Menezes Junior Antonio da Silva, Nogueira Thallys Henrique Marques, de Lima Khissya Beatryz Alves, de Oliveira Henrique Lima, Botelho Silvia Marçal
Medicine School, Pontifical Catholic University of Goiás, Goiânia 74605-010, Brazil.
Faculty of Medicine, Internal Department, Federal University of Goiás, Goiânia 74001-970, Brazil.
J Pers Med. 2024 Dec 25;15(1):3. doi: 10.3390/jpm15010003.
Systemic arterial hypertension contributes to cardiovascular morbidity and mortality worldwide. Many patients cannot achieve optimal blood pressure (BP) control with traditional therapies, which often results in poor patient adherence and limited long-term efficacy. We investigated the potential of RNA interference (RNAi) therapies targeting hepatic angiotensinogen (AGT) for hypertension management. This scoping review was conducted by the Joanna Briggs Institute, following a six-stage methodological framework and adhering to PRISMA recommendations. A comprehensive search was conducted across seven databases to identify relevant studies published until May 2024. Data extraction was performed separately, and both quantitative and qualitative analyses were conducted. A population, concept, and context model-based search was performed, selecting controlled MeSH terms and uncontrolled descriptors and cross-referencing them using Booleans. Fifteen articles met our inclusion criteria. Focusing on the efficacy and safety of RNAi-based therapies, this review discusses several key approaches, including antisense oligonucleotides (IONIS-AGT-LRx), small interfering RNA (siRNAs; zilebesiran), and adeno-associated viruses carrying short hairpin RNAs. Notably, zilebesiran conjugated with N-acetylgalactosamine significantly reduced systolic BP by 20 mmHg, sustained for up to six months post-administration, with minimal adverse effects. RNAi-based therapies, particularly those using siRNAs, such as zilebesiran, are promising for the treatment of hypertension. They offer long-term BP control with fewer doses, potentially improving patient adherence and outcome. Although these therapies address several limitations of current antihypertensive treatments, further studies are required to confirm their long-term safety and efficacy.
全身性动脉高血压在全球范围内导致心血管疾病的发病和死亡。许多患者无法通过传统疗法实现最佳血压（BP）控制，这往往导致患者依从性差且长期疗效有限。我们研究了靶向肝脏血管紧张素原（AGT）的RNA干扰（RNAi）疗法在高血压管理中的潜力。本综述由乔安娜·布里格斯研究所进行，遵循六阶段方法框架并遵守PRISMA建议。在七个数据库中进行了全面搜索，以识别截至2024年5月发表的相关研究。分别进行了数据提取，并进行了定量和定性分析。进行了基于人群、概念和背景模型的搜索，选择了受控的医学主题词（MeSH）和非受控描述符，并使用布尔逻辑进行交叉引用。十五篇文章符合我们的纳入标准。本综述聚焦于基于RNAi疗法的疗效和安全性，讨论了几种关键方法，包括反义寡核苷酸（IONIS-AGT-LRx）、小干扰RNA（siRNAs；替乐贝生）以及携带短发夹RNA的腺相关病毒。值得注意的是，与N-乙酰半乳糖胺缀合的替乐贝生使收缩压显著降低了20 mmHg，给药后可持续长达六个月，且不良反应最小。基于RNAi的疗法，尤其是那些使用siRNAs的疗法，如替乐贝生，在高血压治疗方面具有前景。它们以较少的剂量提供长期血压控制，可能改善患者的依从性和治疗结果。尽管这些疗法解决了当前抗高血压治疗的一些局限性，但仍需要进一步研究来证实它们的长期安全性和疗效。
