Counter-regulation by atorvastatin of gene modulations induced by L-NAME hypertension is associated with vascular protection
| Autor: | Liliane Louedec, Sophie Nadaud, Frédérique Capron, Florent Soubrier, Morgan Dupuis, Jean-Baptiste Michel, Isabelle Brocheriou, Mounsif Haloui |
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| Přispěvatelé: | Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Statin Physiology medicine.drug_class Atorvastatin [SDV]Life Sciences [q-bio] Nitric oxide Biological pathway chemistry.chemical_compound Internal medicine medicine Animals Pyrroles Aorta Pharmacology biology Cell growth Transforming growth factor beta Rats Inbred F344 Rats Nitric oxide synthase Endocrinology NG-Nitroarginine Methyl Ester chemistry Gene Expression Regulation Heptanoic Acids Hypertension biology.protein Molecular Medicine Endothelium Vascular Intracellular medicine.drug |
| Zdroj: | Vascular Pharmacology Vascular Pharmacology, 2009, 51 (4), pp.253-261. ⟨10.1016/j.vph.2009.06.011⟩ |
| ISSN: | 1537-1891 |
| DOI: | 10.1016/j.vph.2009.06.011⟩ |
| Popis: | Statins, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, protect against deleterious effects of chronic nitric oxide inhibition. We aimed at determining the genes and pathways involved in the protective effect of statin treatment during hypertension. Chronic inhibition of nitric oxide synthesis by Nω-nitro- l -arginine methyl ester (L-NAME) induced accelerated hypertension which was slightly reduced by cotreatment with atorvastatin (100 mg/kg/day). Gene expression profile of aortic media was strongly modified by atorvastatin cotreatment which prevented modulation of many genes regulated by L-NAME administration (described in Dupuis, M., Soubrier, F., Brocheriou, I., Raoux, S., Haloui, M., Louedec, L., Michel, J.B., Nadaud, S., 2004. Profiling of aortic smooth muscle cell gene expression in response to chronic inhibition of nitric oxide synthase in rats. Circulation 110, 867–873). The functional classification of these genes highlighted several major biological pathways modulated in aortic media by atorvastatin: effectors involved in smooth muscle tone; extracellular matrix; intracellular mediators of cell proliferation. Moreover, atorvastatin partially prevented arterial wall thickening, TGF-β pathway activation, MCP-1 induction and smooth muscle cell proliferation induced by L-NAME treatment although blood pressure was only slightly reduced, suggesting mechanisms independent of blood pressure levels. The induction of PPARalpha mRNA expression by atorvastatin in L-NAME treated rats also suggests that this pathway could participate in the protective effect. In conclusion, our data show that atorvastatin specifically antagonizes a set of genes modulated by L-NAME-induced accelerated hypertension. |
| Databáze: | OpenAIRE |
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