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Abnormal variations in hemodynamic stress incite pathological EC transformation and inflammatory zone formation, ultimately leading to destruction of the vascular wall and aneurysm dilation. Hemodynamic stress activates key molecular pathways that result in the upregulation of chemotactic cytokines and adhesion molecules, leading to inflammatory cell recruitment and infiltration. Concurrently, oxidative stress damages EC-to-EC junction proteins, resulting in interendothelial gap formation. This further promotes leukocyte traffic into the vessel wall and the release of matrix metalloproteinases, which propagates vascular remodeling and breakdown. Abnormal hemodynamic stress and inflammation also trigger adverse changes in NOS activity, altering proper EC mediation of vascular tone and the local inflammatory environment. Additionally, the vasoprotective hormone estrogen modulates gene expression that often suppresses these harmful processes. Crosstalk between these sophisticated pathways contributes to CA initiation, progression, and rupture. This review aims to outline the complex mechanisms of EC dysfunction in CA pathogenesis.<\/jats:p>","DOI":"10.3171\/2019.4.focus19221","type":"journal-article","created":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T19:10:15Z","timestamp":1562353815000},"page":"E3","source":"Crossref","is-referenced-by-count":107,"title":["Endothelial dysfunction in cerebral aneurysms"],"prefix":"10.3171","volume":"47","author":[{"given":"Dallas L.","family":"Sheinberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Elwardany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Luther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie H.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Starke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3171\/jns.2005.102.1.0068","article-title":"Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size","volume":"102","author":"Akagawa H","year":"2005","unstructured":"Akagawa H, Kasuya H, Onda H, Yoneyama T, Sasahara A, Kim CJ, : Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size. 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