Blocking thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia

Jeff S. Isenberg, Fuminori Hyodo, Loretta K. Pappan, Mones Abu-Asab, Maria Tsokos, Murali C. Krishna, William A. Frazier, David D. Roberts

    研究成果: ジャーナルへの寄稿学術誌査読

    66 被引用数 (Scopus)

    抄録

    OBJECTIVE - Decreased blood flow secondary to peripheral vascular disease underlies a significant number of chronic diseases that account for the majority of morbidity and mortality among the elderly. Blood vessel diameter and blood flow are limited by the matricellular protein thrombospondin-1 (TSP1) through its ability to block responses to the endogenous vasodilator nitric oxide (NO). In this study we investigate the role TSP1 plays in regulating blood flow in the presence of advanced age and atherosclerotic vascular disease. METHODS AND RESULTS - Mice lacking TSP1 or CD47 show minimal loss of their resistance to ischemic injury with age and increased preservation of tissue perfusion immediately after injury. Treatment of WT and apolipoprotein E-null mice using therapeutic agents that decrease CD47 or enhance NO levels reverses the deleterious effects of age- and diet-induced vasculopathy and results in significantly increased tissue survival in models of ischemia. CONCLUSION - With increasing age and diet-induced atherosclerotic vascular disease, TSP1 and its receptor CD47 become more limiting for blood flow and tissue survival after ischemic injury. Drugs that limit TSP1/CD47 regulation of blood flow could improve outcomes from surgical interventions in the elderly and ameliorate vascular complications attendant to aging.

    本文言語英語
    ページ(範囲)2582-2588
    ページ数7
    ジャーナルArteriosclerosis, thrombosis, and vascular biology
    27
    12
    DOI
    出版ステータス出版済み - 12月 2007

    !!!All Science Journal Classification (ASJC) codes

    • 循環器および心血管医学

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