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

Keck, S. A.; Mullen, N.; Taylor, A. E.; Gliligan, L. C.; Pyle, M.; Shrestha, T. B.; Sebek, J.; Highland, M. A.; Challapalli, R.; Arlt, W.; Bossmann, S. H.; Dennedy, M. C.; Prakash, P.; Basel, M. T.

doi:10.1101/2024.05.07.592955

bioRxiv · 10.1101/2024.05.07.592955

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

Keck, S. A.·Mullen, N.·Taylor, A. E.·Gliligan, L. C.·Pyle, M.·Shrestha, T. B.·Sebek, J.·Highland, M. A.·Challapalli, R.·Arlt, W.·Bossmann, S. H.·Dennedy, M. C.·Prakash, P.·Basel, M. T.

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Abstract

IntroductionAldosterone-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, MethodsA 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. ResultsThe 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. ConclusionThe HAC15 model is a useful tumor model to study and develop localized treatment methods for APA.

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Keck, S. A., Mullen, N., Taylor, A. E., Gliligan, L. C., Pyle, M., Shrestha, T. B., Sebek, J., Highland, M. A., Challapalli, R., Arlt, W., Bossmann, S. H., Dennedy, M. C., Prakash, P., Basel, M. T.. 2024-05-10. Characterization of a Biochemical Mouse Model of Primary Aldosteronism for Thermal Therapies. https://doi.org/10.1101/2024.05.07.592955

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