RGS proteins contribute to many complex polygenic human traits and pathologies such as hypertension, atherosclerosis, schizophrenia, depression, addiction, cancers, and many others.
Using rat models for spontaneous HTN (SHR) and experimentally-induced HTD we have observed that both cardiovascular risk factors lead to severe Pitx2 downregulation.
These include the contribution of variants of the regulator of G protein signaling (RGS) protein to hypertension; the role variants of the activator of G protein signaling (AGS) proteins to phenotypes (such as the type III AGS8 variant to hypoxia); the contribution of G protein-coupled receptor kinase (GRK) proteins, such as GRK4, in disorders such as hypertension.
Several RGS proteins have been implicated in the cardiac remodeling response and heart rate regulation, and changes in RGS protein expression and/or function are believed to participate in the pathophysiology of cardiac hypertrophy, failure and arrhythmias as well as hypertension.
Together, findings from the studies described herein suggest that development of methods to modulate the expression and function of RGS proteins may be a possible strategy for the treatment and prevention of hypertension and cardiovascular disease.
The study of the genomics of GPCR accessory proteins has also provided insight into pathways of disease, such as the contributions of regulator of G protein signaling (RGS) protein to hypertension and activator of G protein signaling (AGS) proteins to the response to hypoxia.