Non-coding RNA-Associated Therapeutic Strategies in Atherosclerosis

Area of Science:

• Molecular Biology
• Cardiovascular Research
• RNA Therapeutics

Background:

• Atherosclerosis is a leading cause of global mortality and morbidity, characterized by chronic inflammation and plaque development in blood vessel walls.
• Key pathogenic mechanisms include immune cell accumulation, foam cell formation, and plaque rupture, leading to organ ischemia.
• Non-coding RNAs (ncRNAs) are increasingly recognized for their regulatory roles in cellular physiology and pathophysiology.

Purpose of the Study:

• To review recent advancements in understanding the role of ncRNAs in the pathophysiological processes of atherosclerosis.
• To explore the potential of ncRNAs as therapeutic targets for atherosclerosis.
• To discuss the development and clinical trials of RNA-based drugs for treating atherosclerosis.

Main Methods:

• Review of current scientific literature on ncRNAs and atherosclerosis.
• Analysis of studies investigating ncRNA involvement in cellular phenotypes relevant to atherosclerosis (e.g., endothelial dysfunction, foam cell formation).
• Examination of preclinical and clinical data on RNA-targeting drugs for atherosclerosis treatment.

Main Results:

• ncRNAs significantly influence key cellular processes in atherogenesis, including endothelial dysfunction, leukocyte recruitment, foam cell formation, and vascular smooth muscle cell apoptosis.
• ncRNAs demonstrate potential as biomarkers and therapeutic targets due to their regulatory functions in atherosclerotic development.
• RNA interference (RNAi) drugs, inspired by endogenous small interfering RNAs, show promise; inclisiran targeting PCSK9 mRNA exemplifies successful LDL-C reduction for atherosclerosis treatment.

Conclusions:

• ncRNAs are integral players in the complex pathogenesis of atherosclerosis.
• The unique regulatory roles of ncRNAs position them as promising targets for innovative therapeutic strategies.
• Ongoing research and clinical trials for RNA-based drugs offer new avenues for managing and treating atherosclerosis.