Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers Danlos syndrome

Legrand, A.; Guery, C.; Faugeroux, J.; Fontaine, E.; Gianfermi, A.; Ferreira, I.; Verpont, M.-c.; Adham, S.; Mirault, T.; Hadchouel, J.; Jeunemaitre, X.

doi:10.1101/2021.06.12.448202

bioRxiv · 10.1101/2021.06.12.448202

Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers Danlos syndrome

Legrand, A.·Guery, C.·Faugeroux, J.·Fontaine, E.·Gianfermi, A.·Ferreira, I.·Verpont, M.-c.·Adham, S.·Mirault, T.·Hadchouel, J.·Jeunemaitre, X.

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Abstract

We created a knock-in Col3a1+/G182R mouse model with spontaneous mortality caused by thoracic aortic rupture that recapitulates a rare vascular genetic disease of type III collagen, the vascular Ehlers-Danlos syndrome (vEDS). Investigation of this model showed lower survival rate in males caused by aortic rupture, thin non-inflammatory arteries and altered arterial collagen. Transcriptomic analysis of aortas showed upregulation of genes related to inflammation and cell stress response. Compared to water, survival rate of Col3a1+/G182R mice was not affected by beta-blockers (propranolol or celiprolol). Two other vasodilating anti-hypertensive agents (hydralazine, amlodipine) gave opposite results on aortic rupture and mortality rate. There was a spectacular beneficial effect of losartan, reversed by the cessation of its administration, and a marked deleterious effect of exogenous angiotensin II. These results suggest that blockade of the renin angiotensin system should be tested as a first-line medical therapy in patients with vEDS.

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Legrand, A., Guery, C., Faugeroux, J., Fontaine, E., Gianfermi, A., Ferreira, I., Verpont, M.-c., Adham, S., Mirault, T., Hadchouel, J., Jeunemaitre, X.. 2021-06-12. Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers Danlos syndrome. https://doi.org/10.1101/2021.06.12.448202

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