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ApoA-1 Infusion Reduces Arterial Cholesterol and Myocardial Lesions in a Rat Model of Cardiac Dysfunction and Insulin Resistance

ApoA-1 Infusion Reduces Arterial Cholesterol and Myocardial Lesions in a Rat Model of Cardiac Dysfunction and Insulin Resistance

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

Atherosclerosis. 2012 Jun;222(2):402-8.

PMID: 22483015

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4247084	ApoA-1 from rat			Price

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