Polyethylene and polyvinyl chloride nanoparticles—the most common plastics found in human arterial plaques—accelerate atherosclerosis in mice through polymer-specific mechanisms. Polyethylene drives smooth muscle cells toward a bone-like state with increased vascular calcification, while PVC promotes a fiber-producing program that enhances cell migration without calcification. Both pathways reduce contractile function in arterial walls. The research used single-cell sequencing to map these distinct cellular transformations and found matching patterns in human carotid artery plaques from symptomatic patients. This represents the first causal evidence linking specific plastic polymers to accelerated heart disease through defined molecular pathways. The findings are particularly concerning given the ubiquity of these materials in food packaging, water bottles, and medical devices. However, several limitations apply: this mouse study used oral dosing that may not reflect typical human exposure levels or routes, and the cardiovascular outcomes in genetically modified atherosclerosis-prone mice may not translate directly to humans. As a preprint awaiting peer review, these results require validation before informing clinical practice, though they provide an important mechanistic framework for understanding plastic pollution's cardiovascular risks.