{"id":"b76115c0faf1","type":"article","url":"https://hartvaat.nl/2022/02/10/propionaat-vermindert-atherosclerose-via-immuunregulatie-van-intestinaal-cholest/","title":"Propionaat vermindert atherosclerose via immuunregulatie van intestinaal cholesterolmetabolisme","title_en":"Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","internist"],"tags":["dyslipidemie","ezetimibe","pcsk9-remmers","statines"],"journal":"European heart journal","doi":"10.1093/eurheartj/ehab644","source_url":"https://doi.org/10.1093/eurheartj/ehab644","authors":["Arash Haghikia","Friederike Zimmermann","Paul Schumann","Andrzej Jasina","Johann Roessler","David Schmidt","Philipp Heinze","Johannes Kaisler","Vanasa Nageswaran","Annette Aigner","Uta Ceglarek","Roodline Cineus","Ahmed N Hegazy","Emiel P C van der Vorst","Yvonne Döring","Christopher M Strauch","Ina Nemet","Valentina Tremaroli","Chinmay Dwibedi","Nicolle Kränkel","David M Leistner","Markus M Heimesaat","Stefan Bereswill","Geraldine Rauch","Ute Seeland","Oliver Soehnlein","Dominik N Müller","Ralf Gold","Fredrik Bäckhed","Stanley L Hazen","Aiden Haghikia","Ulf Landmesser"],"significance":6,"published":"2022-02-10","source_date":"2022-02-10","image":"","kennis":[],"congress":"","summary_en":"This study demonstrated that propionate, a short-chain fatty acid produced by gut bacteria, attenuates atherosclerosis through immune-dependent regulation of intestinal cholesterol metabolism, advancing the microbiome-cardiovascular connection.","created":"2026-07-03T10:29:38Z","updated":"2026-07-03T13:28:45Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Studie die aantoont dat propionaat (korte-keten vetzuur) atherosclerose vermindert via immuun-afhankelijke regulatie van intestinaal cholesterolmetabolisme.","abstract_original":"AIMS: 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. METHODS AND RESULTS: Using 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. CONCLUSION: Our 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."}