In Silico Modulation of the Interaction Between VEGF and eNOS Proteins in Atherosclerosis as a Future Diagnostic and Therapeutic Approach

Atherosclerosis is related to other cardiovascular diseases such as angina, infarction, hypertension and cardiac death. Several risk factors influence atherosclerosis onset and progression, the main ones are diabetes, sedentary lifestyle, high blood pressure, obesity, alcohol consumption, smoking and cholesterol. Atherosclerosis is a globally serious health problem, affecting over millions of people worldwide. Endothelial dysfunction and angiogenesis may be associated with genetic polymorphisms that take place in genes and proteins with essential roles in maintaining endothelial and cardiovascular homeostasis. Among these genes, eNOS and VEGF stand out, being responsible for the synthesis of nitric oxide and angiogenesis, respectively. Dysfunction affecting any of those proteins, their structures or the protein interaction patterns they establish may increase atherosclerosis and other diseases susceptibility. Here, we perform an in silico analysis of the interaction interfaces between angiogenesis-related protein VEGF and the nitric oxide production protein eNOS. VEGF and eNOS influence the onset of atherosclerosis and they present polymorphisms that could increase the susceptibility to cardiovascular diseases such atherosclerosis. We identified important hot spots within the interaction interface of VEGF and eNOS. We also compared hot spot residues with clinical significant polymorphisms of those proteins regarding the onset and progression of atherosclerosis. Finally, we designed peptides that could modulate the interaction of VEGF and eNOS as a perspective of future treatment and better prognostic for atherosclerotic patients.