Universiteit Leiden

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Proefschrift

Metabolomics study of blood vessels-on-chip model

Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

Auteur
K. Kallakkudi Pandian
Datum
26 maart 2025
Links
Thesis in Leiden Repository

Although research has advanced, traditional in vitro models often lack essential features such as blood flow, cell interactions, and a proper extracellular matrix, while animal models frequently fail to mimic human conditions. Microfabricated "vessels-on-a-chip" address these gaps by combining blood vessel physiology, transport phenomena, cell biology, and tissue microfabrication to accurately recreate endothelial cells, 3D ECM, and microcirculation structures under controlled conditions. These advanced models are especially valuable for studying vasodilatory compounds like nitric oxide (NO), whose direct measurement is challenging due to its short half-life. Metabolomics offers an alternative by profiling NO metabolites. Thus, this thesis aims to develop a mass spectrometry method for analyzing NO-related metabolites using a physiologically relevant 3D microvessel-on-chip model to investigate disease conditions, the effects of hypoxia on blood vessels, and advanced techniques for single-cell metabolite analysis.

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