Chromosomal damage and atherosclerosis. A protective effect from simvastatin.

Abstract

In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage. Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration. Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82+/-2.1 vs. 4.65+/-2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage. Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients. In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity. Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque.

• Authors: Franco Pernice, Fulvio Floccari, Chiara Caccamo, Nadia Belghity, Stefania Mantuano, Maria Elisa Pacilè, Adolfo Romeo, Lorena Nostro, Antonio Barillà, Eleonora Crascì, Nicola Frisina, Michele Buemi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 532 Issue 3 Pg. 223-9 (Feb 27 2006) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16483569 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Simvastatin

Topics

• Atherosclerosis (blood, genetics, pathology)
• Carotid Arteries (diagnostic imaging, pathology)
• Cells, Cultured
• Chromosome Aberrations (drug effects)
• Dose-Response Relationship, Drug
• Female
• Hemodiafiltration
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Kidney Failure, Chronic (blood, genetics, therapy)
• Lymphocytes (drug effects)
• Male
• Middle Aged
• Mitotic Index
• Simvastatin (pharmacology)
• Sister Chromatid Exchange (drug effects)
• Ultrasonography