NITRIC OXIDE-DONATING STATINS EXERT BENEFICIAL EFFECTS ON ACUTE VASCULAR INFLAMMATION IN NORMOCHOLESTEROLEMIC RABBITS
Poster
Data di Pubblicazione:
2011
Citazione:
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) [10.1016/S1567-5688(11)70766-8].
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
R. Baetta, A.C. Granata, L. Arnaboldi, N. Ferri, S. Bellosta, A. Bonomo, D. Miglietta, P. Pfister, A. Corsini
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