title: ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Metabolic and Cardiovascular Diseases Laboratory, Molecular and Cell Biology of Lipids Group, Alberta Diabetes and Mazankowski Heart Institutes, Edmonton, Alberta, Canada.
authors.forename: Faye
authors.initials: F
authors.lastname: Borthwick
authors.forename: Samantha
authors.initials: S
authors.lastname: Warnakula
authors.forename: Rabban
authors.initials: R
authors.lastname: Mangat
authors.forename: Richard R
authors.initials: RR
authors.lastname: Uwiera
authors.forename: James C
authors.initials: JC
authors.lastname: Russell
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Kelly
authors.forename: Candace Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Larry
authors.initials: L
authors.lastname: Hryshko
authors.forename: John C L
authors.initials: JC
authors.lastname: Mamo
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Proctor
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D006801:Humans; D007263:Infusions, Parenteral; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000008:administration & dosage*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000150:complications; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol