Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: Beneficial effects of iloprost

Gianfranco Lessiani; Natale Vazzana; Chiara Cuccurullo; Dario Di Michele; Giuseppe Laurora; Giuseppe Sgrò; Paolo Di Ruscio; Emilio Simeone; Pierangelo Di Iorio; Stefano Lattanzio; Rossella Liani; Elisabetta Ferrante; Giovanni Davì

doi:10.1160/TH10-07-0499

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(02): 321-328
DOI: 10.1160/TH10-07-0499

Platelets and Blood Cells

Schattauer GmbH

Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: Beneficial effects of iloprost

Authors

Gianfranco Lessiani^*

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy
Natale Vazzana^*

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy
Chiara Cuccurullo

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy
Dario Di Michele

²Internal Medicine, Teramo Civil Hospital, Teramo, Italy
Giuseppe Laurora

³Angiology Unit, “Pierangeli” Clinic, Pescara, Italy
Giuseppe Sgrò

⁴Internal Medicine, Castel di Sangro Civil Hospital, Castel di Sangro, Italy
Paolo Di Ruscio

³Angiology Unit, “Pierangeli” Clinic, Pescara, Italy
Emilio Simeone

⁵Geriatrics Unit, Casoli Civil Hospital, Casoli, Italy
Pierangelo Di Iorio

⁶Internal Medicine, Atessa Civil Hospital, Atessa, Italy
Stefano Lattanzio

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy
Rossella Liani

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy
Elisabetta Ferrante

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy
Giovanni Davì

¹Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Chieti, Italy

Abstract

Summary

Platelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB2 and 8-iso-PGF2α excretion rate, as in vivoindexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB2 [499 (277 – 807) vs. 380 (189 – 560) pg/mg creatinine, p < 0.0001] and 8-iso-PGF2α [533 (316 – 842) vs. 334 (196 – 540) pg/mg creatinine, p < 0.0001] as well as plasma sCD40L [1540 (1005 – 3015) vs. 948 (845 – 2030) pg/ml, p < 0.0001]. Furthermore, a significant increase in plasma nitrate plus nitrite levels has been observed [26.8 (18.8 – 35.9) vs. 43.7 (33.0 – 75.5) μM, p < 0.0001]. A significant direct correlation was also found between urinary 8-iso-PGF2α and 11-dehydro-TXB2 before and after iloprost treatment (Rho = 0.695, p < 0.0001). In conclusion, we report that a short-term course of iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.

Keywords

Platelet - inflammation - iloprost - oxidative stress - endothelial dysfunction - critical limb ischaemia

Full Text

References

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