Atherosclerotic plaques in humans are primarily composed of smooth muscle cells. This study investigates whether these plaques are monoclonal or polyclonal in origin. Using X-linked glucose-6-phosphate dehydrogenase (G6PD) in heterozygous females, researchers analyzed 30 plaques and 59 samples from four females. The results showed that fibrous caps of atheromatous plaques, even large ones, consist of cells producing a single enzyme type, while normal artery wall tissues contain a mixture of cell types. This suggests that atherosclerotic plaques are monoclonal, not a response to injury or healing. The monoclonal nature is likely due to mutations, possibly caused by chemical mutagens or viruses. Atherosclerosis is a progressive disease of major arteries, characterized by fibrous plaques composed mainly of smooth muscle cells surrounded by collagen. The study compared human and avian atherosclerotic plaques with responses to injury in mammalian aortas, leading to the hypothesis that atherosclerotic plaques arise from a different mechanism than injury repair. Cells in atherosclerotic plaques differ from normal artery wall cells in size, extracellular material composition, and lack of intercellular junctions, suggesting they may originate from a different cell population or be transformed cells. The study used G6PD isoenzymes to analyze enzyme patterns in plaques and normal tissues. Results showed that individual plaques had consistent enzyme patterns, indicating monoclonal origin. Analysis of 81 samples from 30 plaques and 59 normal tissues revealed that some plaques were predominantly of one enzyme type, while others were mixed. The data suggest that atherosclerotic plaques are monoclonal, possibly due to mutations. The study also found that the appearance of a monoclonal enzyme pattern in some normal artery wall samples may indicate early plaque formation. The study concludes that atherosclerotic plaques are monoclonal, likely due to mutations, and that factors such as chemical mutagens or viruses may be involved. The findings challenge the traditional injury-repair hypothesis and suggest that atherosclerosis may result from cell transformation rather than injury. The study highlights the importance of considering cell transformation in the pathogenesis of atherosclerosis.Atherosclerotic plaques in humans are primarily composed of smooth muscle cells. This study investigates whether these plaques are monoclonal or polyclonal in origin. Using X-linked glucose-6-phosphate dehydrogenase (G6PD) in heterozygous females, researchers analyzed 30 plaques and 59 samples from four females. The results showed that fibrous caps of atheromatous plaques, even large ones, consist of cells producing a single enzyme type, while normal artery wall tissues contain a mixture of cell types. This suggests that atherosclerotic plaques are monoclonal, not a response to injury or healing. The monoclonal nature is likely due to mutations, possibly caused by chemical mutagens or viruses. Atherosclerosis is a progressive disease of major arteries, characterized by fibrous plaques composed mainly of smooth muscle cells surrounded by collagen. The study compared human and avian atherosclerotic plaques with responses to injury in mammalian aortas, leading to the hypothesis that atherosclerotic plaques arise from a different mechanism than injury repair. Cells in atherosclerotic plaques differ from normal artery wall cells in size, extracellular material composition, and lack of intercellular junctions, suggesting they may originate from a different cell population or be transformed cells. The study used G6PD isoenzymes to analyze enzyme patterns in plaques and normal tissues. Results showed that individual plaques had consistent enzyme patterns, indicating monoclonal origin. Analysis of 81 samples from 30 plaques and 59 normal tissues revealed that some plaques were predominantly of one enzyme type, while others were mixed. The data suggest that atherosclerotic plaques are monoclonal, possibly due to mutations. The study also found that the appearance of a monoclonal enzyme pattern in some normal artery wall samples may indicate early plaque formation. The study concludes that atherosclerotic plaques are monoclonal, likely due to mutations, and that factors such as chemical mutagens or viruses may be involved. The findings challenge the traditional injury-repair hypothesis and suggest that atherosclerosis may result from cell transformation rather than injury. The study highlights the importance of considering cell transformation in the pathogenesis of atherosclerosis.