The Role of EDN-1 and iNOS genes expression in Cardiovascular Diseases

Abstract

One of the key regulators that contributes to several pathologies, including cardiovascular diseases, is the peptide known as endothelin-1 (ET-1), along with nitric oxide (NO); both of these molecules orchestrate the vasoconstriction and vasodilation of blood vessels, which play a pivotal role in CVD.In this regard, many research laboratories have studied the functions of endothelin-1 and nitric oxide in relation to CVD. The aim of this study was to investigate the role of endothelin-1 and nitric oxide in CVD patients at the gene expression levels. A case-control research was performed in Kirkuk Governorate from December 2024 to April 2025, with 75 participants aged 50 to 80 years, comprising 50 patients with cardiovascular disease under the supervision of a specialist physician for treatment and clinical monitoring. A control group including 25 persons devoid of cardiac disease was established. The result of the present study investigating endothelin-1 protein concentrations was markedly lower in cardiovascular disease patients than in healthy controls. The mean Endothelin-1 level was (356.63 ± 106.89, 452.07± 86.53 pg/mL, respectively, at a p-value ≤ 0.001. Nitric oxide protein concentrations were markedly higher in cardiovascular-disease patients than in healthy controls. The mean nitric oxide level was (110.39 ± 43.89, 86.40 ± 27.78) pg/mL, at a p-value ≤ 0.001. Gene expression analysis revealed significant differences between the CVD patient group and the control group. EDN1 gene expression was significantly lower in the patients compared to the control group, with a mean normal expression of 0.070 versus 1.00 in the control group, representing a 14.25-fold decrease. In contrast, iNOS gene expression was significantly higher in the CVD patients, with a mean expression of 2.287 compared to the control reference value (1.00), representing a 2.29-fold increase. The present study demonstrated endothelin-1 highly decreased protein levels, while NO was shown to be overexpressed in cardiovascular disease. In contrast, downregulation of EDN-1 gene expression and upregulation of iNOS gene expression are indicative of promising approaches in CVD applications and clinical trials.