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To address this, we developed a 3-dimensional perfusable atherosclerotic vessel-on-a-chip (3D-PAVoC) platform that mimics vascular structure, blood circulating, and disease microenvironment. The system integrates endothelial cells and smooth muscle cells within a flow-enabled arterial construct, exposed to inflammatory (tumor necrosis factor-\u03b1 and interleukin-1\u03b2) and hyperlipidemic stimuli (oxidized low-density lipoprotein) to recreate AS-prone conditions. Flow-dependent endothelial responses including enhanced cell growth and survival were observed, confirming the importance of hemodynamics in disease modeling. Then, rapamycin (RAP) was used as a model drug to evaluate therapeutic effects in the 3D-PAVoC. Compared to static vessel-on-a-chip models and conventional 2-dimensional cultures, 3D-PAVoC exhibited more pronounced AS pathology and higher RAP half-maximal inhibitory concentration, better reflecting in\u00a0vivo conditions. The effective RAP dose identified in\u00a0vitro was validated in apolipoprotein E knockout (ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, where it partially alleviated AS progression. Transcriptomic analysis revealed RAP-mediated modulation of AS-related gene functions and pathways. Overall, the 3D-PAVoC provides a physiologically relevant platform for anti-AS drug screening, bridging the gap between in\u00a0vitro testing and in\u00a0vivo validation, and offering insights into drug action under realistic vascular and pathological conditions.\n                  <\/jats:p>","DOI":"10.34133\/research.0902","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T10:17:19Z","timestamp":1756808239000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":4,"title":["Microfluidic Perfusable Pathological Vasculature for Atherosclerosis Drug Screening"],"prefix":"10.34133","volume":"8","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong 523059, China."},{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulan","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong 523059, China."},{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Bai","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong 523059, China."},{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."},{"name":"GuangZhou Nanchuang Mount Everest Company for Medical Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentai","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong 523059, China."},{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9901-0927","authenticated-orcid":true,"given":"Zhilu","family":"Yang","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong 523059, China."},{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6749-3848","authenticated-orcid":true,"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong 523059, China."},{"name":"Shenzhen Clinical Medical School, \rSouthern Medical University, Guangzhou, Guangdong 510515, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"issue":"8","key":"e_1_3_4_2_2","first-page":"e93","article-title":"Heart disease and stroke statistics\u20142023 update: A report from the American Heart Association","volume":"147","author":"Tsao CW","year":"2023","unstructured":"Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Beaton AZ, Boehme AK, Buxton AE, et al. 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