Fulden Buyukozturk

Systemic Renin-Angiotensin-System

Fulden Buyukozturk on 10 Oct 2018 (Edited on 11 Jun 2020)
Latest activity Edit by Fulden Buyukozturk on 11 Jun 2020

This project presents SimBiology model implementation of the systemic Renin-Angiotensin-System that was first developed by Lo et al. and used to investigate the effects of different RAS-modulating therapies. The RAS pathway is crucial for blood pressure and kidney function control as well as a range of other organism-wide functions. The model describes the enzymatic conversion of the precursor protein Angiotensinogen to Angiotensin I and its downstream products Angiotensin 1-7, Angiotensin II and Angiotensin IV. Key pathway effects are triggered by the association of Angiotensin II with the AT1-Receptor. A positive feedback loop connects the Angiotensin II–AT1-Receptor complex with the Angiotensinogen conversion (not shown in the diagram). Enzymatic reactions are modeled as pseudo-unimolecular using enzymatic activities as reaction rates. Degradation reactions are described using protein half-life times. Drug pharmacodynamics are included in the model using the term (1-DrugEffect), where DrugEffect follows a sigmoidal dependence on the Drug concentration, to modify the target enzyme activity.

References [1] Lo, A., Beh, J., Leon, H. D., Hallow, M. K., Ramakrishna, R., Rodrigo, M., & Sarkar, A. (2011). Using a Systems Biology Approach to Explore Hypotheses Underlying Clinical Diversity of the Renin Angiotensin System and the Response to Antihypertensive Therapies. Clinical Trial Simulations, 1, 457–482.

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