Molecular Imaging of VWF (von Willebrand Factor) and Platelet Adhesion in Postischemic Impaired Microvascular Reflow

Koya Ozawa, William Packwood, Oleg Varlamov, Yue Qi, Aris Xie, Melinda D. Wu, Zaverio Ruggeri, Jose A. López, Jonathan R. Lindner

    Research output: Contribution to journalArticle

    5 Scopus citations

    Abstract

    BACKGROUND: Complete mechanistic understanding of impaired microvascular reflow after myocardial infarction will likely lead to new therapies for reducing infarct size. Myocardial contrast echocardiography perfusion imaging and molecular imaging were used to evaluate the contribution of microvascular endothelial-associated VWF (von Willebrand factor) and platelet adhesion to microvascular no-reflow. METHODS AND RESULTS: Myocardial infarction was produced by transient LAD ligation in WT (wild type) mice, WT mice treated with the VWF proteolytic enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and ADAMTS13-deficient (ADAMTS13-/-) mice. Myocardial contrast echocardiography perfusion imaging and molecular imaging of VWF and platelet GP (glycoprotein) Ibα were performed 30 minutes after ischemia-reperfusion. Infarct size was measured at 3 days. Mortality during ischemia-reperfusion incrementally increased in WT+ADAMTS13, WT, and ADAMTS13-/- mice (14%, 43%, and 63%, respectively; P<0.05). For WT mice, molecular imaging signal for platelets and VWF in the postischemic risk area was 4- to 5-fold higher ( P<0.05) compared with both the remote nonischemic regions or to sham-treated mice. Signal enhancement in the risk area was completely abolished by ADAMTS13 treatment for both platelets (12.8±3.3 versus -1.0±4.4 IU; P<0.05) and VWF (13.9±4.0 versus -1.0±3.0 IU; P<0.05). ADAMTS13-/- compared with WT mice had 2- to 3-fold higher risk area signal for platelets (33.1±8.5 IU) and VWF (30.9±1.9 IU). Microvascular reflow in the risk area incrementally decreased for WT+ADAMTS13, WT, and ADAMTS13-/- mice ( P<0.05), whereas infarct size incrementally increased ( P<0.05). CONCLUSIONS: Mechanistic information on microvascular no-reflow is possible by combining perfusion and molecular imaging. In reperfused myocardial infarction, excess endothelial-associated VWF and secondary platelet adhesion in the risk area microcirculation contribute to impaired reflow and are modifiable.

    Original languageEnglish (US)
    Pages (from-to)e007913
    JournalCirculation. Cardiovascular imaging
    Volume11
    Issue number11
    DOIs
    StatePublished - Nov 1 2018

    Keywords

    • blood platelet
    • echocardiography
    • molecular imaging
    • myocardial infarction
    • myocardial ischemia

    ASJC Scopus subject areas

    • Radiology Nuclear Medicine and imaging
    • Cardiology and Cardiovascular Medicine

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