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 Printable version |
Marfan syndrome, magnesium status and medical prevention of cardiovascular complications by hemodynamic treatments and antisense gene therapy |
Magnesium Research. Volume 16, Number 1, 59-64, March 2003, ORIGINAL ARTICLE
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 Free Article
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Author(s) : S. Igondjo‐Tchen, N. Pagès, P. Bac, G. Godeau, J. Durlach |
Summary : The medical management of Marfan Syndrome (MFS) mainly relies on early prevention of the aortic complications. Hemodynamic treatments try to diminish the forcefulness of cardiac contractions and to reduce blood pressure: for example long term administration of propranolol may significantly reduce the rate of increase in aortic ratio (aortic diameter\\expected aortic diameter). Retardation of aortic dilatation may be most often observed by early treatment started when the baseline end‐diastolic aortic root diameter is <\; 40 mm. It seems better to use β‐blockers without intrinsic sympathomimetic activity. Successful acceptance of β‐blockers may be limited by side‐effects, but the efficiency of alternative hypotensive agents (calcium channel inhibitors, ACE inhibitors) is not yet validated. Gene therapy might constitute an etiologic specific treatment of MFS. FBN1‐RZ1 hammerhead antisense ribozyme is able to suppress expression of the mutant FBN1 allele. The use of ribozymes as systemic therapeutic agents will depend on efficient delivery to its target, but the various proposed vectors raise yet unsolved problems. A hydrogel angioplasty balloon might be a possible vector for delivering an antisense ribozyme in the aortic wall specifically. Ribozymes ‐as deoxyribonucleotides‐ may be taken up by tissue upon local application. Further research should study
ex vivo local application of antisense ribozyme on human aortic wall, before assessing
in vivo efficiency and tolerance of this aortic local vectorisation. It is always necessary to maintain a balanced magnesium intake in patients with MFS. Firstly to prevent the multiple noxious effects of magnesium deficiency on cardiovascular targets. Secondly to ensure the best efficiency and the least toxicity of the hemodynamic drugs used as long term prophylactic treatment for cardiovascular complications and of the etiologic antisense magnesium‐dependent gene therapy, in the future. |
Keywords : Marfan Syndrome, magnesium, β‐ blockers, aortic dilatation, antisense ribozyme, hammerhead ribozyme, gene therapy, hydrogel coated angioplasty, balloon |
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