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Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1\/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKC\u03b2) as a critical mediator of this pathway and demonstrate that the PKC\u03b2 inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKC\u03b2 and ERK1\/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.<\/jats:p>","DOI":"10.7554\/elife.08648","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T08:30:13Z","timestamp":1445934613000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.08648","source":"Crossref","is-referenced-by-count":110,"title":["A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome"],"prefix":"10.7554","volume":"4","author":[{"given":"Jefferson J","family":"Doyle","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States"},{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United 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