剪应力
体内
血管生成
生物
腹主动脉瘤
病理
基因
动脉
癌症研究
医学
生物医学工程
心脏病学
动脉瘤
放射科
材料科学
生物技术
复合材料
生物化学
作者
Valentina Paloschi,Jessica Pauli,Greg Winski,Zhiyuan Wu,Zhaolong Li,Lorenzo Alessio Botti,Sandro Meucci,Pierangelo Conti,Felix Rogowitz,Nadiya Glukha,Nora Hummel,Albert Busch,Ekaterina Chernogubova,Hong Jin,Nadja Sachs,Hans‐Henning Eckstein,Anne Dueck,Reinier A. Boon,Andreas R. Bausch,Lars Maegdefessel
标识
DOI:10.1002/adhm.202302907
摘要
Abstract In this study, organ‐on‐chip technology is used to develop an in vitro model of medium‐to‐large size arteries, the artery‐on‐a‐chip (AoC), with the objective to recapitulate the structure of the arterial wall and the relevant hemodynamic forces affecting luminal cells. AoCs exposed either to in vivo‐like shear stress values or kept in static conditions are assessed to generate a panel of novel genes modulated by shear stress. Considering the crucial role played by shear stress alterations in carotid arteries affected by atherosclerosis (CAD) and abdominal aortic aneurysms (AAA) disease development/progression, a patient cohort of hemodynamically relevant specimens is utilized, consisting of diseased and non‐diseased (internal control) vessel regions from the same patient. Genes activated by shear stress follow the same expression pattern in non‐diseased segments of human vessels. Single cell RNA sequencing (scRNA‐seq) enables to discriminate the unique cell subpopulations between non‐diseased and diseased vessel portions, revealing an enrichment of flow activated genes in structural cells originating from non‐diseased specimens. Furthermore, the AoC served as a platform for drug‐testing. It reproduced the effects of a therapeutic agent (lenvatinib) previously used in preclinical AAA studies, therefore extending the understanding of its therapeutic effect through a multicellular structure.
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