Spatiotemporally Mapped Endothelial Dysfunction at Bifurcations in a Coronary Artery‐on‐a‐Chip

Endothelial Dysfunction
DOI: 10.1002/admt.202301596 Publication Date: 2024-03-03T21:10:31Z
ABSTRACT
Abstract Atherosclerotic plaques are commonly observed at low shear regions, in particular, the left main coronary artery (LMCA) bifurcation. Low regions bifurcations promote endothelial dysfunction, a key factor initiating atherogenesis, however, mechanisms underlying this process poorly understood. Dynamic vitro models critical to investigate but current static and vessels‐on‐chip systems typically lack physiologically complex geometries local changes. Here, bifurcating artery‐on‐a‐chip is developed, mimicking human LMCA, displaying reduced near bifurcation, verified using computational fluid dynamics simulations. Over 7 days of dynamic culture, cells aligned with flow expressed more Endothelial nitric oxide synthase (eNOS) intercellular cell adheison molecule‐1 (ICAM‐1) high (12.7 dyn cm −2 ) adjacent to, not bifurcation (0–3 ). After tumor necrosis factor‐alpha (TNFα) stimulation induce spatially mapping cellular changes gradients revealed alignment disrupted over larger area surrounding higher shear, ICAM‐1 expression increased closer lower shear. This establishes system map behavior response differential vessel geometry, enabling future studies into plaque initiation events, treatment targets, drug screening.
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