Association of metal elements deposition with symptomatic carotid artery stenosis and their spatial distribution in atherosclerosis plaques

Metals in circulation and urine had been implicated in atherosclerosis progression, but spatial distribution of metals within plaques and their association with plaque stability remained unclear. This study aimed to clarify differences of metal deposition between symptomatic and asymptomatic carotid plaques and metal spatial distribution within atherosclerotic plaques. We enrolled 15 asymptomatic and 53 symptomatic atherosclerotic plaque specimens during carotid endarterectomy. Each plaque was divided into the plaque core and thickened intimal area. We analyzed the difference of metals within plaques between symptomatic and asymptomatic groups and correlations between age and metal deposition. Besides, 12 additional symptomatic atherosclerotic plaques were used to map metal element distribution by laser ablation inductively coupled plasma mass spectrometry to analyze relative abundance of metal across pathological characteristics of plaques. Significantly higher levels of vanadium, iron, copper, molybdenum, and cadmium were found in the core area of symptomatic plaques compared to asymptomatic plaques, while no difference was observed in plaque thickened intimal area. Copper and lead deposition in core region of symptomatic plaques significantly increased with age. Spatial mapping indicated distinct metal distribution patterns: copper was primarily localized in necrotic and calcified regions, iron was in intraplaque hemorrhage, and calcium and zinc were in calcified areas. Elevated metal accumulation and distinct spatial distribution of metal elements within atherosclerotic plaques might contribute to plaque instability. Our findings highlighted the potential role of metal elements in plaque progression and value of spatial localization methods in studying the pathological roles of metal elements.