ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline CharacteristicsLonn, E.; Bosch, J.; Pogue, J.; Avezum, A.; Chazova, I.; Dans, A.; Diaz, R.; Fodor, G.; Held, C.; Jansky, P.; Keltai, M.; Keltai, K.; Kunti, K.; Kim, J.; Leiter, L.; Lewis, B.; Liu, L.; Lopez-Jaramillo, P.; Pais, P.; Parkhomenko, A.; Peters, R.; Piegas, L.; Reid, Christopher; Sliwa, K.; Toff, W.; Varigos, J.; Xavier, D.; Yusoff, K.; Zhu, J.; Dagenais, G.; Yusuf, S.; HOPE-3 Investigators (2015)BACKGROUND: Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. ...
Outcomes after percutaneous coronary intervention of ostial lesions in the era of drug-eluting stentsFreeman, M.; Clark, D.; Andrianopoulos, N.; Duffy, S.; Lim, H.; Brennan, A.; Charter, K.; Shaw, J.; Horrigan, M.; Ajani, A.; Sebastian, M.; Reid, Christopher; Farouque, H.; Duffy, S.; Shaw, J.; Walton, A.; Farrington, C.; Gunaratne, R.; Broughton, A.; Federman, J.; Keighley, C.; Dart, A.; Clark, D.; Johns, J.; Horrigan, M.; Farouque, O.; Oliver, L.; Brennan, J.; Chan, R.; Proimos, G.; Dortimer, T.; Chan, B.; Tonkin, A.; Brown, L.; Champbell, N.; Sahar, A.; Charter, K.; New, G.; Roberts, L.; Liew, H.; Rowe, M.; Proimos, G.; Cheong, N.; Goods, C.; Lew, R.; Szto, G.; Templin, R.; Black, A.; Sebastian, M.; Yip, T.; Ponnuthrai, L.; Rahmen, M.; Dyson, J.; Duplessis, T.; Krum, H.; Reid, C.; Brennan, A.; Meehan, A.; Loane, P.; Curran, L.; Groen, F.; Szto, G.; O'Shea, V.; Ajani, A.; Warren, R.; Eccleston, D.; Lefkovits, J.; Yan, B.; Roy, P.; Shetty, S.; Gurvitch, R.; Lim, Y.; Eccleston, D.; Walton, A. (2009)Background: Ostial lesions are a difficult subset associated with suboptimal outcomes after percutaneous coronary intervention (PCI). The aim of this study was to analyze outcomes of ostial lesions in contemporary Australian ...
Zhu, Y.; Hayward, P.; Hare, D.; Reid, Christopher; Stewart, A.; Buxton, B. (2013)OBJECTIVES: We evaluated the influence of lipid exposure upon conduit patency in long-term follow-up after primary CABG. METHODS: From a prospectively compiled database, we identified 1207 grafts (436 SV and 771 mixed ...