ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance
Autor: | Faye Borthwick, Sandra E. Kelly, Kerry-Anne Rye, Rabban Mangat, Samantha Warnakula, Richard R. E. Uwiera, Larry Hryshko, John C.L. Mamo, Spencer D. Proctor, James C. Russell, Candace Y. Lee, Gary D. Lopaschuk |
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Rok vydání: | 2011 |
Předmět: |
Cardiac function curve
Carotid Artery Diseases Male medicine.medical_specialty Time Factors Apolipoprotein B Ventricular Function Left chemistry.chemical_compound Ventricular Dysfunction Left Insulin resistance High-density lipoprotein Internal medicine medicine Animals Humans Infusions Parenteral Obesity Endothelial dysfunction Rats Wistar Metabolic Syndrome biology Apolipoprotein A-I business.industry Cholesterol Myocardium medicine.disease Echocardiography Doppler Rats Disease Models Animal Endocrinology Carotid Arteries chemistry biology.protein lipids (amino acids peptides and proteins) Apolipoprotein A1 Metabolic syndrome Insulin Resistance Cardiology and Cardiovascular Medicine business Lipoproteins HDL |
Zdroj: | Atherosclerosis. 222(2) |
ISSN: | 1879-1484 |
Popis: | 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.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%; *p0.05) and improved parameters of cardiac function in IR rats. Further, acute rHDL infusion in carotid vessels reduced remnant lipoprotein associated-cholesterol deposition (30-86%; **p0.01) ex vivo in IR and male Wistar rats and reduced (41%; *p0.05) the frequency of early-stage myocardial lesions in IR rats.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. |
Databáze: | OpenAIRE |
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