title: Atorvastatin and fenofibrate combination induces the predominance of the large HDL subclasses and increased apo AI fractional catabolic rates in New Zealand white rabbits with exogenous hypercholesterolemia.
abstract: The anti-atherogenic properties of high-density lipoproteins (HDLs) may be related to their structure and metabolism. The HDL physicochemical characteristics that determine their plasma clearance during treatment with statins and fibrates are not well understood. In this study, we analyzed HDL-apo AI fractional catabolic rates (FCRs), size distributions, and the lipid composition of the HDL subclasses in New Zealand white rabbits with exogenous dyslipidemia that received low doses of atorvastatin and fenofibrate. Hypercholesterolemia decreased only partially with the combination of both drugs. HDL size distribution shifted toward larger particles among the groups of rabbits that received atorvastatin, fenofibrate, or their combination, compared with both the control group and the dyslipidemic group. The HDL subclasses were significantly rich in cholesterol in each of the groups compared with controls. The structural changes noted in the HDL subclasses were not associated with impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy and the drug combination group were all associated with a higher apo AI FCR value compared with both the dyslipidemic rabbits and the control group. In conclusion, the combination of atorvastatin and fenofibrate induced a more favorable HDL subclass profile than did the individual use of these drugs. Similarly, the apo AI FCR values were augmented in every group receiving drug treatment (either monotherapy or combination therapy) in the setting of hypercholesterolemia. The anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may be enhanced by the structural and metabolic modifications induced by the combination of atorvastatin and fenofibrate.
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Cristobal
authors.initials: C
authors.lastname: Flores-Castillo
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Juan Á
authors.initials: JÁ
authors.lastname: Zamora-Pérez
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.|Study Group of Atherosclerosis, Instituto Nacional de Cardiología 'Ignacio Chávez', México City, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Carreón-Torres
authors.affiliation: Biosen Institut, Legaria 779-301, Col. Irrigación, 11500 Mexico City, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Arzola-Paniagua
authors.affiliation: Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga 15, 14080, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Aguilar-Salinas
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Victoria
authors.initials: V
authors.lastname: López-Olmos
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.|Study Group of Atherosclerosis, Instituto Nacional de Cardiología 'Ignacio Chávez', México City, Mexico.
authors.forename: José M
authors.initials: JM
authors.lastname: Fragoso
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.
authors.forename: María
authors.initials: M
authors.lastname: Luna-Luna
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.
authors.forename: José M
authors.initials: JM
authors.lastname: Rodríguez-Pérez
authors.affiliation: Study Group of Atherosclerosis, Instituto Nacional de Cardiología 'Ignacio Chávez', México City, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.|Study Group of Atherosclerosis, Instituto Nacional de Cardiología 'Ignacio Chávez', México City, Mexico.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología 'Ignacio Chávez' Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico.|Study Group of Atherosclerosis, Instituto Nacional de Cardiología 'Ignacio Chávez', México City, Mexico.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Pérez-Méndez
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D004357:Drug Synergism; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008297:Male; D011817:Rabbits
chemical_list: D016632:Apolipoprotein A-I; D001786:Blood Glucose; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D000069059:Atorvastatin; D043303:Aryldialkylphosphatase; D011345:Fenofibrate
keywords: PPARalpha; apo AI catabolism; fibrates; reverse cholesterol transport; statins