Atherosclerotic plaque as a benign tumor?

Generation and Characterization of Human Smooth Muscle Cell Lines Derived From Atherosclerotic Plaque

“…40 -43 pdSMC2 were generally diploid with a variety of structural and numerical alterations, yet with no consistent chromosomal losses or gains; pdSMC1A were highly aneuploid, a ϪY, ϩ7, Ϫ13 population strongly emerging with passage in culture. The ϪY, ϩ7 genotype is a consistently reported feature of SMCs in atherosclerotic lesions 40,42,43 and has been observed in SMCs grown from atherosclerotic lesions as well as in SMC-positive areas of paraffin-embedded plaques. 40,42,43 Whether the predominant cytogenetic anomalies observed in the present studies contributed to the outgrowth of this population or are the consequence of other selective factors/stimuli is unknown.…”

“…The ϪY, ϩ7 genotype is a consistently reported feature of SMCs in atherosclerotic lesions 40,42,43 and has been observed in SMCs grown from atherosclerotic lesions as well as in SMC-positive areas of paraffin-embedded plaques. 40,42,43 Whether the predominant cytogenetic anomalies observed in the present studies contributed to the outgrowth of this population or are the consequence of other selective factors/stimuli is unknown. It is noteworthy that the aneuploidy observed at early passage in the pdSMC1A reflects the plaque origin of these cells rather than an artifact of tissue culture, since cultured normal adult and fetal (early-passage) SMCs and pdSMC2 are not aneuploid.…”

“…Whether the dedifferentiated phenotype is accessory or consequential to this extended life span is unknown. The prevalence of the ϩ7 genotype in plaque SMCs 40,42,43 prompts some degree of consideration of a possible role of a gene(s) located on chromosome 7 in atherogenesis. Several of these genes' products have been associated with SMC mitogenic/chemoattractant activity, differentiation, or vascular tone/contractility 14,17,36,47,54 -58 and include PDGF A, tropoelastin, AQP1/CHIP28, nitric oxide synthase, and the EGF receptor.…”

Genetic Instability, DNA Damage and Atherosclerosis

“…Consequently, an increase of SMC proliferation may take place, supporting the hypothesis of the plaque as a benign tumor. [21][22] Notably, Matturri et al 22 showed that unstable atherosclerotic plaque presented a variety of chromosomal abnormalities in carotid specimens. Conversely, stable plaque do not present those chromosomal abnormalities, supporting the hypothesis that genetic instability might be of particular importance in the evolution of the plaque.…”

“…[20][21][22] Noteworthy is the recurring presence of trisomy 7. The presence of a 7 extra chromosome is correlated with an overexpression of the gene located in this chromosome, such as the gene for the A-chain of Platelet-Derived Growth Factor, the MET-proto-oncogene, and receptor genes for Epidermal Growth Factor.…”