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Herein, we report a novel circular microfluidic stenosis model that recapitulates atherogenic flow-mediated endothelial dysfunction and blood-endothelial cell (EC) interactions\n                    <jats:italic>in vitro<\/jats:italic>\n                    . 2D and 3D stenosis microchannels with different constriction geometries were fabricated using 3D printing to study flow disturbances under varying severity of occlusion and wall shear stresses (100 to 2000 dynecm\n                    <jats:sup>\u22122<\/jats:sup>\n                    ). Experimental and fluid simulation results confirmed the presence of pathological shear stresses in the stenosis region, and recirculation flow post stenosis. The resultant pathological flow profile induced pro-inflammatory and pro-thrombotic EC state as demonstrated by orthogonal EC alignment, enhanced platelet adhesion at the stenosis, and aberrant leukocyte-EC interactions post stenosis. Clinical utility of the vascular model was further investigated by testing anti-thrombotic and immunomodulatory efficacy of aspirin and metformin, respectively. Overall, the platform enables multi-factorial analysis of critical atherogenic events including endothelial dysfunction, platelets and leukocyte adhesion, and can be further developed into a liquid biopsy tool for cardiovascular risk stratification.\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/aba501","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T18:30:50Z","timestamp":1594405850000},"page":"045009","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Recapitulating atherogenic flow disturbances and vascular inflammation in a perfusable 3D stenosis model"],"prefix":"10.1088","volume":"12","author":[{"given":"Nishanth Venugopal","family":"Menon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxun","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuin Tian","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhai Juan","family":"Phua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Min","family":"Tay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinkoo","family":"Dalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"King Ho Holden","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6631-6321","authenticated-orcid":false,"given":"Han Wei","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"bfaba501bib1","doi-asserted-by":"publisher","first-page":"e67-e492","DOI":"10.1161\/CIR.0000000000000558","type":"journal-article","article-title":"Heart disease and stroke statistics\u20142018 update: a report from the American Heart Association","volume":"137","author":"Benjamin","year":"2018","journal-title":"Circulation"},{"key":"bfaba501bib2","doi-asserted-by":"publisher","first-page":"327-387","DOI":"10.1152\/physrev.00047.2009","type":"journal-article","article-title":"Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives","volume":"91","author":"Chiu","year":"2011","journal-title":"Physiol. 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All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2020-02-27","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-07-10","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-07-28","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}