelab.se/researcher/94ad120405244d1d882f1d77e33508d3.json"}}, {"family": "Nemet", "given": "Ina", "initials": "I", "orcid": "0000-0002-0657-7121", "researcher": {"href": "https://publications.scilifelab.se/researcher/c792cffaa9d841caa7ad8ee768c3f745.json"}}, {"family": "Tremaroli", "given": "Valentina", "initials": "V"}, {"family": "Dwibedi", "given": "Chinmay", "initials": "C"}, {"family": "Kr\u00e4nkel", "given": "Nicolle", "initials": "N", "orcid": "0000-0002-9363-1770", "researcher": {"href": "https://publications.scilifelab.se/researcher/2cefd29daaa84c7d91db84b42c45b14d.json"}}, {"family": "Leistner", "given": "David M", "initials": "DM", "orcid": "0000-0002-4351-420X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c17a728e2c5d4efeb4ba56cf759e65e5.json"}}, {"family": "Heimesaat", "given": "Markus M", "initials": "MM", "orcid": "0000-0001-6399-651X", "researcher": {"href": "https://publications.scilifelab.se/researcher/126c6d4143dd4defa72060e18622fe2d.json"}}, {"family": "Bereswill", "given": "Stefan", "initials": "S"}, {"family": "Rauch", "given": "Geraldine", "initials": "G"}, {"family": "Seeland", "given": "Ute", "initials": "U"}, {"family": "Soehnlein", "given": "Oliver", "initials": "O"}, {"family": "M\u00fcller", "given": "Dominik N", "initials": "DN"}, {"family": "Gold", "given": "Ralf", "initials": "R"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-4871-8818", "researcher": {"href": "https://publications.scilifelab.se/researcher/1689878e0c5542d08d3e2d5043a6ce5c.json"}}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Haghikia", "given": "Aiden", "initials": "A"}, {"family": "Landmesser", "given": "Ulf", "initials": "U", "orcid": "0000-0002-0214-3203", "researcher": {"href": "https://publications.scilifelab.se/researcher/49393c5b978546bda0232a7ecb2c83bf.json"}}], "type": "journal article", "published": "2022-02-10", "journal": {"title": "Eur. Heart J.", "issn": "1522-9645", "volume": "43", "issue": "6", "pages": "518-533", "issn-l": "0195-668X"}, "abstract": "Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism.\n\nUsing both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels.\n\nOur findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.", "doi": "10.1093/eurheartj/ehab644", "pmid": "34597388", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9097250"}, {"db": "pii", "key": "6379035"}, {"db": "ClinicalTrials.gov", "key": "NCT03590496"}], "notes": [], "created": "2023-11-27T21:52:01.623Z", "modified": "2024-01-16T13:48:37.507Z"}]}