In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 3 ( 2022-3-4), p. e1010059-
Abstract:
Vascular Ehlers-Danlos syndrome is a rare inherited disorder caused by genetic variants in type III collagen. Its prognosis is especially hampered by unpredictable arterial ruptures and there is no therapeutic consensus. We created a knock-in Col3a1 +/G182R mouse model and performed a complete genetic, molecular and biochemical characterization. Several therapeutic strategies were also tested. Col3a1 +/G182R mice showed a spontaneous mortality caused by thoracic aortic rupture that recapitulates the vascular Ehlers-Danlos syndrome with a lower survival rate in males, thin non-inflammatory arteries and an 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 vascular Ehlers-Danlos syndrome.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010059
DOI:
10.1371/journal.pgen.1010059.g001
DOI:
10.1371/journal.pgen.1010059.g002
DOI:
10.1371/journal.pgen.1010059.g003
DOI:
10.1371/journal.pgen.1010059.g004
DOI:
10.1371/journal.pgen.1010059.g005
DOI:
10.1371/journal.pgen.1010059.g006
DOI:
10.1371/journal.pgen.1010059.g007
DOI:
10.1371/journal.pgen.1010059.g008
DOI:
10.1371/journal.pgen.1010059.g009
DOI:
10.1371/journal.pgen.1010059.s001
DOI:
10.1371/journal.pgen.1010059.s002
DOI:
10.1371/journal.pgen.1010059.s003
DOI:
10.1371/journal.pgen.1010059.s004
DOI:
10.1371/journal.pgen.1010059.s005
DOI:
10.1371/journal.pgen.1010059.s006
DOI:
10.1371/journal.pgen.1010059.s007
DOI:
10.1371/journal.pgen.1010059.s008
DOI:
10.1371/journal.pgen.1010059.s009
DOI:
10.1371/journal.pgen.1010059.s010
DOI:
10.1371/journal.pgen.1010059.s011
DOI:
10.1371/journal.pgen.1010059.s012
DOI:
10.1371/journal.pgen.1010059.s013
DOI:
10.1371/journal.pgen.1010059.s014
DOI:
10.1371/journal.pgen.1010059.s015
DOI:
10.1371/journal.pgen.1010059.s016
DOI:
10.1371/journal.pgen.1010059.s017
DOI:
10.1371/journal.pgen.1010059.s018
DOI:
10.1371/journal.pgen.1010059.s019
DOI:
10.1371/journal.pgen.1010059.s020
DOI:
10.1371/journal.pgen.1010059.r001
DOI:
10.1371/journal.pgen.1010059.r002
DOI:
10.1371/journal.pgen.1010059.r003
DOI:
10.1371/journal.pgen.1010059.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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