In vivo noninvasive measurement of skin autofluorescence biomarkers relate to cardiovascular disease in mice

N. Akbar, S. Sokolovski, A. Dunaev, J. J. F. Belch, E. Rafailov, F. Khan (Lead / Corresponding author)

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    Abstract

    Background and objective
    The formation of reactive oxygen species (ROS) is associated with cardiovascular disease (CVD). High dietary cholesterol can significantly alter the delicate balance between pro-oxidation and antioxidant defences leading to reactive oxygen species formation in the vasculature, without significant structural changes in tissue composition. We aimed to establish a methodology for the noninvasive assessment of skin fluorescent biomarkers in mice.

    Materials and methods
    C57/black/6 wild-type (WT; n = 25) male mice were subdivided to receive normal rodent chow (n = 11) or a high cholesterol diet (2% cholesterol; n = 14) for 20 weeks. Skin autofluorescence measurements were made on the backs of anaesthetized (1.5–2% isoflurane in oxygen) mice. A laser probe was used to make simultaneous measurements of: collagen, elastin, nicotinamide adenine dinucleotide, pyridoxine, flavins, lipofuscin and ß-carotene. Results are expressed as group mean in arbitrary units (AU) ± standard error (SE). Hearts were excised and weighed (mg); cardiac hypertrophy was measured by ratio [heart weight (mg)/bodyweight (g) ± SE]. Student's t-test was used for statistical significance analysis (p = 0.05).

    Results
    There were no significant differences between cholesterol- and chow-fed animals for collagen (34 ± 5AU vs. chow 34 ± 4 AU, p = 0.51) and elastin (66 ± 6 AU vs. chow 82 ± 7 AU, p = 0.11). Significant differences were evident for nicotinamide adenine dinucleotide (92 ± 7 AU vs. chow 118 ± 7 AU, p = 0.01), pyridoxine (56 ± 4 AU vs. chow 73 ± 4 AU, p = 0.01), flavins (44 ± 3 AU vs. chow 57 ± 4 AU, p = 0.01), lipofuscin (35 ± 3 AU vs. chow 46 ± 3 AU, p = 0.01) and ß-carotene (19 ± 2 AU vs. chow 25 ± 2 AU, p = 0.01). Cholesterol-fed animals had significantly heavier hearts (7 ± 0.3 ratio vs. chow 5 ± 0.1 ratio, p = 0.001).

    Conclusion
    Cholesterol feeding induced cardiovascular disease as noted by cardiac hypertrophy in wild-type mice. A reduction was observed in pyridoxine, nicotinamide adenine dinucleotide, flavins, lipofuscin and ß-carotene, which are established risk factors for cardiovascular disease. We report no significant changes in structural proteins collagen and elastin, suggesting no generalized tissue restructuring, which might otherwise explain the observed pathological differences.
    Original languageEnglish
    Number of pages7
    JournalJournal of Microscopy
    Early online date8 May 2014
    DOIs
    Publication statusPublished - 2014

    Fingerprint

    Flavins
    Lipofuscin
    Pyridoxine
    Elastin
    Cardiovascular Diseases
    Carotenoids
    Biomarkers
    Cholesterol
    NAD
    Skin
    Collagen
    Cardiomegaly
    Reactive Oxygen Species
    Dietary Cholesterol
    Isoflurane
    Rodentia
    Lasers
    Antioxidants
    Students
    Oxygen

    Cite this

    @article{cbaceafe2dd14093b2552c3cc3206dbd,
    title = "In vivo noninvasive measurement of skin autofluorescence biomarkers relate to cardiovascular disease in mice",
    abstract = "Background and objectiveThe formation of reactive oxygen species (ROS) is associated with cardiovascular disease (CVD). High dietary cholesterol can significantly alter the delicate balance between pro-oxidation and antioxidant defences leading to reactive oxygen species formation in the vasculature, without significant structural changes in tissue composition. We aimed to establish a methodology for the noninvasive assessment of skin fluorescent biomarkers in mice.Materials and methodsC57/black/6 wild-type (WT; n = 25) male mice were subdivided to receive normal rodent chow (n = 11) or a high cholesterol diet (2{\%} cholesterol; n = 14) for 20 weeks. Skin autofluorescence measurements were made on the backs of anaesthetized (1.5–2{\%} isoflurane in oxygen) mice. A laser probe was used to make simultaneous measurements of: collagen, elastin, nicotinamide adenine dinucleotide, pyridoxine, flavins, lipofuscin and {\ss}-carotene. Results are expressed as group mean in arbitrary units (AU) ± standard error (SE). Hearts were excised and weighed (mg); cardiac hypertrophy was measured by ratio [heart weight (mg)/bodyweight (g) ± SE]. Student's t-test was used for statistical significance analysis (p = 0.05).ResultsThere were no significant differences between cholesterol- and chow-fed animals for collagen (34 ± 5AU vs. chow 34 ± 4 AU, p = 0.51) and elastin (66 ± 6 AU vs. chow 82 ± 7 AU, p = 0.11). Significant differences were evident for nicotinamide adenine dinucleotide (92 ± 7 AU vs. chow 118 ± 7 AU, p = 0.01), pyridoxine (56 ± 4 AU vs. chow 73 ± 4 AU, p = 0.01), flavins (44 ± 3 AU vs. chow 57 ± 4 AU, p = 0.01), lipofuscin (35 ± 3 AU vs. chow 46 ± 3 AU, p = 0.01) and {\ss}-carotene (19 ± 2 AU vs. chow 25 ± 2 AU, p = 0.01). Cholesterol-fed animals had significantly heavier hearts (7 ± 0.3 ratio vs. chow 5 ± 0.1 ratio, p = 0.001).ConclusionCholesterol feeding induced cardiovascular disease as noted by cardiac hypertrophy in wild-type mice. A reduction was observed in pyridoxine, nicotinamide adenine dinucleotide, flavins, lipofuscin and {\ss}-carotene, which are established risk factors for cardiovascular disease. We report no significant changes in structural proteins collagen and elastin, suggesting no generalized tissue restructuring, which might otherwise explain the observed pathological differences.",
    author = "N. Akbar and S. Sokolovski and A. Dunaev and Belch, {J. J. F.} and E. Rafailov and F. Khan",
    note = "{\circledC} 2014 The Authors Journal of Microscopy {\circledC} 2014 Royal Microscopical Society.",
    year = "2014",
    doi = "10.1111/jmi.12135",
    language = "English",
    journal = "Journal of Microscopy",
    issn = "0022-2720",
    publisher = "Wiley",

    }

    TY - JOUR

    T1 - In vivo noninvasive measurement of skin autofluorescence biomarkers relate to cardiovascular disease in mice

    AU - Akbar, N.

    AU - Sokolovski, S.

    AU - Dunaev, A.

    AU - Belch, J. J. F.

    AU - Rafailov, E.

    AU - Khan, F.

    N1 - © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

    PY - 2014

    Y1 - 2014

    N2 - Background and objectiveThe formation of reactive oxygen species (ROS) is associated with cardiovascular disease (CVD). High dietary cholesterol can significantly alter the delicate balance between pro-oxidation and antioxidant defences leading to reactive oxygen species formation in the vasculature, without significant structural changes in tissue composition. We aimed to establish a methodology for the noninvasive assessment of skin fluorescent biomarkers in mice.Materials and methodsC57/black/6 wild-type (WT; n = 25) male mice were subdivided to receive normal rodent chow (n = 11) or a high cholesterol diet (2% cholesterol; n = 14) for 20 weeks. Skin autofluorescence measurements were made on the backs of anaesthetized (1.5–2% isoflurane in oxygen) mice. A laser probe was used to make simultaneous measurements of: collagen, elastin, nicotinamide adenine dinucleotide, pyridoxine, flavins, lipofuscin and ß-carotene. Results are expressed as group mean in arbitrary units (AU) ± standard error (SE). Hearts were excised and weighed (mg); cardiac hypertrophy was measured by ratio [heart weight (mg)/bodyweight (g) ± SE]. Student's t-test was used for statistical significance analysis (p = 0.05).ResultsThere were no significant differences between cholesterol- and chow-fed animals for collagen (34 ± 5AU vs. chow 34 ± 4 AU, p = 0.51) and elastin (66 ± 6 AU vs. chow 82 ± 7 AU, p = 0.11). Significant differences were evident for nicotinamide adenine dinucleotide (92 ± 7 AU vs. chow 118 ± 7 AU, p = 0.01), pyridoxine (56 ± 4 AU vs. chow 73 ± 4 AU, p = 0.01), flavins (44 ± 3 AU vs. chow 57 ± 4 AU, p = 0.01), lipofuscin (35 ± 3 AU vs. chow 46 ± 3 AU, p = 0.01) and ß-carotene (19 ± 2 AU vs. chow 25 ± 2 AU, p = 0.01). Cholesterol-fed animals had significantly heavier hearts (7 ± 0.3 ratio vs. chow 5 ± 0.1 ratio, p = 0.001).ConclusionCholesterol feeding induced cardiovascular disease as noted by cardiac hypertrophy in wild-type mice. A reduction was observed in pyridoxine, nicotinamide adenine dinucleotide, flavins, lipofuscin and ß-carotene, which are established risk factors for cardiovascular disease. We report no significant changes in structural proteins collagen and elastin, suggesting no generalized tissue restructuring, which might otherwise explain the observed pathological differences.

    AB - Background and objectiveThe formation of reactive oxygen species (ROS) is associated with cardiovascular disease (CVD). High dietary cholesterol can significantly alter the delicate balance between pro-oxidation and antioxidant defences leading to reactive oxygen species formation in the vasculature, without significant structural changes in tissue composition. We aimed to establish a methodology for the noninvasive assessment of skin fluorescent biomarkers in mice.Materials and methodsC57/black/6 wild-type (WT; n = 25) male mice were subdivided to receive normal rodent chow (n = 11) or a high cholesterol diet (2% cholesterol; n = 14) for 20 weeks. Skin autofluorescence measurements were made on the backs of anaesthetized (1.5–2% isoflurane in oxygen) mice. A laser probe was used to make simultaneous measurements of: collagen, elastin, nicotinamide adenine dinucleotide, pyridoxine, flavins, lipofuscin and ß-carotene. Results are expressed as group mean in arbitrary units (AU) ± standard error (SE). Hearts were excised and weighed (mg); cardiac hypertrophy was measured by ratio [heart weight (mg)/bodyweight (g) ± SE]. Student's t-test was used for statistical significance analysis (p = 0.05).ResultsThere were no significant differences between cholesterol- and chow-fed animals for collagen (34 ± 5AU vs. chow 34 ± 4 AU, p = 0.51) and elastin (66 ± 6 AU vs. chow 82 ± 7 AU, p = 0.11). Significant differences were evident for nicotinamide adenine dinucleotide (92 ± 7 AU vs. chow 118 ± 7 AU, p = 0.01), pyridoxine (56 ± 4 AU vs. chow 73 ± 4 AU, p = 0.01), flavins (44 ± 3 AU vs. chow 57 ± 4 AU, p = 0.01), lipofuscin (35 ± 3 AU vs. chow 46 ± 3 AU, p = 0.01) and ß-carotene (19 ± 2 AU vs. chow 25 ± 2 AU, p = 0.01). Cholesterol-fed animals had significantly heavier hearts (7 ± 0.3 ratio vs. chow 5 ± 0.1 ratio, p = 0.001).ConclusionCholesterol feeding induced cardiovascular disease as noted by cardiac hypertrophy in wild-type mice. A reduction was observed in pyridoxine, nicotinamide adenine dinucleotide, flavins, lipofuscin and ß-carotene, which are established risk factors for cardiovascular disease. We report no significant changes in structural proteins collagen and elastin, suggesting no generalized tissue restructuring, which might otherwise explain the observed pathological differences.

    U2 - 10.1111/jmi.12135

    DO - 10.1111/jmi.12135

    M3 - Article

    JO - Journal of Microscopy

    JF - Journal of Microscopy

    SN - 0022-2720

    ER -