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Researchers developed an in vitro model of intracranial aneurysms using endothelialized vessel constructs subjected to cardiovascular flow conditions for up to five days to study cellular responses to hemodynamic stress. They found that flow initiation triggered a transient inflammatory response with elevated MCP-1 and TNF-α at day two, which resolved by day five despite continued hemodynamic loading, and that cardiovascular flow patterns provided greater endothelial stability compared to steady flow. The study identified specific cytokine release signatures that may serve as biomarkers for aneurysm remodeling and demonstrated the importance of long-term perfusion and physiologically relevant flow waveforms in modeling vascular disease.
Why it matters
This work could improve prediction of intracranial aneurysm rupture risk by identifying cytokine biomarkers that reflect underlying vessel remodeling processes. The in vitro platform enables more physiologically relevant testing of aneurysm progression mechanisms and potential therapeutic interventions under controlled conditions that better mimic cardiovascular flow.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Intracranial aneurysm (IA) rupture is catastrophic, yet current models of rupture-risk inadequately capture underlying IA remodelling mechanisms. Endothelial-haemodynamic interactions are central to these processes, but in vitro flow platforms often lack vessel relevant geometry or long-term perfusion. Here, temporal and spatial endothelial responses to haemodynamic stress were investigated across idealised and patient-specific vascular models. Polydimethylsiloxane models were endothelialised with human aortic endothelial cells then perfused at up to 1.6 Pa wall shear stress for five days. IA models were exposed to steady or cardiovascular flow waveforms, with endothelial phenotype assessed by immunofluorescence and cytokine profiling. Flow initiation induced a transient inflammatory response, with elevated MCP-1 and TNF- at day two, followed by a resolution of cytokine levels by day five, including a ~7.5-fold reduction in MCP-1, despite increased haemodynamic loading. Endothelial cells retained a cobblestone-like morphology with eNOS undetected, resembling a partially activated phenotype. Compared with steady flow, cardiovascular flow reduced TGF {beta}1 and IL-8 secretion and decreased FGF-b consumption (~2.5 fold), suggesting enhanced phenotypic stability. This study presents the first in vitro IA model incorporating a cardiovascular flow waveform and identifies cytokine signatures with potential utility as biomarkers of IA remodelling, highlighting the importance of long-term perfusion for modelling chronic vascular disease.