Label-free optical biomarkers detect early calcific aortic valve disease in a wild-type mouse model.

摘要: 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 progression thus pivotal development prevention mitigation strategies. In this study, we developed diet-based, non-genetically modified mouse model for early CAVD progression, explored utility two-photon excited fluorescence (TPEF) microscopy progression. TPEF imaging provides label-free, non-invasive, quantitative metrics with potential to correlate multiple including calcium deposition, collagen remodeling osteogenic differentiation. Twenty-week old C57BL/6J mice were fed either control or pro-calcific diet 16 weeks monitored via echocardiography, histology, immunohistochemistry, polarized light imaging. Additionally, was used quantify tissue autofluorescence (A) 755 nm, 810 nm 860 nm excitation, calculate 755–860 ratio (A860/525/(A755/460 + A860/525)) Collagen-Calcium (A810/525/(A810/460 + A810/525)) murine valves. separate experiment, animals above diets till 28 weeks assess later-stage calcification. Pro-calcific showed evidence lipid deposition 4 weeks calcification commissures. The valves also positive expression markers differentiation, myofibroblast activation, proliferation, inflammatory cytokines remodeling. exhibited lower ratios, locations coincident calcification, that correlated increased disorganization markers. ratios 4 later 28-week timepoints. This study suggests serve as label-free tool monitoring pathophysiology.