The Effect of Endothelin-1 on Gene Expression of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase via Transforming Growth Factor Beta (TGF–β) Receptor in Human Aortic Smooth Muscle Cells

Background: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) is one of the predominant sources of the production of free oxygen radicals in the vascular wall. Endothelin-1 is a potent vasoconstrictor factor that also has mitogenic activity in vascular smooth muscle cells. The activation of transforming growth factor beta (TGF–β) receptor by endothelin-1 plays an important role in cardiovascular diseases. The aim of this study was to investigate the changes of Nox gene expression in smooth muscle cells treated with endothelin-1 in the presence of the transforming growth factor beta-receptor antagonist. Methods: Human aortic smooth muscle cells (HA-SMCs) were treated with endothelin-1 (100 nM) and transforming growth factor beta (2 ng/ml) in the presence and absence of transforming growth factor beta-receptor antagonist. The mRNA expression of Nox1 and Nox4 were assessed using real-time polymerase chain reaction (PCR) technique. Findings: The gene expression of Nox1 increased in the presence of endothelin-1 compared to control group, but there was no change in gene expression of Nox4. Increasing the expression of Nox1 decreased in the presence of transforming growth factor beta-receptor antagonist (10 μM). Conclusion: The results of this study showed that activation of transforming growth factor beta pathway is one of the mechanisms for increasing the mRNA expression of Nox1 by endothelin-1.