Label-free optical biomarkers detect early calcific aortic valve disease in a wild-type mouse model.
Calcific aortic valve disease
Two-photon excited fluorescence microscopy
Valve calcification
Wild-type mouse model
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
11 12 2020
11 12 2020
Historique:
received:
21
08
2020
accepted:
08
11
2020
entrez:
14
12
2020
pubmed:
15
12
2020
medline:
2
2
2021
Statut:
epublish
Résumé
Calcific aortic valve disease (CAVD) pathophysiology is a complex, multistage process, usually diagnosed at advanced stages after significant anatomical and hemodynamic changes in the valve. Early detection of disease progression is thus pivotal in the development of prevention and mitigation strategies. In this study, we developed a diet-based, non-genetically modified mouse model for early CAVD progression, and explored the utility of two-photon excited fluorescence (TPEF) microscopy for early detection of CAVD progression. TPEF imaging provides label-free, non-invasive, quantitative metrics with the potential to correlate with multiple stages of CAVD pathophysiology including calcium deposition, collagen remodeling and osteogenic differentiation. Twenty-week old C57BL/6J mice were fed either a control or pro-calcific diet for 16 weeks and monitored via echocardiography, histology, immunohistochemistry, and quantitative polarized light imaging. Additionally, TPEF imaging was used to quantify tissue autofluorescence (A) at 755 nm, 810 nm and 860 nm excitation, to calculate TPEF 755-860 ratio (A Pro-calcific mice showed evidence of lipid deposition at 4 weeks and calcification at 16 weeks at the valve commissures. The valves of pro-calcific mice also showed positive expression for markers of osteogenic differentiation, myofibroblast activation, proliferation, inflammatory cytokines and collagen remodeling. Pro-calcific mice exhibited lower TPEF autofluorescence ratios, at locations coincident with calcification, that correlated with increased collagen disorganization and positive expression of osteogenic markers. Additionally, locations with lower TPEF autofluorescence ratios at 4 and 16 weeks exhibited increased calcification at later 28-week timepoints. This study suggests the potential of TPEF autofluorescence metrics to serve as a label-free tool for early detection and monitoring of CAVD pathophysiology.
Sections du résumé
BACKGROUND
Calcific aortic valve disease (CAVD) pathophysiology is a complex, multistage process, usually diagnosed at advanced stages after significant anatomical and hemodynamic changes in the valve. Early detection of disease progression is thus pivotal in the development of prevention and mitigation strategies. In this study, we developed a diet-based, non-genetically modified mouse model for early CAVD progression, and explored the utility of two-photon excited fluorescence (TPEF) microscopy for early detection of CAVD progression. TPEF imaging provides label-free, non-invasive, quantitative metrics with the potential to correlate with multiple stages of CAVD pathophysiology including calcium deposition, collagen remodeling and osteogenic differentiation.
METHODS
Twenty-week old C57BL/6J mice were fed either a control or pro-calcific diet for 16 weeks and monitored via echocardiography, histology, immunohistochemistry, and quantitative polarized light imaging. Additionally, TPEF imaging was used to quantify tissue autofluorescence (A) at 755 nm, 810 nm and 860 nm excitation, to calculate TPEF 755-860 ratio (A
RESULTS
Pro-calcific mice showed evidence of lipid deposition at 4 weeks and calcification at 16 weeks at the valve commissures. The valves of pro-calcific mice also showed positive expression for markers of osteogenic differentiation, myofibroblast activation, proliferation, inflammatory cytokines and collagen remodeling. Pro-calcific mice exhibited lower TPEF autofluorescence ratios, at locations coincident with calcification, that correlated with increased collagen disorganization and positive expression of osteogenic markers. Additionally, locations with lower TPEF autofluorescence ratios at 4 and 16 weeks exhibited increased calcification at later 28-week timepoints.
CONCLUSIONS
This study suggests the potential of TPEF autofluorescence metrics to serve as a label-free tool for early detection and monitoring of CAVD pathophysiology.
Identifiants
pubmed: 33308143
doi: 10.1186/s12872-020-01776-8
pii: 10.1186/s12872-020-01776-8
pmc: PMC7731510
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
521Subventions
Organisme : NIH HHS
ID : R00EB017723
Pays : United States
Organisme : National Science Foundation
ID : CMMI-1452943
Pays : International
Organisme : American Heart Association
ID : 19PRE34370061
Pays : International
Organisme : NIH HHS
ID : 1R01HL13366701A1
Pays : United States
Organisme : NIBIB NIH HHS
ID : R00 EB017723
Pays : United States
Organisme : American Heart Association
ID : 18AIREA33900098
Pays : International
Organisme : NIH HHS
ID : 1R01HL14471401A1
Pays : United States
Organisme : NIH HHS
ID : R01AG056560
Pays : United States
Organisme : National Science Foundation
ID : CBET-1846853
Pays : International
Organisme : NIH HHS
ID : 1R01HL14032501A1
Pays : United States
Organisme : NIH HHS
ID : 1R01HL13514501A1
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056560
Pays : United States
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