miR-1226-3p Promotes eNOS Expression of Pulmonary Arterial Endothelial Cells to Mitigate Hypertension in Rats via Targeting Profilin-1

Abstract

In pulmonary arterial hypertension (PAH), microRNAs (miRNAs) are related with dysfunction of pulmonary arterial endothelial cells. miR-1226-3p was found to be downregulated in the serum of PAH patients, while few studies have illustrated the regulation mechanism of miR-1226-3p on PAH. In this study, we aimed to systematically investigate the role of miR-1226-3p in PAH. Sprague-Dawley (SD) rats were treated with monocrotaline (MCT) to establish the PAH models. The right ventricular systolic pressure (RVSP), ratio of the right ventricle to the left ventricle with septum (RV/(LV+S) ratio), and nitric oxide (NO) content were used to reflect the symptom of the rats. The rat models were used to observe the regulation mechanism of miR-1226-3p on PAH, and dual-luciferase reporter assay was used to verify the binding effect of miR-1226-3p to Pfn1. Besides, the qRT-PCR and western blot were used to measure the expression levels of miR-1226-3p and some keys proteins such as eNOS and Pfn1, respectively. The results showed that the PAH models were established successfully. The RVSP levels and the RV/(LV+S) ratio of the PAH rats were higher than those indexes in normal rats, while the NO content showed the opposite trends. Besides, the decreased miR-1226-3p and eNOS were, respectively, found in the PAH rats and rPAECs, and overexpressed miR-1226-3p could reverse the disadvantages of the PAH rats including increased RVSP, high RV/(LV+S) ratio, and decreased NO content. Furthermore, miR-1226-3p could directly target the 3 ${}^{\prime }$ -UTR of Profilin-1 (Pfn1). Overexpressed Pfn1 led to decreased eNOS, while miR-1226-3p could partly inhibit the expression of Pfn1 and increase the expression level of eNOS in rPAECs. In summary, this study suggests miR-1226-3p as a protector to increase eNOS, improve NO content in rPAECs of the PAH rats via targeting Pfn, and finally protect the rats from the injury induced by PAH.