Integrative Computational and experimental approach uncovering candidate biomarkers and therapeutic targets for coronary artery disease

Abstract

Coronary artery disease (CAD) is a complex disease that pathologically connects oxidative stress, inflammation, and metabolic changes, leading to a narrowing of blood vessels in the heart. Despite several studies, the incidence of CAD is increasing worldwide. Uncertainty in the predictive capabilities of biomarkers and in the selection of effective drug targets contributes to higher disease mortality. In this study, a systematic integrative computational and molecular approach was implemented to establish crucial biomarkers as well as drug targets for CAD. In addition, this study proposes potential drug candidates that could benefit the treatment of CAD. Our sequential investigation provides 9455 CAD-associated genes which regulate PI3K-Akt signalling, MAPK signalling, and Lipid metabolism that functionally linked with CAD pathogenesis. Particularly, Growth Factor Receptor Bound Protein 2 (GRB2) and Paraoxonase 1 (PON1) were overrepresented in our analysis. GRB2 is involved in signalling pathways related to cell growth and proliferation may contribute to the pathogenesis of CAD. Whereas PON1 is an antioxidant protein that functions as a protective factor against oxidative stress, inflammation, and metabolic changes that was downregulated in CAD patient samples. Additionally, assessments of CAD participants under CAD drug treatment showed a minimal effect on GRB2 but vigorously inhibited the beneficial anti-oxidant PON1, which suggests the need for alternate drugs to inhibit GRB2 and activate PON1. A virtual screen of the Piper betel photochemical against GRB2 and PON1 emphasized that the piperbetol compound has a potent inhibitory effect on GRB2, with a negligible effect on the beneficial PON1. Thus, our investigation suggests that PON1 and GRB2 could be the emerging biomarkers for CAD, and the utilization of Piper betel compounds holds potential therapeutic value for the condition. newline