title: Quantification of aortic and cutaneous elastin and collagen morphology in Marfan syndrome by multiphoton microscopy.
abstract: In a mouse model of Marfan syndrome, conventional Verhoeff-Van Gieson staining displays severe fragmentation, disorganization and loss of the aortic elastic fiber integrity. However, this method involves chemical fixatives and staining, which may alter the native morphology of elastin and collagen. Thus far, quantitative analysis of fiber damage in aorta and skin in Marfan syndrome has not yet been explored. In this study, we have used an advanced noninvasive and label-free imaging technique, multiphoton microscopy to quantify fiber fragmentation, disorganization, and total volumetric density of aortic and cutaneous elastin and collagen in a mouse model of Marfan syndrome. Aorta and skin samples were harvested from Marfan and control mice aged 3-, 6- and 9-month. Elastin and collagen were identified based on two-photon excitation fluorescence and second-harmonic-generation signals, respectively, without exogenous label. Measurement of fiber length indicated significant fragmentation in Marfan vs. control. Fast Fourier transform algorithm analysis demonstrated markedly lower fiber organization in Marfan mice. Significantly reduced volumetric density of elastin and collagen and thinner skin dermis were observed in Marfan mice. Cutaneous content of elastic fibers and thickness of dermis in 3-month Marfan resembled those in the oldest control mice. Our findings of early signs of fiber degradation and thinning of skin dermis support the potential development of a novel non-invasive approach for early diagnosis of Marfan syndrome.
authors.affiliation: Child & Family Research Institute, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Cui
authors.affiliation: Child & Family Research Institute, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Arash Y
authors.initials: AY
authors.lastname: Tehrani
authors.affiliation: Child & Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Jett
authors.affiliation: Institute for HEART+LUNG Health, Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bernatchez
authors.affiliation: Child & Family Research Institute, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
authors.affiliation: Child & Family Research Institute, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada; Department of Biomedical Sciences, College of Health Sciences, Midwestern University, Glendale, AZ, USA. Electronic address: mesfan@midwestern.edu.
authors.forename: Mitra
authors.initials: M
authors.lastname: Esfandiarei
mesh_terms: D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004549:Elastin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008382:Marfan Syndrome / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D008958:Models, Molecular; D012867:Skin / Q000378:metabolism*
chemical_list: D003094:Collagen; D004549:Elastin
keywords: Aortic aneurysm; Elastin fragmentation; Fast Fourier analysis; Marfan syndrome; Multiphoton microscopy