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Herein, we investigated the effects of linoleic acid (LA) as \u03c9\u20106 PUFA, eicosapentaenoic acid (EPA) as \u03c9\u20103 PUFA and palmitic acid (PA) on vasculogenesis of embryonic stem (ES) cells. LA and EPA increased vascular structure formation and protein expression of the endothelial\u2010specific markers fetal liver kinase\u20101, CD31 as well as VE\u2010cadherin, whereas PA was without effect. LA and EPA increased reactive oxygen species (ROS) and nitric oxide (NO), activated endothelial NO synthase (eNOS) and raised intracellular calcium. The calcium response was inhibited by the intracellular calcium chelator BAPTA, sulfo\u2010N\u2010succinimidyl oleate which is an antagonist of CD36, the scavenger receptor for fatty acid uptake as well as by a CD36 blocking antibody. Prevention of ROS generation by radical scavengers or the NADPH oxidase inhibitor VAS2870 and inhibition of eNOS by L\u2010NAME blunted vasculogenesis. PUFAs stimulated AMP activated protein kinase\u2010\u03b1 (AMPK\u2010\u03b1) as well as peroxisome proliferator\u2010activated receptor\u2010\u03b1 (PPAR\u2010\u03b1). AMPK activation was abolished by calcium chelation as well as inhibition of ROS and NO generation. Moreover, PUFA\u2010induced vasculogenesis was blunted by the PPAR\u2010\u03b1 inhibitor GW6471. In conclusion, \u03c9\u20103 and \u03c9\u20106 PUFAs stimulate vascular differentiation of ES cells via mechanisms involving calcium, ROS and NO, which regulate function of the energy sensors AMPK and PPAR\u2010\u03b1 and determine the metabolic signature of vascular cell differentiation.<\/jats:p>","DOI":"10.1002\/jcp.29606","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T09:20:05Z","timestamp":1580894405000},"page":"7094-7106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Omega\u20103 and Omega\u20106 polyunsaturated fatty acids stimulate vascular differentiation of mouse embryonic stem cells"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7665-0574","authenticated-orcid":false,"given":"Amer","family":"Taha","sequence":"first","affiliation":[{"name":"Department of Physiology Justus Liebig University Giessen  Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-1805","authenticated-orcid":false,"given":"Fatemeh","family":"Sharifpanah","sequence":"additional","affiliation":[{"name":"Department of Physiology Justus Liebig University Giessen  Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Wartenberg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Clinic of Internal Medicine I, University Heart Center Jena University Hospital  Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9144-4728","authenticated-orcid":false,"given":"Heinrich","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Physiology Justus Liebig University Giessen  Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"e_1_2_9_2_1","article-title":"Omega\u20103 fatty acids for the primary and secondary prevention of cardiovascular disease","volume":"7","author":"Abdelhamid A. 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