Feasibility of Endothelial Cell Isolation from Routine Coronary Function Testing in ANOCA Patients

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Abstract
Background: Angina with nonobstructive coronary arteries (ANOCA) is a heterogeneous condition encompassing distinct endotypes representing different underlying pathophysiological mechanisms. Endothelial dysfunction is considered a central hallmark of ANOCA. However, studying patient-derived endothelial cells (ECs) remains challenging due to the limited availability of disease-specific endothelial samples. We therefore aimed to assess the feasibility of isolating and culturing ECs from catheterization material obtained during routine coronary function testing in ANOCA patients. Methods: Catheterization material was collected from 79 ANOCA patients (84% female, age 58±10 years) undergoing coronary function testing. ECs were isolated, expanded and characterized using immunostaining, flow cytometry, gene expression profiling and functional assays. Results: EC isolation was successful in 43% of cases and resulted in 34 primary EC cultures that were expanded up to passage 10. Isolation success was independent of clinical or procedural characteristics. Isolated cells exhibited typical EC morphology and expressed EC markers confirmed by immunostaining, flow cytometry and gene expression analyses. EC marker gene expression remained largely stable over passages. However, stress- and defense-related gene expression programs increased over time, while proliferation-related processes decreased. Functional assays demonstrated that the coronary catheterization-derived ECs showed typical properties of wound healing, angiogenesis, activation responses upon stimuli and monocyte adhesion. Conclusions: This study demonstrates the feasibility of isolating and expanding ECs directly from catheterization material collected during routine coronary function testing in ANOCA patients. These patient-derived ECs retain characteristic endothelial features and functionality. This approach offers primary EC cultures to study the mechanisms underlying endothelial dysfunction in ANOCA. Graphic Perspectives: Clinical perspective: What is new?: We established a method to isolate and culture endothelial cells from routine coronary catheterization material in patients with ANOCA, enabling direct study of patient-specific endothelial dysfunction. The patient-derived endothelial cells exhibit characteristic morphology, express canonical endothelial markers and retain functional properties consistent with endothelial physiology. What are the clinical implications?: This approach provides a clinically relevant platform to investigate mechanisms underlying ANOCA and may support the development of personalized diagnostic and therapeutic strategies. Broader application of this method could facilitate translational research in other vascular pathologies where access to endothelial tissue is limited.

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