Characterization of doxycycline-mediated inhibition of Marfan syndrome-associated aortic dilation by multiphoton microscopy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 04 2020
28 04 2020
Historique:
received:
17
12
2019
accepted:
17
03
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
7
1
2021
Statut:
epublish
Résumé
Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root widening and aneurysm if unmanaged. We have previously reported doxycycline, a nonselective matrix metalloproteinases (MMPs) inhibitor, to attenuate aortic root widening and improve aortic contractility and elasticity in MFS mice. We were also first to use multiphoton microscopy, a non-invasive and label-free imaging technique, to quantify and link the aortic ultrastructure to possible changes in the skin dermis. Here, we aimed to assess the effects of long-term doxycycline treatment on the aortic ultrastructure and skin dermis of MFS mice through immunohistochemical evaluation and quantification of elastic and collagen content and morphology using multiphoton microscopy. Our results demonstrate a rescue of aortic elastic fiber fragmentation and disorganization accompanied by a decrease in MMP-2 and MMP-9 expression within the aortic wall in doxycycline-treated MFS mice. At 12 months of age, reduced skin dermal thickness was observed in both MFS and control mice, but only dermal thinning in MFS mice was rescued by doxycycline treatment. MMP-2 and MMP-9 expression was reduced in the skin of doxycycline-treated MFS mice. A decrease in dermal thickness was found to be positively associated with increased aortic root elastin disorganization and wall thickness. Our findings confirm the beneficial effects of doxycycline on ultrastructural properties of aortic root as well as on skin elasticity and structural integrity in MFS mice.
Identifiants
pubmed: 32346027
doi: 10.1038/s41598-020-64071-8
pii: 10.1038/s41598-020-64071-8
pmc: PMC7188819
doi:
Substances chimiques
Doxycycline
N12000U13O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7154Subventions
Organisme : NHLBI NIH HHS
ID : R15 HL145646
Pays : United States
Organisme : CIHR
ID : MOP-111266
Pays : Canada
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