{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:50:42Z","timestamp":1789887042497,"version":"4.0.1"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T00:00:00Z","timestamp":1539907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente)","award":["number BIO33-2014: 2607452; BIO35-2015: 2617756; BIO37-2016: 2613074; BIO37-2017: 2631213; MPP1.2A-2018: 2634597"],"award-info":[{"award-number":["number BIO33-2014: 2607452; BIO35-2015: 2617756; BIO37-2016: 2613074; BIO37-2017: 2631213; MPP1.2A-2018: 2634597"]}]},{"name":"Italian Ministry of Health","award":["\u201c5 \u00d7 1000\u201d tax (2013 and 2014)"],"award-info":[{"award-number":["\u201c5 \u00d7 1000\u201d tax (2013 and 2014)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism has been associated with increased susceptibility to develop mood disorders and recently it has been also linked with cardiovascular disease (CVD). Interestingly, stressful conditions unveil the anxious\/depressive-like behavioral phenotype in heterozygous BDNFVal66Met (BDNFVal\/Met) mice, suggesting an important relationship in terms of gene-environment interaction (GxE). However, the interplay between stress and BDNFVal\/Met in relation to CVD is completely unknown. Here, we showed that BDNFVal\/Met mice display a greater propensity to arterial thrombosis than wild type BDNFVal\/Val mice after 7 days of restraint stress (RS). RS markedly increased the number of leukocytes and platelets, and induced hyper-responsive platelets as showed by increased circulating platelet\/leukocyte aggregates and enhanced expression of P-selectin and GPIIbIIIa in heterozygous mutant mice. In addition, stressed BDNFVal\/Met mice had a greater number of large and reticulated platelets but comparable number and maturation profile of bone marrow megakaryocytes compared to BDNFVal\/Val mice. Interestingly, RS led to a significant reduction of BDNF expression accompanied by an increased activity of tissue factor in the aorta of both BDNFVal\/Val and BDNFVal\/Met mice. In conclusion, we provide evidence that sub-chronic stress unveils prothrombotic phenotype in heterozygous BDNF Val66Met mice affecting both the number and functionality of blood circulating cells, and the expression of key thrombotic molecules in aorta. Human studies will be crucial to understand whether this GxE interaction need to be taken into account in risk stratification of coronary artery disease (CAD) patients.<\/jats:p>","DOI":"10.3390\/ijms19103235","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T10:08:02Z","timestamp":1539943682000},"page":"3235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sub-Chronic Stress Exacerbates the Pro-Thrombotic Phenotype in BDNFVal\/Met Mice: Gene-Environment Interaction in the Modulation of Arterial Thrombosis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-8016","authenticated-orcid":false,"given":"Leonardo","family":"Sandrini","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"},{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-7695","authenticated-orcid":false,"given":"Alessandro","family":"Ieraci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-2778","authenticated-orcid":false,"given":"Patrizia","family":"Amadio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9378-8874","authenticated-orcid":false,"given":"Fabrizio","family":"Veglia","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Popoli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tremoli","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7486-2637","authenticated-orcid":false,"given":"Silvia Stella","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/ajh\/hpv047","article-title":"State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease","volume":"28","author":"Cohen","year":"2015","journal-title":"Am. 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