Mehmet Kanbay, Lasin Ozbek, Mustafa Guldan, Zeynep Y Yilmaz, Alberto Ortiz, Francesca Mallamaci, Carmine Zoccali
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引用次数: 0
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.
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.