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    Exendin-4 protected against critical limb ischemia in obese mice.

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    URI
    http://hdl.handle.net/11287/610877
    Author
    Sheu, J-J
    Chang, M-W
    Wallace, Christopher G
    Chiang, H-J
    Sung, P-H
    Tsai, T-H
    Chung, S-Y
    Chen, Y-L
    Chua, S
    Chang, H-W
    Sun, C-K
    Lee, F-Y
    Yip, H-K
    Date
    2015-03-15
    Journal
    American journal of translational research
    Type
    Journal Article
    Publisher
    e-Century Publishing
    Rights
    Archived with thanks to American journal of translational research
    Metadata
    Show full item record
    Abstract
    This study tested the hypothesis that exendin-4 protects against critical limb ischemia (CLI) in obese mice undergoing hypoxic stress (H). B6 mice were categorized into aged-matched control (C)-H (group 1-A), obesity (induced by high-fat diet) (O)-H (group 1-B), C-H-CLI (group 2-A), O-H-CLI (group 2-B), C-H-CLI-exendin-4 (group 3-A) and O-H-CLI-exendin-4 (group 3-B). Animals were sacrificed by day 14 after CLI procedure. By day 14, laser Doppler results showed that blood flow in CLI area was higher in group 3-A than group 2-A, higher in group 3-B than group 2-B, highest in groups 1-A and 1-B, higher in group 2-A than in group 2-B, and higher in group 3-A than in group 3-B (all p<0.001), but not significantly different between groups 1-A and 1-B. Furthermore, circulating numbers of endothelial progenitor cells (EPCs) (c-kit/CD31+, Sca-1/KDR+) showed an identical pattern of blood flow in CLI area among groups 2-A, 2-B, 3-A and 3-B, except that these biomarkers were lowest in groups 1-A and 1-B (all p<0.001). Protein and cellular levels of angiogenesis factors (VEGF, CXCR4, SDF-1α) exhibited an identical pattern of circulating EPC numbers among all groups (all p<0.001). Protein levels of apoptotic (cytosolic cytochrome-C, mitochondrial Bax, cleaved caspase 3 and PARP) and fibrotic (Samd 3, TGF-β) biomarkers showed an opposite pattern of blood flow in CLI area among groups 2-A, 2-B, 3-A and 3-B, but were lowest in groups 1-A and 1-B (all p<0.001). This finding suggests exendin-4 protected against CLI in obese mice undergoing hypoxic stress mainly through enhancing angiogenesis and inhibiting apoptosis.
    Citation
    Exendin-4 protected against critical limb ischemia in obese mice. 2015, 7 (3):445-59 Am J Transl Res
    Publisher URL
    http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26045886/
    Note
    The full-text of this article is free via PubMed Central. Click on the 'Additional Link' above to access the full-text.
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    • Plastic & Reconstructive Surgery

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