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Herein, we established a modified \u201cH\u00e4utchen method\u201d for the local isolation of endothelial cells (ECs) from mouse aorta to analyze their spatial heterogeneity and potential role in site-specific disease development. When we compared ECs from aneurysm predilection sites of healthy mice with adjacent control segments we found regulation of genes related to extracellular matrix remodeling, angiogenesis and inflammation, all pathways playing a critical role in aneurysm development. We also detected enhanced cortical stiffness of the endothelium at these sites. Gene expression of ECs from aneurysms of the AngII\u00a0ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> model when compared to sham animals mimicked expression patterns from predilection sites of healthy animals. Thus, this work highlights a striking genetic and functional regional heterogeneity in aortic ECs of healthy mice, which defines the location of aortic aneurysm formation in disease.<\/jats:p>","DOI":"10.1007\/s10456-024-09933-9","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T16:01:58Z","timestamp":1720108918000},"page":"719-738","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Site-specific genetic and functional signatures of aortic endothelial cells at aneurysm predilection sites in healthy and AngII\u00a0ApoE\u2212\/\u2212 mice"],"prefix":"10.1007","volume":"27","author":[{"given":"Alexander","family":"Br\u00fcckner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Brandtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Rieck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Matthey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Geisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Fels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Stei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kusche-Vihrog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd K.","family":"Fleischmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"issue":"6","key":"9933_CR1","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1161\/01.CIR.0000154569.08857.7A","volume":"111","author":"EM Isselbacher","year":"2005","unstructured":"Isselbacher EM (2005) Thoracic and abdominal aortic aneurysms. 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