Lack of association of restenosis with the T786C polymorphism of eNOS in atherosclerotic patients and in silico evidence of interaction between statin and the eNOS protein
Atherosclerosis is a multifactorial chronic-inflammatory disease related to endothelial aggression to the intima layer of medium and large caliber arteries. Hyperlipidemia and atherosclerosis cause eNOS to lose its function, producing superoxide and leading to endothelial dysfunction. The nitric oxide derived from eNOS is anti-atherogenic. Single nucleotide polymorphisms in the promoter region reduce its activity and predispose individuals to cardiovascular disease. We analyzed the T786C polymorphism of eNOS in atherosclerotic patients under statin treatment, to determine the clinical importance of this type of genetic variation. The study of this polymorphism in atherosclerotic patients with stents could help predict the probability of restenosis. We collected 79 peripheral blood samples from patients diagnosed with atherosclerosis undergoing statin treatment. These included 35 stent patients and 44 patients without stents. The TC genotype was prevalent in stent patients who smoke but there was no significant relation between the T786C polymorphism and restenosis. Based on an in silico approach through molecular modeling and molecular docking, we found that statins stabilize the eNOS protein. Seven amino acid residues in the eNOS binding pocket interact with the statin molecule; this family of drugs acts by stabilizing the eNOS protein. Thus, the use of such drugs may help reduce the risk of restenosis.