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    ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance

    Access Status
    Fulltext not available
    Authors
    Borthwick, F.
    Warnakula, S.
    Mangat, R.
    Uwiera, R.
    Russell, J.
    Kelly, S.
    Lee, C.
    Hryshko, L.
    Mamo, John
    Rye, K.
    Lopaschuk, G.
    Proctor, S.
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Borthwick, Faye and Warnakula, Samantha and Mangat, Rabban and Uwiera, Richard and Russell, James and Kelly, Sandra and Lee, Candace and Hryshko, Larry and Mamo, John and Rye, Kerry-Anne and Lopaschuk, Gary and Proctor, Spencer. 2012. ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance. Atherosclerosis. 222: pp. 402-208.
    Source Title
    Atherosclerosis
    DOI
    10.1016/j.atherosclerosis.2012.03.006
    ISSN
    00219150
    URI
    http://hdl.handle.net/20.500.11937/28338
    Collection
    • Curtin Research Publications
    Abstract

    OBJECTIVE Low plasma high-density lipoprotein cholesterol (HDL-C) concentration is associated with the metabolic syndrome (MetS) and increased prevalence of cardiovascular disease (CVD). Animal and human studies report infusion of apolipoprotein A-1 (apoA-1) can reduce endothelial dysfunction, and/or induce regression of atherosclerosis. However, the direct mechanisms underlying the vascular benefits of either apoA-1 or HDL-C remain unclear. In this study, we assessed the ability of reconstituted HDL (rHDL) to improve vascular complications of MetS, including left ventricular (LV)-hypertrophy, arterial cholesterol deposition and myocardial lesion development. METHODS AND RESULTS Obese insulin resistant (IR) JCR:LA-cp rats were infused with rHDL (0.4 mg/kg) over 3 days before assessing cardiac function (Echocardiography) at days 7 and 50 post-infusion, as well as haematoxylin and eosin staining of myocardial lesions at day 50. Acute ex vivo arterial cholesterol deposition was assessed with acute infusion of rHDL ex-vivo. Infusion of rHDL partially corrected abnormal diastolic compliance (18%; *p < 0.05) and improved parameters of cardiac function in IR rats. Further, acute rHDL infusion in carotid vessels reduced remnant lipoprotein associated-cholesterol deposition (30–86%; **p < 0.01) ex vivo in IR and male Wistar rats and reduced (41%; *p < 0.05) the frequency of early-stage myocardial lesions in IR rats. CONCLUSION Short-term infusion of rHDL may beneficially reduce chronic vascular sequelae of MetS, including temporary improvement in LV-dysfunction, acute reduction of acute arterial cholesterol deposition and the development of early-stage myocardial lesions in the JCR:LA-cp rat.

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