Rajabi Soodeh, Najafipour Hamid, Sheikholeslami Mozhgan, Jafarinejad-Farsangi Saeideh, Beik Ahmad, Askaripour Majid, Karam Zahra Miri
Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Science, Kerman, Iran.
Noncoding RNA Res. 2022 Jan 28;7(1):27-33. doi: 10.1016/j.ncrna.2022.01.005. eCollection 2022 Mar.
Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play critical roles in the pathogenesis and progression of pulmonary artery hypertension (PAH). LncRNA H19, myocardial infarction-associated transcript (MIAT), miR-29a, and miR-33a have been suggested as potential targets for treating arterial hypertension. We explored the expression pattern of non-coding RNAs H19, MIAT, miR-29a, and miR-33a in monocrotaline (MCT)-induced PAH rats. Moreover, we investigated whether perillyl alcohol (PA) and quercetin (QS), two plant derivatives with beneficial effects on PAH-induced abnormalities, act through regulating the expression of these non-coding RNAs.
Male Wistar rats ( = 30) were divided into five groups. MCT (60 mg/kg) was injected subcutaneously to induce PAH. PA (50 mg/kg daily) and QS (30 mg/kg daily) were administered three weeks after induction of PAH. H&E staining and qRT-PCR were performed to assess arteriole wall thickness and gene expression, respectively.
Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) increased in MCT and MCT + Veh. groups compared to the control group (in both < 0.001). QS and PA decreased RVSP and RVH significantly. Wall thickness and fibrosis score in the MCT group (score 3) increased compared to the control group (score 0). PA and QS ameliorated wall thickness and fibrosis to score 1 (mild). Also, the expression of miR-29a and miR-33a decreased in the PAH group (in both, < 0.001). Treatment with PA and QS decreased the expression of H19 ( < 0.001) and MIAT ( < 0.01) and increased the expression of miR-29a ( < 0.01) and miR-33a significantly ( < 0.05 for QS and < 0.001 for PA).
The beneficial effects of PA and QS on PAH-induced abnormalities were exerted through returning the dysregulated expression of H19, MIAT, miR-29a, and miR-33a to normal levels in rats with MTC-induced PAH. This study emphasized the therapeutic potential of PA and QS in PAH. However, more detailed investigations are needed to clarify the underlying molecular mechanisms.
非编码RNA，包括长链非编码RNA（lncRNA）和微小RNA（miRNA），在肺动脉高压（PAH）的发病机制和进展中起关键作用。LncRNA H19、心肌梗死相关转录本（MIAT）、miR-29a和miR-33a已被认为是治疗动脉高血压的潜在靶点。我们探讨了非编码RNA H19、MIAT、miR-29a和miR-33a在野百合碱（MCT）诱导的PAH大鼠中的表达模式。此外，我们研究了对PAH诱导的异常具有有益作用的两种植物衍生物紫苏醇（PA）和槲皮素（QS）是否通过调节这些非编码RNA的表达发挥作用。
将30只雄性Wistar大鼠分为五组。皮下注射MCT（60mg/kg）诱导PAH。PAH诱导三周后给予PA（每日50mg/kg）和QS（每日30mg/kg）。分别进行苏木精-伊红（H&E）染色和定量逆转录聚合酶链反应（qRT-PCR）以评估小动脉壁厚度和基因表达。
与对照组相比，MCT组和MCT+Veh组的右心室收缩压（RVSP）和右心室肥厚（RVH）增加（两者均P<0.001）。QS和PA显著降低了RVSP和RVH。与对照组（评分0）相比，MCT组的壁厚度和纤维化评分增加（评分3）。PA和QS将壁厚度和纤维化改善至评分1（轻度）。此外，PAH组中miR-29a和miR-33a的表达降低（两者均P<0.001）。PA和QS治疗降低了H19（P<0.001）和MIAT（P<0.01）的表达，并显著增加了miR-29a（P<0.01）和miR-33a的表达（QS为P<0.05，PA为P<0.001）。
PA和QS对PAH诱导的异常的有益作用是通过将MTC诱导的PAH大鼠中H19、MIAT、miR-29a和miR-33a失调的表达恢复到正常水平来实现的。本研究强调了PA和QS在PAH中的治疗潜力。然而，需要更详细的研究来阐明潜在的分子机制。
