HDL (High-Density Lipoprotein) Remodeling and Magnetic Resonance Imaging-Assessed Atherosclerotic Plaque Burden: Study in a Preclinical Experimental Model
Por:
Ben-Aicha S., Casaní L., Muñoz-Garciá N., Joan-Babot O., Peña E., Aržanauskaite M., Gutierrez M., Mendieta G., Padró T., Badimon L., Vilahur G.
Publicada:
1 oct 2020
Ahead of Print:
1 ene 2020
Resumen:
Objective: HDL (high-density lipoprotein) role in atherosclerosis is controversial. Clinical trials with CETP (cholesterylester transfer protein)-inhibitors have not provided benefit. We have shown that HDL remodeling in hypercholesterolemia reduces HDL cardioprotective potential. We aimed to assess whether hypercholesterolemia affects HDL-induced atherosclerotic plaque regression. Approach and Results: Atherosclerosis was induced in New Zealand White rabbits for 3-months by combining a high-fat-diet and double-balloon aortic denudation. Then, animals underwent magnetic resonance imaging (basal plaque) and randomized to receive 4 IV infusions (1 infusion/wk) of HDL isolated from normocholesterolemic (NC-HDL; 75 mg/kg; n=10), hypercholesterolemic (HC-HDL; 75 mg/Kg; n=10), or vehicle (n=10) rabbits. Then, animals underwent a second magnetic resonance imaging (end plaque). Blood, aorta, and liver samples were obtained for analyses. Follow-up magnetic resonance imaging revealed that NC-HDL administration regressed atherosclerotic lesions by 4.3%, whereas, conversely, the administration of HC-HDLs induced a further 6.5% progression (P<0.05 versus basal). Plaque characterization showed that HC-HDL administered animals had a 2-fold higher lipid and cholesterol content versus those infused NC-HDL and vehicle (P<0.05). No differences were observed among groups in CD31 levels, nor in infiltrated macrophages or smooth muscle cells. Plaques from HC-HDL administered animals exhibited higher Casp3 (caspase 3) content (P<0.05 versus vehicle and NC-HDL) whereas plaques from NC-HDL infused animals showed lower expression of Casp3, Cox1 (cyclooxygenase 1), inducible nitric oxide synthase, and MMP (metalloproteinase) activity (P<0.05 versus HC-HDL and vehicle). HDLs isolated from animals administered HC-HDL displayed lower antioxidant potential and cholesterol efflux capacity as compared with HDLs isolated from NC-HDL-infused animal and vehicle or donor HDL (P<0.05). There were no differences in HDL-ApoA1 content, ABCA1 (ATP-binding cassette transporter A1) vascular expression, and SRB1 (scavenger receptor B1) and ABCA1 liver expression. Conclusions: HDL particles isolated from a hypercholesterolemic milieu lose their ability to regress and stabilize atherosclerotic lesions. Our data suggest that HDL remodeling in patients with co-morbidities may lead to the loss of HDL atheroprotective functions. © 2020 S. Karger AG. All rights reserved.
Filiaciones:
Ben-Aicha S.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
School of Medicine, University of Barcelona (UB), Spain
Casaní L.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Muñoz-Garciá N.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Joan-Babot O.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Peña E.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain
Aržanauskaite M.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Gutierrez M.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Cardiology Department, Hospital Clinico Barcelona Spain, Spain
Mendieta G.:
School of Medicine, University of Barcelona (UB), Spain
Padró T.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain
Badimon L.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain
Cardiovascular Research Chair, Universidad Autónoma Barcelona (UAB), Spain
Vilahur G.:
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain
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