siRNA-based therapeutics for lipoprotein (a) lowering: A path toward precision cardiovascular medicine.

IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Mehmet Kanbay, Lasin Ozbek, Mustafa Guldan, Zeynep Y Yilmaz, Alberto Ortiz, Francesca Mallamaci, Carmine Zoccali
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Abstract

Elevated Lp(a) is recognized as a significant independent risk factor for atherosclerotic cardiovascular diseases, including coronary artery disease, stroke and aortic valve stenosis. Notably, Lp(a) exhibits unique pro-inflammatory and pro-thrombotic properties contributing to its pathogenic role in cardiovascular disease. Although interventions targeting interleukin-6 (IL-6) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have been shown to reduce Lp(a) levels, the extent to which this reduction contributes to their overall cardiovascular benefits remains uncertain. Recent clinical trials have demonstrated that small interfering RNA (siRNA) therapies are effective in lowering Lp(a) levels, prompting ongoing investigations into their potential to improve cardiovascular outcomes. These developments highlight the clinical significance of targeting Lp(a) as a therapeutic strategy. This paper offers a comprehensive review of the pathophysiological role of Lp(a) as an independent cardiovascular risk factor, followed by an in-depth analysis of siRNA-based therapeutics designed to target Lp(a). It examines their mechanisms of action, clinical efficacy and safety profiles, while also addressing potential risks, limitations and challenges associated with Lp(a)-modulating siRNA treatments. Additionally, the review discusses other RNA-based therapeutic approaches for Lp(a) reduction, along with an overview of ongoing clinical trials. Finally, future perspectives are considered to assess the evolving therapeutic landscape and the potential advancements in Lp(a)-targeting strategies for improving cardiovascular outcomes.

基于sirna的脂蛋白(a)降低疗法:通往精准心血管医学之路。
Lp(a)升高被认为是动脉粥样硬化性心血管疾病的重要独立危险因素,包括冠状动脉疾病、中风和主动脉瓣狭窄。值得注意的是,Lp(a)表现出独特的促炎和促血栓特性,有助于其在心血管疾病中的致病作用。虽然针对白细胞介素-6 (IL-6)和枯草素/ keexin 9型蛋白转化酶(PCSK9)的干预措施已被证明可以降低Lp(a)水平,但这种降低对心血管总体益处的贡献程度仍不确定。最近的临床试验表明,小干扰RNA (siRNA)疗法在降低Lp(a)水平方面是有效的,这促使了对其改善心血管预后的潜力的持续研究。这些进展突出了靶向Lp(a)作为一种治疗策略的临床意义。本文全面回顾了Lp(a)作为独立心血管危险因素的病理生理作用,然后深入分析了基于sirna的靶向Lp(a)的治疗方法。它研究了它们的作用机制、临床疗效和安全性,同时也解决了与Lp(a)调节siRNA治疗相关的潜在风险、局限性和挑战。此外,本文还讨论了其他基于rna的Lp(a)降低治疗方法,并概述了正在进行的临床试验。最后,考虑未来的观点来评估不断发展的治疗前景和Lp(a)靶向策略改善心血管预后的潜在进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.50
自引率
3.60%
发文量
192
审稿时长
1 months
期刊介绍: EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.
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