Introduction: Evidence has emerged suggesting that polymorphonuclear leukocytes (PMN) can make important contributions to vascular inflammatory processes underlying atherogenesis, thus representing new possible targets for atheroprotection. Nitric oxide (NO)-donating statins are a new class of drugs aimed to combine the effects of statins with the atheroprotective properties of NO (PNAS 2004;101: 8497–8502). Aim:We investigated the effects of a short-term treatment with two NO-donating derivatives of atorvastatin, NCX 6560 (successfully investigated in early clinical development; Circulation. 2010;122:A14267) and NCX 616, as compared to atorvastatin, on PMN infiltration in rabbit carotids subjected to perivascular collar placement, a model of acute arterial inflammation related to atherogenesis. Methods: Chow-fed rabbits (n = 10/group) received a daily oral dose of vehicle or experimental compounds (equivalent to 5 mg/kg/day atorvastatin) for 6 days. Collars were implanted after the last dose of treatment. Twenty-four hours later arteries were removed, immunostained for PMN, and measured by image analysis. Results: Collared carotids from the control group had a high content of PMN. Unlike atorvastatin, which did not influence the average value of PMN-positivearea compared to control, both the NO-donating statins NCX 616 and NCX 6560, which retain the inhibitory activity of atorvastatin on HMG-CoA reductase and release bioactive NO, reduced PMN infiltration of about 40% (p < 0.05) and 35% vs. control, respectively. Conclusions: NO-donating derivatives of atorvastatin exert, in addition to the effect of statin, additional beneficial effects on vascular inflammation, thus supporting a pharmacological rationale for their clinical development.
NITRIC OXIDE-DONATING STATINS EXERT BENEFICIAL EFFECTS ON ACUTE VASCULAR INFLAMMATION IN NORMOCHOLESTEROLEMIC RABBITS / R. Baetta, A.C. Granata, L. Arnaboldi, N. Ferri, S. Bellosta, A. Bonomo, D. Miglietta, P. Pfister, A. Corsini. - In: ATHEROSCLEROSIS SUPPLEMENTS. - ISSN 1567-5688. - 12:1(2011 Jun), pp. 160-160. ((Intervento presentato al 79. convegno Congress of the European-Atherosclerosis-Society (EAS) tenutosi a Gothenburg, Sweden nel 2011.
|Titolo:||NITRIC OXIDE-DONATING STATINS EXERT BENEFICIAL EFFECTS ON ACUTE VASCULAR INFLAMMATION IN NORMOCHOLESTEROLEMIC RABBITS|
BAETTA, ROBERTA (Primo)
GRANATA, AGNESE CATERINA (Secondo)
CORSINI, ALBERTO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||giu-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S1567-5688(11)70766-8|
|Appare nelle tipologie:||01 - Articolo su periodico|