Shenzhen Key Laboratory of Microbial Genetic Engineering, Vascular Disease Research Center, Department of Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.
Guangdong Provincial Key Laboratory of Regional Immunity and Disease, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.
Biomolecules. 2022 Mar 24;12(4):496. doi: 10.3390/biom12040496.
Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. Moreover, certain microRNAs, such as miR-150 and miR-26a, have been identified as good candidates of diagnosis biomarkers for PH. However, there are still several challenges for microRNAs as biomarkers, including difficulty in normalization, specificity in PH, and a lack of longitudinal and big sample-sized studies. Furthermore, microRNA target drugs are potential therapeutic agents for PH treatment, which have been demonstrated in PH models and in humans. Nonetheless, synthetic microRNA mimics or antagonists are susceptible to several common defects, such as low drug efficacy, inefficient drug delivery, potential toxicity and especially, off-target effects. Therefore, finding clinically safe and effective microRNA drugs remains a great challenge, and further breakthrough is urgently needed.
肺动脉高压（PH）是一种致命且无法治疗的疾病，最终会导致右心衰竭并最终导致死亡。microRNAs 是一种小型的、非编码的内源性 RNA 分子，可以调节基因表达并影响各种生物学过程。microRNA 表达水平的变化与各种心血管疾病有关，并且已经证明 microRNAs 在 PH 的发病机制中起着关键作用。近年来，许多研究都探讨了 microRNAs 在 PH 中的作用，重点关注了 microRNAs 的表达谱及其在肺动脉平滑肌细胞（PASMCs）或肺动脉内皮细胞（PAECs）、PH 模型和 PH 患者中的信号通路。此外，某些 microRNAs，如 miR-150 和 miR-26a，已被确定为 PH 诊断生物标志物的良好候选者。然而，microRNAs 作为生物标志物仍然存在几个挑战，包括难以标准化、在 PH 中的特异性以及缺乏纵向和大样本量的研究。此外，microRNA 靶向药物是 PH 治疗的潜在治疗剂，已在 PH 模型和人类中得到证实。尽管如此，合成的 microRNA 模拟物或拮抗剂容易出现几个常见的缺陷，如药效低、药物递送效率低、潜在毒性，尤其是脱靶效应。因此，寻找临床安全有效的 microRNA 药物仍然是一个巨大的挑战，迫切需要进一步的突破。
