F-2-Isoprostanes are prostaglandin (PG) isomers formed in situ in cell membranes by peroxidation of arachidonic acid. 8-epi PGF(2 alpha) and IPF2 alpha-I are F-2-isoprostanes produced in humans which circulate in plasma and are excreted in urine. Measurement of F-2-isoprostanes may offer a sensitive, specific, and noninvasive method for measuring oxidant stress in clinical settings where reactive oxygen species are putatively involved. We determined whether isoprostanes were present in human atherosclerotic lesions, where lipid peroxidation is thought to occur in vivo. 8-epi PGF(2 alpha) ranged from 1.310-3.450 pmol/mu mol phospholipid in atherectomy specimens compared with 0.045-0.115 pmol/mu mol phospholipid (P < 0.001) in vascular tissue devoid of atherosclerosis. Corresponding values of IPF2 alpha-I were 5.6-13.8 vs. 0.16-0.44 pmol/mu mol phospholipid (P < 0.001). Levels of the two isoprostanes in vascular tissue were highly correlated (r = 0.80, P < 0.0001). Immunohistochemical studies confirmed that foam cells adjacent to the lipid necrotic core of the plaque were markedly positive for 8-epi PGF(2 alpha). These cells were also reactive with anti-CD68, and epitope specific for human monocyte/macrophages. 8-epi PGF(2 alpha) immunoreactivity was also detected in cells positive for anti-alpha-smooth muscle actin antibody, which specifically recognizes vascular smooth muscle cells. Our results indicate that 8-epi PGF(2 alpha) and IPF2 alpha-I, two distinct F-2-isoprostanes and markers of oxidative stress in vivo, are present in human atherosclerotic plaque. Quantitation of these chemically stable products of lipid peroxidation in target tissues, as well as in biological fluids, map aid in the rational development of antioxidant drugs in humans.

Pratico, D., Iuliano, L., Mauriello, A., Spagnoli, L.G., Lawson, J.A., Maclouf, J., et al. (1997). Localization of distinct F2-isoprostanes in human atherosclerotic lesions. THE JOURNAL OF CLINICAL INVESTIGATION, 100(8), 2028-2034.

Localization of distinct F2-isoprostanes in human atherosclerotic lesions

MAURIELLO, ALESSANDRO;SPAGNOLI, LUIGI GIUSTO;
1997

Abstract

F-2-Isoprostanes are prostaglandin (PG) isomers formed in situ in cell membranes by peroxidation of arachidonic acid. 8-epi PGF(2 alpha) and IPF2 alpha-I are F-2-isoprostanes produced in humans which circulate in plasma and are excreted in urine. Measurement of F-2-isoprostanes may offer a sensitive, specific, and noninvasive method for measuring oxidant stress in clinical settings where reactive oxygen species are putatively involved. We determined whether isoprostanes were present in human atherosclerotic lesions, where lipid peroxidation is thought to occur in vivo. 8-epi PGF(2 alpha) ranged from 1.310-3.450 pmol/mu mol phospholipid in atherectomy specimens compared with 0.045-0.115 pmol/mu mol phospholipid (P < 0.001) in vascular tissue devoid of atherosclerosis. Corresponding values of IPF2 alpha-I were 5.6-13.8 vs. 0.16-0.44 pmol/mu mol phospholipid (P < 0.001). Levels of the two isoprostanes in vascular tissue were highly correlated (r = 0.80, P < 0.0001). Immunohistochemical studies confirmed that foam cells adjacent to the lipid necrotic core of the plaque were markedly positive for 8-epi PGF(2 alpha). These cells were also reactive with anti-CD68, and epitope specific for human monocyte/macrophages. 8-epi PGF(2 alpha) immunoreactivity was also detected in cells positive for anti-alpha-smooth muscle actin antibody, which specifically recognizes vascular smooth muscle cells. Our results indicate that 8-epi PGF(2 alpha) and IPF2 alpha-I, two distinct F-2-isoprostanes and markers of oxidative stress in vivo, are present in human atherosclerotic plaque. Quantitation of these chemically stable products of lipid peroxidation in target tissues, as well as in biological fluids, map aid in the rational development of antioxidant drugs in humans.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/08 - Anatomia Patologica
English
Con Impact Factor ISI
atherosclerosis; oxidative stress; lipid peroxidation; isoprostanes
Pratico, D., Iuliano, L., Mauriello, A., Spagnoli, L.G., Lawson, J.A., Maclouf, J., et al. (1997). Localization of distinct F2-isoprostanes in human atherosclerotic lesions. THE JOURNAL OF CLINICAL INVESTIGATION, 100(8), 2028-2034.
Pratico, D; Iuliano, L; Mauriello, A; Spagnoli, Lg; Lawson, J; Maclouf, J; Violi, F; Fitzgerald, G
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/53678
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact