The Use of microRNAs for the Treatment of Atherosclerosis: Current Status

Abstract

: Atherosclerosis remains the principal substrate of ischaemic heart disease and stroke, and residual cardiovascular risk persists despite intensive lipid-lowering and anti-inflammatory therapy. microRNAs (miRNAs) act as integrative regulators of endothelial activation, macrophage polarisation, foam cell formation, smooth muscle cell phenotypic switching, and plaque stability, offering network-level modulation that single-target drugs cannot achieve. This review summarises the current status of miRNA-based approaches to atherosclerosis. We outline miRNA biogenesis, survey the miRNAs with the strongest causal evidence in atherogenesis (miR-33, miR-92a, miR-126, miR-146a, miR-155, miR-21, miR-181b, miR-143/145, miR-223, miR-712/205, and the miR-17~92 cluster), and describe the principal therapeutic modalities and delivery platforms. We review clinical experience with miRNA-directed agents in other indications, the only direct human safety data currently available, and analyse the obstacles that have prevented any miRNA therapeutic from reaching late-stage atherosclerosis trials: pleiotropy, tissue-restricted delivery, immunogenicity, species differences, and the absence of validated pharmacodynamic biomarkers. Finally, we consider how targeted delivery, combination therapy, and miRNA-based patient stratification might convert this literature into a viable therapeutic class.