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Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis.
Cardiovasc Res. 2012 Jun 01; 94(3):428-38.CR

Abstract

AIMS

The aim of the present study was to assess whether the addition of a nitric oxide (NO)-donating moiety to atorvastatin enhances anti-inflammatory and anti-atherogenic effects in an animal model of endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis.

METHODS AND RESULTS

Low-density lipoprotein receptor (LDLR)(-/-) mice kept on a high-fat diet (HFD) for 16 weeks underwent photochemical injury to the femoral artery with the local production of oxygen radicals. HFD markedly enhanced cholesterol, inflammatory biomarkers in plasma and in the femoral arterial wall, and atherosclerotic lesions in the aortic arch; inflammation and atherosclerosis were further increased by photochemically generated oxygen radicals. Treatment with the NO-donating atorvastatin NCX 6560 (11.7 mg/kg) was significantly more effective than atorvastatin (10 mg/kg) in reducing the following parameters: lipid-rich lesions in the aortic arch (surface covered: atorvastatin = 24 ± 5%; NCX 6560 = 14.7 ± 3.9%; P< 0.05); the production of radical oxygen species in the aorta (dichlorofluorescein fluorescence intensity per milligram of protein: atorvastatin = 2419 ± 136.7; NCX 6560 = 1766 ± 161.2; P< 0.05); femoral artery intima/media thickness (atorvastatin = 1.2 ± 0.11; NCX 6560 = 0.3 ± 0.14; P< 0.05); circulating interleukin-6 (atorvastatin = 34.3 ± 6.8 pg/mL; NCX 6560 = 17.7 ± 14.4 pg/mL; P< 0.05); and matrix metalloproteinase 2 in the arterial wall (atorvastatin = 55.2 ± 1.9 ng/µg of proteins; NCX 6560 = 45.8 ± 2.6 ng/µg of proteins; P < 0.05).

CONCLUSION

In conditions of severe endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis, atorvastatin, even at high doses, displays suboptimal anti-atherogenic and anti-inflammatory effects, while the addition of a NO-donating property confers enhanced anti-atherogenic and anti-inflammatory effects.

Authors+Show Affiliations

Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Via E. dal Pozzo, 06126 Perugia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22362817

Citation

Momi, Stefania, et al. "Nitric Oxide Enhances the Anti-inflammatory and Anti-atherogenic Activity of Atorvastatin in a Mouse Model of Accelerated Atherosclerosis." Cardiovascular Research, vol. 94, no. 3, 2012, pp. 428-38.
Momi S, Monopoli A, Alberti PF, et al. Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis. Cardiovasc Res. 2012;94(3):428-38.
Momi, S., Monopoli, A., Alberti, P. F., Falcinelli, E., Corazzi, T., Conti, V., Miglietta, D., Ongini, E., Minuz, P., & Gresele, P. (2012). Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis. Cardiovascular Research, 94(3), 428-38. https://doi.org/10.1093/cvr/cvs100
Momi S, et al. Nitric Oxide Enhances the Anti-inflammatory and Anti-atherogenic Activity of Atorvastatin in a Mouse Model of Accelerated Atherosclerosis. Cardiovasc Res. 2012 Jun 1;94(3):428-38. PubMed PMID: 22362817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis. AU - Momi,Stefania, AU - Monopoli,Angela, AU - Alberti,Paolo Francesco, AU - Falcinelli,Emanuela, AU - Corazzi,Teresa, AU - Conti,Valentina, AU - Miglietta,Daniela, AU - Ongini,Ennio, AU - Minuz,Pietro, AU - Gresele,Paolo, Y1 - 2012/02/23/ PY - 2012/2/25/entrez PY - 2012/3/1/pubmed PY - 2012/9/18/medline SP - 428 EP - 38 JF - Cardiovascular research JO - Cardiovasc Res VL - 94 IS - 3 N2 - AIMS: The aim of the present study was to assess whether the addition of a nitric oxide (NO)-donating moiety to atorvastatin enhances anti-inflammatory and anti-atherogenic effects in an animal model of endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis. METHODS AND RESULTS: Low-density lipoprotein receptor (LDLR)(-/-) mice kept on a high-fat diet (HFD) for 16 weeks underwent photochemical injury to the femoral artery with the local production of oxygen radicals. HFD markedly enhanced cholesterol, inflammatory biomarkers in plasma and in the femoral arterial wall, and atherosclerotic lesions in the aortic arch; inflammation and atherosclerosis were further increased by photochemically generated oxygen radicals. Treatment with the NO-donating atorvastatin NCX 6560 (11.7 mg/kg) was significantly more effective than atorvastatin (10 mg/kg) in reducing the following parameters: lipid-rich lesions in the aortic arch (surface covered: atorvastatin = 24 ± 5%; NCX 6560 = 14.7 ± 3.9%; P< 0.05); the production of radical oxygen species in the aorta (dichlorofluorescein fluorescence intensity per milligram of protein: atorvastatin = 2419 ± 136.7; NCX 6560 = 1766 ± 161.2; P< 0.05); femoral artery intima/media thickness (atorvastatin = 1.2 ± 0.11; NCX 6560 = 0.3 ± 0.14; P< 0.05); circulating interleukin-6 (atorvastatin = 34.3 ± 6.8 pg/mL; NCX 6560 = 17.7 ± 14.4 pg/mL; P< 0.05); and matrix metalloproteinase 2 in the arterial wall (atorvastatin = 55.2 ± 1.9 ng/µg of proteins; NCX 6560 = 45.8 ± 2.6 ng/µg of proteins; P < 0.05). CONCLUSION: In conditions of severe endothelial dysfunction, systemic peroxidation and inflammation, and accelerated atherosclerosis, atorvastatin, even at high doses, displays suboptimal anti-atherogenic and anti-inflammatory effects, while the addition of a NO-donating property confers enhanced anti-atherogenic and anti-inflammatory effects. SN - 1755-3245 UR - https://www.unboundmedicine.com/medline/citation/22362817/Nitric_oxide_enhances_the_anti_inflammatory_and_anti_atherogenic_activity_of_atorvastatin_in_a_mouse_model_of_accelerated_atherosclerosis_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvs100 DB - PRIME DP - Unbound Medicine ER -