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[Preprint]. 2024 May 10:2024.05.07.592955. [Version 1] doi: 10.1101/2024.05.07.592955

Characterization of a Biochemical Mouse Model of Primary Aldosteronism for Thermal Therapies

Sarah A Timmerman, Nathan Mullen, Angela E Taylor, Lorna C Gilligan, Marla Pyle, Tej B Shrestha, Jan Sebek, Margaret A Highland, Ritihaas Challapalli, Wiebke Arlt, Stefan H Bossmann, Michael Conall Dennedy, Punit Prakash, Matthew T Basel
PMCID: PMC11100708  PMID: 38766205

Abstract

Introduction

Aldosterone-producing adenoma (APA) is the most common cause of endocrine-related hypertension but surgery is not always feasible. Current medical interventions are associated with significant side effects and poor patient compliance. New APA animal models that replicate basic characteristics of APA and give physical and biochemical feedback are needed to test new non-surgical treatment methods, such as image-guided thermal ablation,

Methods

A model of APA was developed in nude mice using HAC15 cells, a human adrenal carcinoma cell line. Tumor growth, aldosterone production, and sensitivity to angiotensin II were characterized in the model. The utility of the model was validated via treatment with microwave ablation and characterization of the resulting physical and biochemical changes in the tumor.

Results

The APA model showed rapid and relatively homogeneous growth. The tumors produced aldosterone and steroid precursors in response to angiotensin II challenge, and plasma aldosterone levels were significantly higher in tumor bearing mice two hours after challenge verses non-tumor bearing mice. The model was useful for testing microwave ablation therapy, reducing aldosterone production by 80% in treated mice.

Conclusion

The HAC15 model is a useful tumor model to study and develop localized treatment methods for APA.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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