Thromboxane A synthase enhances blood flow recovery from hindlimb ischemia

Hideki Amano, Masaki Nakamura, Yoshiya Ito, Hiroki Kakutani, Koji Eshima, Hidero Kitasato, Shuh Narumiya, Masataka Majima

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    Abstract

    Background Thromboxane A synthase (TXAS) is the enzyme that converts the arachidonic acid derivative prostaglandin H2 to thromboxane A2 (TXA2). TXA2 induces platelet aggregation, vasoconstriction, and proliferation. TXAS and TXA2 receptors or thromboxane prostanoid (TP) receptors are elevated in numerous cardiovascular and inflammatory diseases. Platelets contain numerous angiogenesis stimulating factors. However, the involvement of TXAS on recovery from an ischemic condition is not well understood. We hypothesized that the TXAS-TXA2-TP receptor axis would induce blood flow recovery by platelet activation. Material and methods The model of hindlimb ischemia was made by the right femoral artery ligation. The blood flow was estimated by laser Doppler images. Angiogenesis was estimated by the plasma level of the vascular endothelial growth factor and the stromal cell-derived factor-1 and by immunofluorescence analysis against CD31 and P-selectin glycoprotein ligand-1 (PSGL-1). Results In wild-type mice, blood flow recovery was enhanced by treatment with murine TXAS-overexpressing fibroblasts (C57-mTXAS) compared with empty vector- (EV) treated fibroblasts (C57-EV). Compared with C57-EV-treated mice, activated platelets (P-selectin+ platelets) and plasma levels of vascular endothelial growth factor and stromal cell-derived factor-1 were increased in C57-mTXAS-treated mice. The enhanced-blood flow recovery by C57-mTXAS treatment was suppressed in the TP knockout mice (TP-/-). The expression of PSGL-1 in endothelial cells around the ischemic area was enhanced by C57-mTXAS treatment in wild-type but not in TP-/-. Conclusions These results indicated that local administration of C57-mTXAS-induced angiogenesis by activated platelets that bind to PSGL-1 on ischemic endothelial cells.

    Original languageEnglish (US)
    Pages (from-to)153-163
    Number of pages11
    JournalJournal of Surgical Research
    Volume204
    Issue number1
    DOIs
    StatePublished - Jul 1 2016

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    Keywords

    • Angiogenesis
    • P-selectin ligand protein-1
    • Platelet activation
    • Thromboxane A synthase
    • Thromboxane A2

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Amano, H., Nakamura, M., Ito, Y., Kakutani, H., Eshima, K., Kitasato, H., Narumiya, S., & Majima, M. (2016). Thromboxane A synthase enhances blood flow recovery from hindlimb ischemia. Journal of Surgical Research, 204(1), 153-163. https://doi.org/10.1016/j.jss.2016.04.011