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dc.contributor.authorMcLoughlin, D.
dc.contributor.authorMcGuinness, J.
dc.contributor.authorByrne, J.
dc.contributor.authorTerzo, E.
dc.contributor.authorHuuskonen, V.
dc.contributor.authorMcAllister, H.
dc.contributor.authorBlack, A.
dc.contributor.authorKearney, S.
dc.contributor.authorKay, E.
dc.contributor.authorHill, A. D. K.
dc.contributor.authorDietz, H. C.
dc.contributor.authorRedmond, J. M.
dc.date.accessioned2018-09-20T16:17:22Z
dc.date.available2018-09-20T16:17:22Z
dc.date.issued2011-09-12
dc.identifier.citationMcLoughlin, D. McGuinness, J.; Byrne, J.; Terzo, E.; Huuskonen, V.; McAllister, H.; Black, A.; Kearney, S.; Kay, E.; Hill, A. D. K.; Dietz, H. C.; Redmond, J. M. (2011). Pravastatin reduces marfan aortic dilation. Circulation 124 (11), S168-S173
dc.identifier.issn0009-7322,1524-4539
dc.identifier.urihttp://hdl.handle.net/10379/12825
dc.description.abstractBackground-The sequelae of aortic root dilation are the lethal consequences of Marfan syndrome. The root dilation is attributable to an imbalance between deposition of matrix elements and metalloproteinases in the aortic medial layer as a result of excessive transforming growth factor-beta signaling. This study examined the efficacy and mechanism of statins in attenuating aortic root dilation in Marfan syndrome and compared effects to the other main proposed preventative agent, losartan. Methods and Results-Marfan mice heterozygous for a mutant allele encoding a cysteine substitution in fibrillin-1 (C1039G) were treated daily from 6 weeks old with pravastatin 0.5g/L or losartan 0.6 g/L. The end points of aortic root diameter (n = 25), aortic thickness, and architecture (n = 10), elastin volume (n = 5), dp/dtmax (maximal rate of change of pressure) (cardiac catheter; n = 20), and ultrastructural analysis with stereology (electron microscopy; n = 5) were examined. The aortic root diameters of untreated Marfan mice were significantly increased in comparison to normal mice (0.161 +/- 0.001 cm vs 0.252 +/- 0.004 cm; P < 0.01). Pravastatin (0.22 +/- 0.003 cm; P < 0.01) and losartan (0.221 +/- 0.004 cm; P < 0.01) produced a significant reduction in aortic root dilation. Both drugs also preserved elastin volume within the medial layer (pravastatin 0.23 +/- 0.02 and losartan 0.29 +/- 0.03 vs untreated Marfan 0.19 +/- 0.02; P = 0.01; normal mice 0.27 +/- 0.02). Ultrastructural analysis showed a reduction of rough endoplasmic reticulum in smooth muscle cells with pravastatin (0.022 +/- 0.004) and losartan (0.013 +/- 0.001) compared to untreated Marfan mice (0.035 +/- 0.004; P < 0.01). Conclusions-Statins are similar to losartan in attenuating aortic root dilation in a mouse model of Marfan syndrome. They appear to act through reducing the excessive protein manufacture by vascular smooth muscle cells, which occurs in the Marfan aorta. As a drug that is relatively well-tolerated for long-term use, it may be useful clinically. (Circulation. 2011; 124[suppl 1]: S168-S173.)
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.relation.ispartofCirculation
dc.subjectaneurysm
dc.subjectaorta
dc.subjectpathology
dc.subjectremodeling
dc.subjectvessels
dc.subjectsmooth-muscle-cells
dc.subjectmouse model
dc.subjectpathogenesis
dc.subjectlosartan
dc.subjectaneurysm
dc.subjectdisease
dc.subjectmetalloproteinases
dc.subjectinflammation
dc.subjectprevention
dc.subjectevents
dc.titlePravastatin reduces marfan aortic dilation
dc.typeArticle
dc.identifier.doi10.1161/circulationaha.110.012187
dc.local.publishedsourcehttps://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.110.012187
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