Therapeutic Design of Peptide Modulators of the Interaction Between eNOS and p53 in Atherosclerosis

Abstract

Atherosclerosis is a cardiovascular disease featuring a chronic inflammation due to the accumulation of lipids within the tunica intima of arteries. The development of the disease depends on dynamic changes in the vascular biology. Immune system cells directly influence the pathogenesis of atherosclerosis during the inflammatory process. Currently, atherosclerosis diagnosis is performed by non-invasive or invasive methods depending on the type of arteries that are being investigated. New diagnostic and therapeutic procedures should improve the quality of life of patients. Some of the genes that could be biomarkers of cardiovascular diseases are TP53 and eNOS. The protein p53 is recognized as a tumor suppressor protein that controls DNA repair, cell cycle progression or arrest and apoptosis. These functions that p53 exerts are well known and some other functions are being investigated, such as its role in the cardiovascular system. The eNOS gene regulates the levels of nitric oxide, which is vital for several intracellular biological functions, such as vasodilation, vascular homeostasis, protection of arteries against injuries, cellular growth, signaling pathways and immune response among others. Here, we used an in-silico approach to predict four models of interaction between clinically important proteins (eNOS and p53), to predict the interface of interaction and to rationally design modulating peptides to be tested in vitro and in vivo and possibly used as a therapeutic agent.