title: Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost.
abstract: 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-PGF(₂α) excretion rate, as in vivo indexes 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-PGF(₂α) [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-PGF(₂α) 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.
authors.affiliation: Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Lessiani
authors.forename: Natale
authors.initials: N
authors.lastname: Vazzana
authors.forename: Chiara
authors.initials: C
authors.lastname: Cuccurullo
authors.forename: Dario
authors.initials: D
authors.lastname: Di Michele
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Laurora
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sgrò
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Ruscio
authors.forename: Emilio
authors.initials: E
authors.lastname: Simeone
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Di Iorio
authors.forename: Stefano
authors.initials: S
authors.lastname: Lattanzio
authors.forename: Rossella
authors.initials: R
authors.lastname: Liani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology; D023201:CD40 Ligand / Q000097:blood; D016009:Chi-Square Distribution; D016638:Critical Illness; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D007262:Infusions, Intravenous; D007511:Ischemia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000652:urine; D007558:Italy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost; D016285:Iloprost; D001241:Aspirin