Identificación de marcadores de inmunosenescencia en modelos de enfermedad cardiovascular, infección y enfermedades con base inflamatoria

• Autores: Pablo Álvarez Heredia
• Directores de la Tesis: Alejandra Pera Rojas (dir. tes.)
• Lectura: En la Universidad de Córdoba (ESP) ( España ) en 2024
• Idioma: español
• Tribunal Calificador de la Tesis: Ernesto Mejías Pérez (presid.), Javier García Casado (secret.), Anna Aiello (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad de Córdoba
• Materias:
  • Ciencias médicas
    • Patología
      • Patología cardiovascular
• Enlaces
  • Tesis en acceso abierto en: Helvia
• Resumen

  • 1. Introducción o motivación de la tesis: El sistema inmunitario es un complejo sistema de defensa que protege al organismo de amenazas. La inmunosenescencia es el deterioro del sistema inmunitario relacionado con el envejecimiento, caracterizado por la acumulación de células T memoria y por la disminución de la subpoblación de células T vírgenes (involución del timo). Este desequilibrio contribuye a una mayor susceptibilidad a infecciones y una reducción de la respuesta inmunitaria con el tiempo. El citomegalovirus humano (HCMV) es un patógeno que causa una infección crónica en el huésped y ha sido identificado como un promotor clave del proceso de inmunosenescencia. No obstante, a pesar de su elevada prevalencia e impacto en la salud, todavía no existe tratamiento o prevención para reducir o controlar el impacto del HCMV. Así, el estudio de sus efectos sobre el sistema inmunitario, y de su papel como promotor de diversas patologías asociadas a la edad, es imprescindible para el desarrollo de nuevas estrategias que permitan reducir los efectos negativos de este virus sobre nuestra salud.

    2.Contenido de la investigación: En este trabajo se ha realizado una evaluación de la contribución del HCMV como factor de riesgo cardiovascular. Para ello, se desarrolló un protocolo que nos ha permitido el estudio de las poblaciones inmunitarias infiltrantes de tejido cardiovascular mediante citometría de flujo. Además, evaluamos los efectos a medio y largo plazo de la coinfección por HCMV y SARS-CoV-2 sobre el sistema inmunitario como factor de riesgo cardiovascular. Por último, se realizó un estudio sobre la seroprevalencia actual del HCMV en la población española.

    3.Conclusión: Este estudio nos ha permitido evaluar por primera vez la variación en la seroprevalencia de este virus durante las dos primeras décadas del siglo XXI, tras 30 años desde su última evaluación en España. La aplicación de nuestro novedoso protocolo en el estudio de la estenosis aórtica ha posibilitado por primera vez el estudio detallado a nivel fenotípico y funcional de células infiltrantes aisladas del tejido de la válvula aórtica calcificada. Así mismo, nuestros resultados han permitido evaluar el nivel de inmunosenescencia de estas poblaciones celulares, abriendo la puerta al estudio de otras enfermedades cardiovasculares mediante citometría de flujo. Además, el análisis de marcadores de inmunosenescencia en pacientes COVID-19 no hospitalizados ha revelado una senescencia acelerada de las células T en individuos HCMV-seropositivos similar a la que presentan los pacientes de estenosis aórtica. Estos hallazgos revelan el potencial peligro que supone la infección crónica por HCMV para nuestra salud, aumentando el riesgo de padecer enfermedades asociadas a la edad, como la enfermedad cardiovascular. Por último, al tratar de extrapolar el impacto de la coinfección del HCMV y el SARS-CoV-2 a la población española se halló una ausencia de estudios de este tipo desde 1993. Los resultados de nuestro estudio sugieren que la seroprevalencia española del HCMV se ha mantenido sin cambios durante la última década del siglo XXI. Sin embargo, observamos un aumento de 1,4 veces en la presencia del virus en mujeres en edad fértil (18-40 años) en los últimos 10 años, lo que sugiere un aumento del riesgo de infección congénita por HCMV.

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