Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas

Patients with chronic kidney disease (CKD) on hemodialysis have a markedly elevated rate of cardiovascular mortality, among 10 and 20 fold higher related to the general population. Their cardiometabolic feature usually presents paradoxical situations that do not explain the increased incidence of ca...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor principal: Cacciagiú, Leonardo Damián
Otros Autores: González, Ana Inés
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2016
Materias:
Enfermedad renal crónica
Lipoproteína
Factores proinflamatorios
Aterosclerosis
Ciencia de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1452
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1452.dir/1452.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-HWA_1452
record_format dspace
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic Enfermedad renal crónica
Lipoproteína
Factores proinflamatorios
Aterosclerosis
Ciencia de la vida
spellingShingle Enfermedad renal crónica
Lipoproteína
Factores proinflamatorios
Aterosclerosis
Ciencia de la vida
Cacciagiú, Leonardo Damián
Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
topic_facet Enfermedad renal crónica
Lipoproteína
Factores proinflamatorios
Aterosclerosis
Ciencia de la vida
description Patients with chronic kidney disease (CKD) on hemodialysis have a markedly elevated rate of cardiovascular mortality, among 10 and 20 fold higher related to the general population. Their cardiometabolic feature usually presents paradoxical situations that do not explain the increased incidence of cardiovascular events.\nWe evaluated parameters related to lipid-lipoprotein profile, pro-inflammatory status and constituents of arterial wall by an observational, descriptive and cross-sectional design. We also carried out three in vitro experimental tests to evaluate lipoproteins functionality of and explain cytokines alterations. We included CKD patients on hemodialysis (n = 120) and healthy controls (n = 56).\nWe observed a moderate hypertriglyceridemia reflected in a accumulation of remnants lipoprotein, which was scarcely studied in this condition. VLDL were small with higher cholesterol, and had lower affinity for the enzyme that degrades it. The accumulation of triglyceride-rich lipoproteins is attributed to catabolism deficit. The decrease in LDL is paradoxical and is associated with risk of cardiovascular events, responding to curves U-shape. LDL presented qualitative alterations that increase their atherogenicity. HDL were dysfunctional and presented lower antioxidant capacity associated with lower paraoxonase activity, in addition to changes in its composition.\nAn increase in interleukin-6 and hs-CRP evidenced a subclinical inflammation, which was promoted, in part, by atherogenic lipoproteins. Adiponectin presented, paradoxically, higher values that would not exhert its anti-inflammatory role. This increase is due to decreased renal elimination, since we did not observe adiponectina expression increased in adipose tissue of rats with renal failure.\nThe factors related to the arterial wall, demonstrated, in CKD, impaired arterial function evidenced by endothelin-1 increase, phospholipase A2 activity with pro-oxidant action increase and elevated metalloproteinase-2 and -9, whole related to an active process remodeling and vulnerability of atheromatous plaques.\nThe interrelationship of these cardiometabolic parameters, several of them studied for the first time, allows us to deduce a sequence of steps that explain the accelerated atherosclerosis in CKD on hemodialysis.
author2 González, Ana Inés
author_facet González, Ana Inés
Cacciagiú, Leonardo Damián
format Tesis doctoral
Tesis doctoral
acceptedVersion
author Cacciagiú, Leonardo Damián
author_sort Cacciagiú, Leonardo Damián
title Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
title_short Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
title_full Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
title_fullStr Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
title_full_unstemmed Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
title_sort lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas
publisher Facultad de Farmacia y Bioquímica
publishDate 2016
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1452
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1452.dir/1452.PDF
work_keys_str_mv AT cacciagiuleonardodamian lipoproteinasaterogenicasfactoresproinflamatoriosyvascularesenlaenfermedadrenalcronicasituacionesparadojicas
_version_ 1766017475569254400
spelling I28-R145-HWA_14522019-09-25 Patients with chronic kidney disease (CKD) on hemodialysis have a markedly elevated rate of cardiovascular mortality, among 10 and 20 fold higher related to the general population. Their cardiometabolic feature usually presents paradoxical situations that do not explain the increased incidence of cardiovascular events.\nWe evaluated parameters related to lipid-lipoprotein profile, pro-inflammatory status and constituents of arterial wall by an observational, descriptive and cross-sectional design. We also carried out three in vitro experimental tests to evaluate lipoproteins functionality of and explain cytokines alterations. We included CKD patients on hemodialysis (n = 120) and healthy controls (n = 56).\nWe observed a moderate hypertriglyceridemia reflected in a accumulation of remnants lipoprotein, which was scarcely studied in this condition. VLDL were small with higher cholesterol, and had lower affinity for the enzyme that degrades it. The accumulation of triglyceride-rich lipoproteins is attributed to catabolism deficit. The decrease in LDL is paradoxical and is associated with risk of cardiovascular events, responding to curves U-shape. LDL presented qualitative alterations that increase their atherogenicity. HDL were dysfunctional and presented lower antioxidant capacity associated with lower paraoxonase activity, in addition to changes in its composition.\nAn increase in interleukin-6 and hs-CRP evidenced a subclinical inflammation, which was promoted, in part, by atherogenic lipoproteins. Adiponectin presented, paradoxically, higher values that would not exhert its anti-inflammatory role. This increase is due to decreased renal elimination, since we did not observe adiponectina expression increased in adipose tissue of rats with renal failure.\nThe factors related to the arterial wall, demonstrated, in CKD, impaired arterial function evidenced by endothelin-1 increase, phospholipase A2 activity with pro-oxidant action increase and elevated metalloproteinase-2 and -9, whole related to an active process remodeling and vulnerability of atheromatous plaques.\nThe interrelationship of these cardiometabolic parameters, several of them studied for the first time, allows us to deduce a sequence of steps that explain the accelerated atherosclerosis in CKD on hemodialysis. Fil: Cacciagiú, Leonardo Damián. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina González, Ana Inés Facultad de Farmacia y Bioquímica Schreier, Laura Cacciagiú, Leonardo Damián 2016-05-05 Los pacientes con enfermedad renal crónica (ERC) en hemodiálisis presentan una tasa de mortalidad cardiovascular marcadamente elevada, entre 10 y 20 veces superior a la de la población general. Su cuadro cardiometabólico suele presentar situaciones paradójicas que no explican la incrementada incidencia de eventos cardiovasculares.\nMediante un diseño observacional, descriptivo y transversal se evaluaron parámetros circulantes correspondientes al perfil lipídico-lipoproteico, cuadro pro-inflamatorio y constituyentes de pared arterial, y además se llevaron a cabo de tres ensayos experimentales in vitro para evaluar funcionalidad de lipoproteínas y explicar alteraciones de citoquinas. Se incluyeron pacientes con ERC en hemodiálisis (n=120) y controles sanos (n=56).\nSe observó una hipertrigliceridemia moderada reflejada en la acumulación de remanentes lipoproteicos, muy poco estudiado previamente en esta condición. Las VLDL fueron pequeñas y ricas en colesterol, y presentaron menor afinidad con la enzima que la degrada. La acumulación de las lipoproteínas ricas en triglicéridos se atribuye al déficit del catabolismo. La disminución de col-LDL es paradójica y constituye un marcado riesgo de eventos cardiovasculares, respondiendo a curvas de relación de forma-U. LDL presentó alteraciones cualitativas que incrementan su aterogenicidad. HDL fue disfuncional con menor capacidad anti-oxidante sobre LDL, asociado a menor actividad de paraoxonasa, además de alteraciones en su composición. \nLa inflamación subclínica quedó evidenciada por el marcado incremento de interleuquina-6 y PCR-us, promovidos en parte por las lipoproteínas aterogénicas. Adiponectina presentó, paradójicamente, valores más elevados, que no cumplirían su rol anti-inflamatorio. Este aumento se debería a una disminución de su eliminación renal, ya que no se observó incremento de su expresión en ratas con insuficiencia renal.\nLos factores relacionados con la pared arterial, demostraron en ERC, alteración de la función arterial evidenciado por aumento de endotelina-1, actividad de fosfolipasa A2 con acción pro-oxidante e incremento de metaloproteasa-2 y -9, relacionado a un proceso activo de remodelamiento y vulnerabilidad de las placas ateromatosas. \nLa interrelación de estos parámetros cardiometabólicos, varios de ellos estudiados por primera vez, permiten deducir una secuencia de pasos que explican la ateroesclerosis acelerada en la ERC en hemodiálisis. application/pdf Angerosa, Margarita Chicco, Adriana Lucentini, Marcelo Enfermedad renal crónica Lipoproteína Factores proinflamatorios Aterosclerosis spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencia de la vida Lipoproteínas aterogénicas, factores proinflamatorios y vasculares en la enfermedad renal crónica : situaciones paradójicas info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1452 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1452.dir/1452.PDF

Ejemplares similares