Molecular epidemiology of atherosclerosis

Silvio De Flora, Alberto Izzotti, Debra Walsh, Paolo Degan, Gian Luigi Petrilli, Joellen Lewtas

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

It has been hypothesized that mutational events may be involved in the atherogenetic process and that at least a portion of atherosclerotic plaques may develop according to an initiation-promotion process of arterial smooth muscle cells, akin to benign tumors. We conducted a study to evaluate the occurrence of oxidative DNA damage and formation of DNA adducts in human atherosclerotic lesions and to assess the relationships of these promutagenic alterations with exposure to atherogenic risk factors. Pure DNA was extracted from the tunica media (composed mainly of smooth muscle cells) of abdominal aorta fragments taken at surgery from 85 patients suffering from severe atherosclerotic lesions. DNA adducts were detected by synchronous fluorescence spectrophotometry and 32P postlabeling after enrichment of adducts with either butanol or nuclease P1. 8-Hydroxy-2'-deoxyguanosine (8- OH-dG), a typical indicator of oxidative DNA damage, was measured by HPLC/electrochemical detection. A complete questionnaire reporting general, clinical, and laboratory characteristics was available for each patient. All 84 samples tested by 32P postlabeling were positive by displaying the presence of diagonal radioactive zones and up to 9 individual DNA adducts. Of 52 samples tested, 32 (61.5%) yielded typical positive signals at synchronous fluorescence spectrophotometry. All but one of 39 samples tested had very high levels of 8-OH-dG, thus showing a remarkable oxidative DNA damage. Statistically significant correlations were found between the levels of molecular biomarkers and atherogenic risk factors including age, number of currently smoked cigarettes, ratio of total-to-high density lipoprotein blood cholesterol, blood triglycerides, and blood pressure. The DNA alterations detected in our study may be only one component of the genetic basis of atherogenesis. Moreover, no causal role in the atherogenetic process can be inferred from our results. However, DNA alterations, including oxidative damage and adduction of reactive molecules of either endogenous or exogenous source, were systematically present in the smooth muscle cells of human atherosclerotic lesions and their intensity was significantly correlated with the occurrence of atherogenic risk factors in the patients studied.

Original languageEnglish
Pages (from-to)1021-1031
Number of pages11
JournalFASEB Journal
Volume11
Issue number12
Publication statusPublished - Oct 1997

Fingerprint

DNA adducts
molecular epidemiology
Molecular Epidemiology
DNA Adducts
fluorescence emission spectroscopy
atherosclerosis
lesions (animal)
DNA damage
smooth muscle
myocytes
DNA Damage
Smooth Muscle Myocytes
Atherosclerosis
risk factors
Fluorescence Spectrometry
DNA
endogenous sources
exogenous sources
Tunica Media
Muscle

Keywords

  • Aging
  • Cigarette smoke
  • DNA adducts
  • Dyslipidosis
  • Hypertension
  • Oxidative DNA damage
  • Smooth muscle cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

De Flora, S., Izzotti, A., Walsh, D., Degan, P., Petrilli, G. L., & Lewtas, J. (1997). Molecular epidemiology of atherosclerosis. FASEB Journal, 11(12), 1021-1031.

Molecular epidemiology of atherosclerosis. / De Flora, Silvio; Izzotti, Alberto; Walsh, Debra; Degan, Paolo; Petrilli, Gian Luigi; Lewtas, Joellen.

In: FASEB Journal, Vol. 11, No. 12, 10.1997, p. 1021-1031.

Research output: Contribution to journalArticle

De Flora, S, Izzotti, A, Walsh, D, Degan, P, Petrilli, GL & Lewtas, J 1997, 'Molecular epidemiology of atherosclerosis', FASEB Journal, vol. 11, no. 12, pp. 1021-1031.
De Flora S, Izzotti A, Walsh D, Degan P, Petrilli GL, Lewtas J. Molecular epidemiology of atherosclerosis. FASEB Journal. 1997 Oct;11(12):1021-1031.
De Flora, Silvio ; Izzotti, Alberto ; Walsh, Debra ; Degan, Paolo ; Petrilli, Gian Luigi ; Lewtas, Joellen. / Molecular epidemiology of atherosclerosis. In: FASEB Journal. 1997 ; Vol. 11, No. 12. pp. 1021-1031.
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