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

作者：Borthwick Faye; Warnakula Samantha; Mangat Rabban; Uwiera Richard R; Russell James C; Kelly Sandra E; Lee Candace Y; Hryshko Larry; Mamo John C L; Rye Kerry Anne; Lopaschuk Gary D; Proctor Spencer D^*

来源：Atherosclerosis, 2012, 222(2): 402-408.

DOI：10.1016/j.atherosclerosis.2012.03.006

• Apolipoprotein-A1
• High-density lipoprotein
• Insulin resistance
• Arterial cholesterol
• Cardiac dysfunction

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. %26lt;br%26gt;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 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 %26lt; 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 %26lt; 0.01) ex vivo in IR and male Wistar rats and reduced (41%; *p %26lt; 0.05) the frequency of early-stage myocardial lesions in IR rats. %26lt;br%26gt;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.

• 出版日期2012-6