Innovative mRNA Vaccine Approaches in Targeting Atherosclerosis: A New Era in Cardiovascular Therapy.

Atherosclerosis, a major cause of cardiovascular disease (CVD), involves plaque buildup in arteries driven by inflammation, endothelial dysfunction, and lipid metabolism disturbances. Current therapies aim to reduce cholesterol through statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, prevent blood clots with antiplatelet drugs like aspirin, and control inflammation, alongside lifestyle modifications. However, these approaches often fall short due to patient non-compliance and residual risks. This review explores emerging mRNA vaccine strategies targeting the complex mechanisms of atherosclerosis. These vaccines could produce therapeutic proteins to modulate inflammation by encoding sequences that inhibit pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), stabilizing plaques. Key targets include interleukin-10 (IL-10) for plaque stability, PCSK9 for cholesterol regulation, and vascular endothelial growth factor (VEGF) for endothelial repair. Addressing these unmet needs, mRNA-based approaches offer the potential for more effective and personalized treatments for atherosclerosis. However, challenges remain, including difficulty replicating human atherosclerosis in preclinical models, regulatory concerns about long-term safety, and ensuring accessibility in low-resource settings. In addition, large and diverse clinical trials are needed to confirm the efficacy of these vaccines in reducing cardiovascular events.