Résumé:
The present invention refers to a method for the prevention or the treatment of a
thoracic aortic aneurysm (TAA) in a subject, comprising administering a blocker of a new
identified target of the nitric oxide (NO)¿methalloproteinase pathway.
In addition, the invention further provides an in vitro method wherein specific
biomarkers are used for identifying human subjects at risk of developing a disease
causing thoracic aortic aneurysm (TAA). This method comprises measuring the expression
pattern or level of specific NO¿metalloproteinase pathway components and the
expression pattern of some metalloproteinase substrates.
Lastly, the present invention refers to screening methods for identifying compounds
useful for the treatment, prevention or inhibition of a TAA.
This invention apply to patients suffering from (i) bicuspid aortic valve; (ii) a syndromic
thoracic aortic aneurysm (TAA) such as Marfan Syndrome (MFS), vascular Ehlers Danlos,
Loeys Dietz Syndrome (Types 1 and 2), and Familial thoracic aortic aneurysm and
dissection (familial TAAD); (iii) a non¿syndromic TAA; or (iv) any other disease associated
with an aortopathy triggered by the metalloproteinase deficiency described in the
invention and based on the results obtained by the inventors which represent a
substantial advance in understanding of the pathogenesis and molecular mediators
underlying aortic diseases