ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance
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/o...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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Elsevier Ireland
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/28338 |
| _version_ | 1848752509449928704 |
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| author | Borthwick, F. Warnakula, S. Mangat, R. Uwiera, R. Russell, J. Kelly, S. Lee, C. Hryshko, L. Mamo, John Rye, K. Lopaschuk, G. Proctor, S. |
| author_facet | Borthwick, F. Warnakula, S. Mangat, R. Uwiera, R. Russell, J. Kelly, S. Lee, C. Hryshko, L. Mamo, John Rye, K. Lopaschuk, G. Proctor, S. |
| author_sort | Borthwick, F. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T08:09:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-28338 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:09:45Z |
| publishDate | 2012 |
| publisher | Elsevier Ireland |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-283382017-09-13T15:53:33Z ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance Borthwick, F. Warnakula, S. Mangat, R. Uwiera, R. Russell, J. Kelly, S. Lee, C. Hryshko, L. Mamo, John Rye, K. Lopaschuk, G. Proctor, S. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/28338 10.1016/j.atherosclerosis.2012.03.006 Elsevier Ireland restricted |
| spellingShingle | Borthwick, F. Warnakula, S. Mangat, R. Uwiera, R. Russell, J. Kelly, S. Lee, C. Hryshko, L. Mamo, John Rye, K. Lopaschuk, G. Proctor, S. ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| title | ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| title_full | ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| title_fullStr | ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| title_full_unstemmed | ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| title_short | ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| title_sort | apoa-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance |
| url | http://hdl.handle.net/20.500.11937/28338 |