Influencia de los anticuerpos anti-LDL oxidada y del control glucémico sobre diferentes rutas metabólicas implicadas en la aterogénesis en pacientes con enfermedad arterial periférica y diabetes tipo 2

• Autores: Victor Gomez-Carrillo
• Directores de la Tesis: Ricardo Gómez Huelgas (dir. tes.), M. Rosa Bernal Lopez (codir. tes.)
• Lectura: En la Universidad de Málaga ( España ) en 2017
• Idioma: español
• Tribunal Calificador de la Tesis: Raúl J. Andrade Bellido (presid.), María M. Malagón Poyato (secret.), Francisco Javier Carrasco Sánchez (voc.)
• Materias:
  • Ciencias de la vida
    • Fisiología humana
      • Metabolismo humano
    • Inmunología
      • Anticuerpos
  • Ciencias médicas
    • Medicina interna
      • Endocrinología
    • Patología
      • Arterioesclerosis
• Enlaces
  • Tesis en acceso abierto en: RIUMA
• Resumen

  • Influencia de los anticuerpos anti-LDL oxidada y del control glucémico sobre diferentes rutas metabólicas implicadas en la aterogénesis en pacientes con enfermedad arterial periférica y diabetes tipo 2.

    OBJETIVOS:

    1. Estudiar la expresión génica de diferentes biomarcadores implicados en el proceso aterogénico (apoptosis, inflamación, metabolismo lipídico) en muestras de arteria poplítea ocluida y de arteria mamaria en pacientes con diabetes tipo 2.

    2. Estudiar la influencia del control glucémico en la expresión génica de diferentes biomarcadores implicados en el proceso aterogénico (apoptosis, inflamación, metabolismo lipídico) en muestras de arteria poplítea ocluida en pacientes con diabetes tipo 2.

    3. Analizar la correlación entre los niveles plasmáticos de anticuerpos anti-LDL oxidada IgG e IgM y la expresión génica de diversos biomarcadores implicados en el proceso aterogénico (apoptosis, inflamación, metabolismo lipídico) en muestras de arteria poplítea ocluida en pacientes con diabetes tipo 2.

    MATERIAL-MÉTODOS Y RESULTADOS:

    El estudio incluyó a 20 individuos con DM2 establecida, 5 pacientes con cardiopatía isquémica que fueron sometidos a bypass coronario, presentando un buen control glucémico (HbA1c <6,5%) antes de la intervención. De estos sujetos fueron obtenidas las arterias controles libres de ateroma como la arteria mamaria interna (AMI). Por otro lado, fueron reclutados 15 pacientes que presentaban enfermedad arterial periférica (EAP) grave por lo que fueron sometidos a amputación supracondílea de miembros inferiores, obteniéndose del mismo paciente el paquete vascular compuesto de arteria poplítea ocluida (APO) y vena femoral (VF). Estos pacientes fueron clasificados en función de su HbA1c, considerando buen control (HbA1c ≤ 6,5) y mal control (HbA1c > 6,5).

    Se realizó un estudio histológico y análisis de expresión génica y proteica, en las diferentes muestras de AMI, APO y VF. Tras el análisis de 46 genes, APO mostró niveles de expresión más altos que AMI o VF en cuanto a genes implicados en la trombosis (FT), la apoptosis (MMP2, MMP9, TIMP1 y TIMP3), metabolismo lipídico (LRP1 y NDUFA), la respuesta inmune (TLR2).

    Si clasificamos a los pacientes considerando su HbA1c, en la APO, sólo MMP9 mostró un incremento en su expresión en pacientes con un mal control glucémicos frente a pacientes diabéticos con buen control (p=<0.0001).

    Por otro lado fue estudiada la posible relación entre los niveles plasmáticos de anticuerpos IgG/IgM anti–LDL oxidada (obtenido mediante ELISA) y los diferentes biomarcadores involucrados en las distintas rutas metabólicas ya que la partícula de LDL oxidada se considera la forma más aterogénica del LDL y por tanto tiene una fuerte implicación en la formación de la placa ateromatosa.

    Cuando fueron analizadas las biopsias de APO, solamente los anticuerpos IgM anti – LDL oxidada mostraron una correlación positiva con varios biomarcadores implicados en inflamación (VEGFA), apoptosis (AKT1, BAX, CDKN1A, MMP10) y metabolismo lipídico (SCARB1). Sin embargo, los anticuerpos IgG anti-LDL oxidada no tuvieron correlación con ninguno de los biomarcadores estudiados CONCLUSIONES:

    1. Las arterias poplíteas ocluidas de pacientes con diabetes tipo 2, en comparación con las arterias mamarias libres de ateroesclerosis, presentan una alta expresión de biomarcadores de apoptosis, de inflamación y de metabolismo lipídico.

    2. El mal control glucémico no modifica la expresión génica de diferentes biomarcadores proateroscleróticos (apoptosis, inflamación, metabolismo lipídico) en las arterias poplíteas ocluidas de pacientes con diabetes tipo 2.

    3. Existe una correlación positiva entre los niveles plasmáticos de anticuerpos anti-LDL oxidada IgM y la expresión génica de diferentes biomarcadores implicados en la aterogénesis (apoptosis, inflamación, metabolismo lipídico) en las arterias poplíteas ocluidas de pacientes con diabetes tipo 2.

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