Identification the main molecular mechanism of AT1R Non-desensitization

Abstract

Angiotensin II Type 1 Receptor Autoantibodies (AT1-AA) as a functional receptor activator can persistently activate Angiotensin II Type 1 Receptor (AT1R) by causing AT1R non-desensitization which is one of the important pathogenesis of preeclampsia (PE). However, the molecular mechanisms of AT1-AA results AT1R non-desensitization remain unknown. In order to explore the background molecular mechanisms of AT1R non-desensitization induced by AT1-AA, we construct dynamical models which are composed of control model (based on the body of healthy pregnant women) and experimental group models (based on the body of pregnant women with PE) in this paper. We also consider the effect of membrane fluidity on the reaction when building the dynamical models. In the experiment group models, we establish two models that caused AT1R non-desensitization: endocytosis disorder model and conformational change model. We write C++ and MATLAB programs to do the data fitting. By comparing the data fitting results and analyzing the images of models and corresponding Bayesian information criterion (BIC) values, we conclude that conformational changes may be the key molecular mechanism of AT1R non-desensitization.