LETTER TO THE EDITOR
Reply
Francesco Violi, MDa,
Luigi Iuliano, MD and
Garret A. FitzGerald, MD
a Istituto di I Clinica Medica, University La Sapienza, Viale del Policlinico, Rome 00185 Italy
francesco.violi{at}uniroma1.it
Cracowski et al. raise an important issue related to the putative biologic effect of F2-isoprostanes (iPs) in human coronary arteries after percutaneous transluminal coronary angioplasty (PTCA). We observed an increase of isoprostanes iPF2 -III and iPF2-VI in the coronary sinus immediately after PTCA and suggested that this elevation not only reflected reperfusion-mediated oxidative stress but could also play a role in the untoward effects of this procedure. In particular, iPs may facilitate platelet activation and coronary vasospasm, two phenomena that occur early after PTCA and are responsible for coronary thrombosis and arrhythmia.
Used as markers of oxidant stress, F2-iPs are increased not only in clinical settings associated with ischemia-reperfusion but also in settings characterized by chronic inflammation such as atherosclerosis, chronic bronchitis and systemic lupus erythematosus (1–3). The F2-iPs may also have biologic relevance because they enhance platelet response to the common agonists and elicit a vasomotor response. However, it is still unclear whether these effects can occur in clinical settings associated with enhanced oxidative stress. An in vitro study demonstrated that iPF2-III was not able to elicit platelet aggregation, but in a range of concentration between 10 nmol/l and 10 µmol/l increased the magnitude of platelet response to subthreshold concentrations of arachidonic acid, collagen and adenosine diphosphate (ADP) (4). Patients with diabetes and hypercholesterolemia show a significant correlation between iPF2-III and 1-dehydrothromboxane B2 values, suggesting a potential link between platelet aggregation and lipid peroxidation (5,6). This was corroborated by the concomitant decrease of iPF2-III and 11-dehydrothromboxane B2 in patients given 100 to 600 mg/d vitamin E. These data suggest that the circulating levels of iPF2-III may be relevant to clinical settings in which platelet activation and enhanced oxidative stress coexist. Because these two phenomena coincide after PTCA, it is conceivable that a link exists between them, taking into account that in some patients the circulating levels of iPF2-III after PTCA were close to 1 nmol/l. We agree with Cracowski and colleagues that the circulating levels of iPF2-III were likely too low to elicit a direct vasomotor response in the coronary circulation. However, values of the two isoprostane regioisomers measured specifically by us in the coronary sinus cannot be extrapolated to Morrow et al.’s (7) total isoprostane assay with PGF2 as internal standard. Even if it did give a quantitative impression of total iPs, this method is quantitatively imprecise, measuring a host of unresolved peaks. Similar amounts of one isoprostane, such as iPF2-III, which is not a very abundant one, suggests that an accurate estimate of total iPs in the coronary circulation would be much higher than in peripheral plasma. Also, it is very difficult to extrapolate from one iP to the effects and local concentration of myriad ones released at the site of free radical burst on the vascular wall.
Finally, it has never been studied, as in the case of platelet aggregation, whether iPF2-III is able to amplify the vasomotor response to other agonists. This effect should be studied in the future before concluding that the concentration of this isoprostane in the coronary circulation has no role in the vasospasm occurring after PTCA.
 |
References
|
|---|
1. Praticò D, Iuliano I, Mauriello A, et al. Localization of distinct F2-isoprostanes in human atherosclerotic lesions. J Clin Invest. 1997;100:2028–2034[Medline]
2. Iuliano L, Praticò D, Ferro D, et al. Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies. Blood. 1997;90:3931–3935[Abstract/Free Full Text]
3. Praticò D, Basili S, Vieri M, Cordova C, Violi F, Fitzgerald GA. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2-alpha-III, an index of oxidant stress. Am J Respir Crit Care Med. 1998;158:1709–1714[Abstract/Free Full Text]
4. Praticò D, Smyth EM, Violi F, FitzGerald GA. Local amplification of platelet function by 8-Epi-prostaglandin F2-alpha is not mediated by thromboxane receptor isoforms. J Biol Chem. 1996;271:14916–14924[Abstract/Free Full Text]
5. Davi G, Alessandrini P, Mezzetti A, et al. In vivo formation of 8-Epi-prostaglandin F2-alpha is increased in hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1997;17:3230–3235[Abstract/Free Full Text]
6. Davi G, Ciabattoni G, Consoli A, et al. In vivo formation of 8-iso-prostaglandin f2-alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation. 1999;99:224–229[Abstract/Free Full Text]
7. Morrow JD, Frei B, Longmire AW, et al. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: Smoking as a cause of oxidative damage. N Engl J Med. 1995;332:1198–1203[Abstract/Free Full Text]
|
Top
References