Investigation into cardiovascular effects of Regulator of Gprotein signaling2 RGS2 agonist in animal models of cardiovascular complications

Abstract

Now a day, cardiovascular diseases (CVDs) are most one of the leading cause of worldwide mortality and morbidity. According to WHO, it was estimated that 17.9 million people died from CVDs in 2016 which representing 31% of all the global deaths. The underlying pathogenesis of cardiovascular diseases suggested the hyperactivity of various stimulatory mediators such as endothelin-1 (ET-1), angiotensin II, adrenaline and noradrenaline as major contributing factors. However, these mediators produce their action via G-protein coupled receptors (GPCRs). GPCRs are one of the largest subfamily of cell surface receptors and largest class of drug target. More than 100 GPCRs are expressed in cardiovascular system and regulate the essential cardiovascular functions. Thus, abnormalities in the GPCR signaling has crucial role in the development of cardiovascular complications. The previous reports suggested that chronic hyper-activation of GPCR signaling, especially Gand#945;q signaling leads to development of various cardiovascular abnormalities such as cardiac hypertrophy, fibrosis, and heart failure. The GPCR signaling is controlled at receptor levels by agonist and antagonist drugs as well as at intracellular signaling components. Regulator of G-protein signaling (RGS) proteins are major contributor to regulate the GPCRs functioning at the intracellular signaling components. RGS proteins are negative regulator of GPCR signaling. Numerous of evidences ranging from biochemical characterizations to genetic studies demonstrated the RGS proteins as potential drug target in cardiovascular diseases. Therefore, we have aimed to identify the binding affinity of small molecule (Gand#945;q signaling inhibitor) on RGS2, RGS4 and RGS5, establish toxicity profile and therapeutic potential with possible mechanisms in cardiovascular diseases. newline newline