Temporal exposure of cryptic collagen epitopes within ischemic muscle during hindlimb reperfusion

Paul J. Gagne, Nikita Tihonov, Xialou Li, Joseph Glaser, Jhenrong Qiao, Michael Silberstein, Herman Yee, Elizabeth Gagne, Peter Brooks

    Research output: Contribution to journalArticle

    23 Scopus citations

    Abstract

    Chronic limb-threatening ischemia is a devastating disease with limited surgical options. However, inducing controlled angiogenesis and enhancing reperfusion holds therapeutic promise. To gain a better understanding of the mechanisms that contribute to limb reperfusion, we examined the temporal biochemical and structural changes occurring within the extracellular matrix of ischemic skeletal muscle. Both the latent and active forms of MMP-2 and -9 significantly increased during the active phase of limb reperfusion. Moreover, small but significant alterations in tissue inhibitors of metalloproteinase levels also occurred during a similar time course, consistent with a net increase in extracellular matrix remodeling. This temporal increase in MMP activity coincided with enhanced exposure of the unique HU177 cryptic collagen epitope. Although the HUIV26 cryptic collagen epitope has been implicated in angiogenesis, little is known concerning such epitopes within ischemic muscle tissue. Here, we provide the first evidence that a functionally distinct cryptic collagen epitope (HU177) is temporally exposed in ischemic muscle tissue during the active phase of reperfusion. Interestingly, the exposure of the HU177 epitope was greatly diminished in MMP-9 null mice, corresponding with significantly reduced limb reperfusion. Therefore, the regulated exposure of a unique cryptic collagen epitope within ischemic muscle suggests an important role for collagen remodeling during the active phase of ischemic limb reperfusion.

    Original languageEnglish (US)
    Pages (from-to)1349-1359
    Number of pages11
    JournalAmerican Journal of Pathology
    Volume167
    Issue number5
    DOIs
    StatePublished - Nov 2005

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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    Gagne, P. J., Tihonov, N., Li, X., Glaser, J., Qiao, J., Silberstein, M., Yee, H., Gagne, E., & Brooks, P. (2005). Temporal exposure of cryptic collagen epitopes within ischemic muscle during hindlimb reperfusion. American Journal of Pathology, 167(5), 1349-1359. https://doi.org/10.1016/S0002-9440(10)61222-9