The Association of MicroRNA-21 with Carotid Artery Disease and Ischemic Stroke: From Pathophysiology to Clinical Implications and Potential Therapy

Abstract

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide, with carotid atherosclerosis being its key etiological factor. MicroRNA-21 (miR-21) regulates intracellular signal pathways responsible for vascular changes and ischemic brain injury, and is recognized as a potential diagnostic and prognostic biomarker. It modifies the activity of macrophages (MΦ) and vascular smooth muscle cells, causing inflammation and affecting the stability of atherosclerotic plaques. A deficiency of miR-21 in macrophages stimulates the inflammatory response and plaque growth. It promotes both the synthesis of extracellular matrix, stabilizing the plaque, and the degradation of the fibrin cap, which leads to plaque instability. The effect of miR-21 on endothelial cells differs: it stimulates both NO· synthesis and inflammation. During ischemic stroke, miR-21 demonstrates neuroprotective effects by modulating post-ischemic inflammation and protecting the integrity of the blood-brain barrier. Therapy targeting miR-21 shows potential in experimental models, but it requires cell-specific delivery and precise timing. Further research efforts should focus on the effects of miR-21 on different cell types, as well as the development of new technologies for diagnostic and therapeutic applications.

Keywords: asymptomatic carotid disease; atherosclerosis; biomarkers; cerebrovascular disease; endothelial dysfunction; ischemic stroke; therapeutic target; vascular inflammation.

Figure 1

Flowchart illustrating the literature selection process.

Figure 2

Schematic representation of miR-21–mediated signaling in macrophages (MΦ) and vascular smooth muscle cells during atherogenesis. Created with the BioRender online application, available at https://app.biorender.com/ (accessed 10 July 2025).

Figure 3

MiR-21–mediated neuroprotection in ischemic stroke. Upregulation of miR-21 after ischemic damage suppresses FASLG expression, reducing neuronal apoptosis and infarct volume. Created with the BioRender online application, available at https://app.biorender.com/ (accessed 10 July 2025).