Date of Award

Spring 2026

Document Type

Open Access Thesis

Department

Biomedical Science

First Advisor

Wenbin Tan

Abstract

Port-wine stains (PWS), clinically classified as capillary malformations (CM), are congenital vascular anomalies characterized by abnormally dilated dermal capillaries that persist throughout life and may progressively darken and thicken with age. Pulsed dye laser (PDL) therapy remains the clinical standard of care for PWS; however, complete lesion clearance is uncommon and many patients experience incomplete or temporary responses. Increasing evidence suggests that endothelial survival and vascular remodeling following laser exposure may contribute to lesion persistence and recurrence, highlighting the need for adjunct therapeutic strategies that target the underlying cellular mechanisms of vascular recovery. This thesis investigates endothelial dysfunction and therapeutic targeting in capillary malformations through a combination of foundational vascular modeling studies, mechanistic literature synthesis, and exploration of pharmacological adjunct approaches. Foundational research summarized in this work includes the development of patient-derived vascular organoid models and molecular characterization of CM vasculature, which revealed disease-relevant endothelial phenotypes and signaling pathways associated with vascular remodeling. These findings provide insight into the biological processes that may limit the effectiveness of laser therapy alone. Building on this framework, the thesis evaluates the therapeutic potential of xanthohumol (XN), a prenylated chalcone derived from hops (Humulus lupulus) with reported anti-inflammatory, anti-angiogenic, and endothelial-modulating properties. A comprehensive review of XN’s molecular mechanisms and biological activities is presented to establish its relevance to vascular and endothelial biology. Together, these studies provide a conceptual and experimental foundation for investigating XN as a potential adjunct to laser therapy in endothelial models of capillary malformations. Collectively, this work advances the understanding of endothelial mechanisms underlying capillary malformations and highlights the potential of combination therapeutic strategies that integrate pharmacological targeting with existing laser-based treatments.

Rights

© 2026, Mackenzie Azuero

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